TY - JOUR
AU - Ohe,, Yuichiro
AB - Abstract The Japan Clinical Oncology Group Lung Cancer Study Group has been carrying out clinical studies, exploring new strategies of treatment, supportive therapies (antiemetics, etc.), etc., for a variety of cancers, including not only small cell lung cancer and non-small cell lung cancer but also rare chest tumours (represented by thymoma) and cancer-associated conditions (cancerous pericarditis, cancerous pleuritis, etc.). In this review, an overview of all studies conducted from 1985 to 2019 is provided. Japan Clinical Oncology Group (JCOG), Lung Cancer Study Group (LCSG), small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC) Beginning of the Japan Clinical Oncology Group Lung Cancer Study Group The Japan Clinical Oncology Group (JCOG) Lung Cancer Study Group was established from a multicenter phase III trial in patients with small cell lung cancer (SCLC) carried out by the ‘Multidisciplinary Cancer Treatment Research’ Group (Chief Researcher: Keiichi Suemasu) within the framework of the specific cancer research program started in 1978 with financial aid from the Ministry of Health and Welfare. The group was constituted in 1982 and the phase III trial mentioned above was later named the JCOG8502 study (1). The ‘Multidisciplinary Cancer Treatment Research’ Group was succeeded in 1987 by the ‘Multidisciplinary Solid Cancer Treatment Research’ Group (Chief Researcher: Masanori Yamashita), and the JCOG was constituted in 1990. Thereafter, Dr. Saijo, Dr. Tamura and Dr. Ohe served as group chairs (Table 1). Table 1 Group chairs and coordinators . Group chairs . Group coordinators . April 1978 to December 1985 Nagahiro Saijo — January 1986 to May 2002 Nagahiro Saijo Tomohide Tamura June 2002 to June 2009 Tomohide Tamura Tomohide Tamura July 2009 to March 2014 Tomohide Tamura Noboru Yamamoto April 2014 to September 2016 Yuichiro Ohe Noboru Yamamoto October 2016 to date Yuichiro Ohe Hidehito Horinouchi . Group chairs . Group coordinators . April 1978 to December 1985 Nagahiro Saijo — January 1986 to May 2002 Nagahiro Saijo Tomohide Tamura June 2002 to June 2009 Tomohide Tamura Tomohide Tamura July 2009 to March 2014 Tomohide Tamura Noboru Yamamoto April 2014 to September 2016 Yuichiro Ohe Noboru Yamamoto October 2016 to date Yuichiro Ohe Hidehito Horinouchi Open in new tab Table 1 Group chairs and coordinators . Group chairs . Group coordinators . April 1978 to December 1985 Nagahiro Saijo — January 1986 to May 2002 Nagahiro Saijo Tomohide Tamura June 2002 to June 2009 Tomohide Tamura Tomohide Tamura July 2009 to March 2014 Tomohide Tamura Noboru Yamamoto April 2014 to September 2016 Yuichiro Ohe Noboru Yamamoto October 2016 to date Yuichiro Ohe Hidehito Horinouchi . Group chairs . Group coordinators . April 1978 to December 1985 Nagahiro Saijo — January 1986 to May 2002 Nagahiro Saijo Tomohide Tamura June 2002 to June 2009 Tomohide Tamura Tomohide Tamura July 2009 to March 2014 Tomohide Tamura Noboru Yamamoto April 2014 to September 2016 Yuichiro Ohe Noboru Yamamoto October 2016 to date Yuichiro Ohe Hidehito Horinouchi Open in new tab The JCOG8502 study was carried out with the participation of five facilities, including the National Cancer Center Hospital, the National Matsudo Hospital (currently the National Cancer Center Hospital East), the Osaka Prefectural Habikino Hospital (currently the Osaka Habikino Medical Center), the National Kinki-chuo Hospital (currently the Kinki-chuo Chest Medical Center) and the Osaka Adult Disease Center (Currently the Osaka International Cancer Institute) (1). In those days, no data centers were available, and researchers had to control and analyze the data by themselves. The JCOG8502 study is the first large-scale investigator-initiated phase III clinical trial for lung cancer in Japan (1). Following success in this trial, many facilities joined the JCOG, thus establishing the base for the JCOG Lung Cancer Study Group. Development of treatment strategies for SCLC The first study on SCLC for which a JCOG number was assigned was a randomized study designed to compare CAV (cyclophosphamide 800 mg/m2, Day 1 + doxorubicin 50 mg/m2, Day 1 + vincristine 1.4 mg/m2, Day 1) therapy, which initially served as the standard therapy, PE (cisplatin [CDDP] 80 mg/m2, Day 1 + etoposide [VP-16] 100 mg/m2, Days 1, 3 and 5) therapy and CAV/PE therapy, in which CAV therapy and PE therapy are adopted in alternating fashion (Table 2). In this study, which involved 300 patients, the median survival time tended to be slightly longer in the CAV/PE therapy group than that in the other two groups (11.8 vs. 9.9 months in each of the other two groups), but the difference was rated as not ‘dramatic’ (1). The subsequently performed JCOG9106 study was a phase III trial designed to compare CODE therapy (CDDP 25 mg/m2 administered weekly for 9 weeks + vincristine 1 mg/m2 administered in weeks 1, 2, 4 and 6 + doxorubicin 40 mg/m2 + VP-16 80 mg/m2 administered for 3 days each in weeks 1, 3, 5 and 7 + G-CSF (granulocyte colony stimulating factor) administered on consecutive days except on the days of administration of the chemotherapeutic agents) with the above-mentioned CAV/PE therapy (5). The median survival time did not differ significantly between the CODE therapy (test therapy) group (11.6 months) and the CAV/PE therapy group (10.9 months). Irinotecan was clinically introduced as a key drug for SCLC after VP-16, and a phase III trial (JCOG9511 study) comparing CDDP + VP-16 therapy with CDDP + irinotecan therapy was carried out (8). This well-known trial was initially planned with the target study sample size set at 230 subjects. However, the study was discontinued prematurely even after 154 subjects were registered, because CDDP + irinotecan therapy was shown to be effective by that time (median survival time 12.8 vs. 9.4 months), with the therapy subsequently serving as the standard therapy in Japan (8). Of note, the salvage irinotecan treatment was not permitted after disease progression in cisplatin + VP-16 arm in this trial. Table 2 Development of treatment strategies for small cell lung cancer JCOG No. . Phase, etc. . Study outline . Results . Reference . 8502 Phase III Randomized trial of cyclophosphamide, doxorubicin and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer The median survival time was 9.9 months with CAV, 9.9 months with PE, and 11.8 months with CAV/PE (1) 8803 Phase II Concurrent cisplatin-etoposide chemotherapy plus thoracic radiotherapy for limited-stage small cell lung cancer CDDP + VP-16 therapy combined with chest radiation resulted in a median survival time of 14.8 months and a 2-year survival rate of 20% (2) 8809 Phase I/II A study of dose escalation of teniposide (VM-26) plus cisplatin (CDDP) with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in patients with advanced small cell lung cancer Teniposide 100 mg/m2/day for 5 days was determined to be the recommended dose level/duration for teniposide (3) 9104 Phase III Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer Survival was better with concurrent chemotherapy + radiotherapy than with sequential chemotherapy + radiotherapy (4) 9106 Phase III Phase III study of intensive weekly chemotherapy with recombinant human granulocyte colony-stimulating factor versus standard chemotherapy in extensive-disease small-cell lung cancer No superiority of the test therapy (CODE therapy) over CAV/PE therapy was demonstrated (5) 9111 Phase II Cisplatin plus oral etoposide in the treatment of patients with advanced small cell lung cancer Long-term oral VP-16 therapy was effective, but was associated with prolonged gastrointestinal toxicity (6) 9409 Phase II Phase II study of area under the plasma-concentration-versus-time curve-based carboplatin plus standard-dose intravenous etoposide in elderly patients with small-cell lung cancer A phase III trial of CBDCA + VP-16 for elderly patients was judged as being warranted (7) 9509 Phase II A phase II study of concurrent cisplatin/etoposide (PE) and twice-daily thoracic radiotherapy (BID TRT) followed by weekly dose intensive regimen (CODE) with human granulocyte-colony stimulating factor (G-CSF) for limited stage (LS) small cell lung cancer (SCLC) The study was discontinued prematurely because evidence for the better treatment outcomes of twice-daily irradiation was established during the study (which involved only once-daily irradiation) and because the planned duration of CODE therapy was long 9511 Phase III Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer Superiority of CDDP + irinotecan therapy over CDDP + VP-16 therapy was demonstrated (8) 9702 Phase I/II Randomized phase III trial of carboplatin plus etoposide vs. split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer Although no superiority of CBDCA + VP-16 therapy over CDDP + VP-16 therapy was demonstrated, the CBDCA + VP16 regimen was judged as being a useful additional alternative for treatment (9) 9902DI Phase II Randomized phase II study of cisplatin, irinotecan and etoposide combinations administered weekly or every 4 weeks for extensive small-cell lung cancer On the basis of the response rate, the 4-week dosing regimen was judged as being suitable as the test therapy for the phase III trial (10) 9903DI Phase II Pilot study of concurrent etoposide and cisplatin plus accelerated hyperfractionated thoracic radiotherapy followed by irinotecan and cisplatin for limited-stage small cell lung cancer Safety of CDDP + irinotecan therapy following combined CDDP + VP-16 and radiation therapy was demonstrated, and it was decided that this therapy would be used in the JCOG0202 study (11) 0101DI Phase II A phase II study of weekly taxol chemotherapy for platinum refractory small cell lung cancer 0202 Phase III A phase III study comparing etoposide and cisplatin (EP) with irinotecan and cisplatin (IP) following EP plus concurrent accelerated hyperfractionated thoracic irradiation (EP/TRT) for the treatment of limited-stage small-cell lung cancer No superiority of CDDP + irinotecan therapy was demonstrated (12) 0509 Phase III A phase III randomized, multicenter study comparing irinotecan and cisplatin (IP) with amrubicin and cisplatin (AP) for the treatment of extensive-stage small-cell lung cancer No superiority of CDDP + amrubicin therapy was demonstrated (13) 0605 Phase III A phase III study comparing irinotecan, cisplatin and etoposide (PEI) with nogitecan for the treatment of relapsed small-cell lung cancer Superiority of PEI therapy was demonstrated (14) 0901 Phase II Phase II study of amrubicin in patients with small-cell lung cancer that is refractory or relapsed within 90 days of completing previous treatment Effectiveness of amrubicin was demonstrated (15) 1011 Phase II Randomized phase II trial of CODE or amrubicin and cisplatin chemotherapy following concurrent cisplatin, etoposide and accelerated hyperfractionation thoracic radiotherapy for limited disease small cell lung cancer Neither group showed the 1-year aggravation-free survival rate expected for advancement to evaluation of the test treatment by a phase III trial (16) 1201 Phase II/III A phase II/III study comparing carboplatin and irinotecan (CI) with carboplatin and etoposide (CE) for the treatment of elderly extended-stage small-cell lung cancer (JCOG1201, elderly ED-SCLC/CI vs. CE) Follow-up after completion of enrollment 1205/1206 Phase III A phase III study comparing irinotecan and cisplatin with etoposide and cisplatin for adjuvant chemotherapy of completely resected pulmonary high-grade neuroendocrine carcinoma Follow-up after completion of enrollment JCOG No. . Phase, etc. . Study outline . Results . Reference . 8502 Phase III Randomized trial of cyclophosphamide, doxorubicin and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer The median survival time was 9.9 months with CAV, 9.9 months with PE, and 11.8 months with CAV/PE (1) 8803 Phase II Concurrent cisplatin-etoposide chemotherapy plus thoracic radiotherapy for limited-stage small cell lung cancer CDDP + VP-16 therapy combined with chest radiation resulted in a median survival time of 14.8 months and a 2-year survival rate of 20% (2) 8809 Phase I/II A study of dose escalation of teniposide (VM-26) plus cisplatin (CDDP) with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in patients with advanced small cell lung cancer Teniposide 100 mg/m2/day for 5 days was determined to be the recommended dose level/duration for teniposide (3) 9104 Phase III Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer Survival was better with concurrent chemotherapy + radiotherapy than with sequential chemotherapy + radiotherapy (4) 9106 Phase III Phase III study of intensive weekly chemotherapy with recombinant human granulocyte colony-stimulating factor versus standard chemotherapy in extensive-disease small-cell lung cancer No superiority of the test therapy (CODE therapy) over CAV/PE therapy was demonstrated (5) 9111 Phase II Cisplatin plus oral etoposide in the treatment of patients with advanced small cell lung cancer Long-term oral VP-16 therapy was effective, but was associated with prolonged gastrointestinal toxicity (6) 9409 Phase II Phase II study of area under the plasma-concentration-versus-time curve-based carboplatin plus standard-dose intravenous etoposide in elderly patients with small-cell lung cancer A phase III trial of CBDCA + VP-16 for elderly patients was judged as being warranted (7) 9509 Phase II A phase II study of concurrent cisplatin/etoposide (PE) and twice-daily thoracic radiotherapy (BID TRT) followed by weekly dose intensive regimen (CODE) with human granulocyte-colony stimulating factor (G-CSF) for limited stage (LS) small cell lung cancer (SCLC) The study was discontinued prematurely because evidence for the better treatment outcomes of twice-daily irradiation was established during the study (which involved only once-daily irradiation) and because the planned duration of CODE therapy was long 9511 Phase III Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer Superiority of CDDP + irinotecan therapy over CDDP + VP-16 therapy was demonstrated (8) 9702 Phase I/II Randomized phase III trial of carboplatin plus etoposide vs. split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer Although no superiority of CBDCA + VP-16 therapy over CDDP + VP-16 therapy was demonstrated, the CBDCA + VP16 regimen was judged as being a useful additional alternative for treatment (9) 9902DI Phase II Randomized phase II study of cisplatin, irinotecan and etoposide combinations administered weekly or every 4 weeks for extensive small-cell lung cancer On the basis of the response rate, the 4-week dosing regimen was judged as being suitable as the test therapy for the phase III trial (10) 9903DI Phase II Pilot study of concurrent etoposide and cisplatin plus accelerated hyperfractionated thoracic radiotherapy followed by irinotecan and cisplatin for limited-stage small cell lung cancer Safety of CDDP + irinotecan therapy following combined CDDP + VP-16 and radiation therapy was demonstrated, and it was decided that this therapy would be used in the JCOG0202 study (11) 0101DI Phase II A phase II study of weekly taxol chemotherapy for platinum refractory small cell lung cancer 0202 Phase III A phase III study comparing etoposide and cisplatin (EP) with irinotecan and cisplatin (IP) following EP plus concurrent accelerated hyperfractionated thoracic irradiation (EP/TRT) for the treatment of limited-stage small-cell lung cancer No superiority of CDDP + irinotecan therapy was demonstrated (12) 0509 Phase III A phase III randomized, multicenter study comparing irinotecan and cisplatin (IP) with amrubicin and cisplatin (AP) for the treatment of extensive-stage small-cell lung cancer No superiority of CDDP + amrubicin therapy was demonstrated (13) 0605 Phase III A phase III study comparing irinotecan, cisplatin and etoposide (PEI) with nogitecan for the treatment of relapsed small-cell lung cancer Superiority of PEI therapy was demonstrated (14) 0901 Phase II Phase II study of amrubicin in patients with small-cell lung cancer that is refractory or relapsed within 90 days of completing previous treatment Effectiveness of amrubicin was demonstrated (15) 1011 Phase II Randomized phase II trial of CODE or amrubicin and cisplatin chemotherapy following concurrent cisplatin, etoposide and accelerated hyperfractionation thoracic radiotherapy for limited disease small cell lung cancer Neither group showed the 1-year aggravation-free survival rate expected for advancement to evaluation of the test treatment by a phase III trial (16) 1201 Phase II/III A phase II/III study comparing carboplatin and irinotecan (CI) with carboplatin and etoposide (CE) for the treatment of elderly extended-stage small-cell lung cancer (JCOG1201, elderly ED-SCLC/CI vs. CE) Follow-up after completion of enrollment 1205/1206 Phase III A phase III study comparing irinotecan and cisplatin with etoposide and cisplatin for adjuvant chemotherapy of completely resected pulmonary high-grade neuroendocrine carcinoma Follow-up after completion of enrollment Open in new tab Table 2 Development of treatment strategies for small cell lung cancer JCOG No. . Phase, etc. . Study outline . Results . Reference . 8502 Phase III Randomized trial of cyclophosphamide, doxorubicin and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer The median survival time was 9.9 months with CAV, 9.9 months with PE, and 11.8 months with CAV/PE (1) 8803 Phase II Concurrent cisplatin-etoposide chemotherapy plus thoracic radiotherapy for limited-stage small cell lung cancer CDDP + VP-16 therapy combined with chest radiation resulted in a median survival time of 14.8 months and a 2-year survival rate of 20% (2) 8809 Phase I/II A study of dose escalation of teniposide (VM-26) plus cisplatin (CDDP) with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in patients with advanced small cell lung cancer Teniposide 100 mg/m2/day for 5 days was determined to be the recommended dose level/duration for teniposide (3) 9104 Phase III Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer Survival was better with concurrent chemotherapy + radiotherapy than with sequential chemotherapy + radiotherapy (4) 9106 Phase III Phase III study of intensive weekly chemotherapy with recombinant human granulocyte colony-stimulating factor versus standard chemotherapy in extensive-disease small-cell lung cancer No superiority of the test therapy (CODE therapy) over CAV/PE therapy was demonstrated (5) 9111 Phase II Cisplatin plus oral etoposide in the treatment of patients with advanced small cell lung cancer Long-term oral VP-16 therapy was effective, but was associated with prolonged gastrointestinal toxicity (6) 9409 Phase II Phase II study of area under the plasma-concentration-versus-time curve-based carboplatin plus standard-dose intravenous etoposide in elderly patients with small-cell lung cancer A phase III trial of CBDCA + VP-16 for elderly patients was judged as being warranted (7) 9509 Phase II A phase II study of concurrent cisplatin/etoposide (PE) and twice-daily thoracic radiotherapy (BID TRT) followed by weekly dose intensive regimen (CODE) with human granulocyte-colony stimulating factor (G-CSF) for limited stage (LS) small cell lung cancer (SCLC) The study was discontinued prematurely because evidence for the better treatment outcomes of twice-daily irradiation was established during the study (which involved only once-daily irradiation) and because the planned duration of CODE therapy was long 9511 Phase III Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer Superiority of CDDP + irinotecan therapy over CDDP + VP-16 therapy was demonstrated (8) 9702 Phase I/II Randomized phase III trial of carboplatin plus etoposide vs. split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer Although no superiority of CBDCA + VP-16 therapy over CDDP + VP-16 therapy was demonstrated, the CBDCA + VP16 regimen was judged as being a useful additional alternative for treatment (9) 9902DI Phase II Randomized phase II study of cisplatin, irinotecan and etoposide combinations administered weekly or every 4 weeks for extensive small-cell lung cancer On the basis of the response rate, the 4-week dosing regimen was judged as being suitable as the test therapy for the phase III trial (10) 9903DI Phase II Pilot study of concurrent etoposide and cisplatin plus accelerated hyperfractionated thoracic radiotherapy followed by irinotecan and cisplatin for limited-stage small cell lung cancer Safety of CDDP + irinotecan therapy following combined CDDP + VP-16 and radiation therapy was demonstrated, and it was decided that this therapy would be used in the JCOG0202 study (11) 0101DI Phase II A phase II study of weekly taxol chemotherapy for platinum refractory small cell lung cancer 0202 Phase III A phase III study comparing etoposide and cisplatin (EP) with irinotecan and cisplatin (IP) following EP plus concurrent accelerated hyperfractionated thoracic irradiation (EP/TRT) for the treatment of limited-stage small-cell lung cancer No superiority of CDDP + irinotecan therapy was demonstrated (12) 0509 Phase III A phase III randomized, multicenter study comparing irinotecan and cisplatin (IP) with amrubicin and cisplatin (AP) for the treatment of extensive-stage small-cell lung cancer No superiority of CDDP + amrubicin therapy was demonstrated (13) 0605 Phase III A phase III study comparing irinotecan, cisplatin and etoposide (PEI) with nogitecan for the treatment of relapsed small-cell lung cancer Superiority of PEI therapy was demonstrated (14) 0901 Phase II Phase II study of amrubicin in patients with small-cell lung cancer that is refractory or relapsed within 90 days of completing previous treatment Effectiveness of amrubicin was demonstrated (15) 1011 Phase II Randomized phase II trial of CODE or amrubicin and cisplatin chemotherapy following concurrent cisplatin, etoposide and accelerated hyperfractionation thoracic radiotherapy for limited disease small cell lung cancer Neither group showed the 1-year aggravation-free survival rate expected for advancement to evaluation of the test treatment by a phase III trial (16) 1201 Phase II/III A phase II/III study comparing carboplatin and irinotecan (CI) with carboplatin and etoposide (CE) for the treatment of elderly extended-stage small-cell lung cancer (JCOG1201, elderly ED-SCLC/CI vs. CE) Follow-up after completion of enrollment 1205/1206 Phase III A phase III study comparing irinotecan and cisplatin with etoposide and cisplatin for adjuvant chemotherapy of completely resected pulmonary high-grade neuroendocrine carcinoma Follow-up after completion of enrollment JCOG No. . Phase, etc. . Study outline . Results . Reference . 8502 Phase III Randomized trial of cyclophosphamide, doxorubicin and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer The median survival time was 9.9 months with CAV, 9.9 months with PE, and 11.8 months with CAV/PE (1) 8803 Phase II Concurrent cisplatin-etoposide chemotherapy plus thoracic radiotherapy for limited-stage small cell lung cancer CDDP + VP-16 therapy combined with chest radiation resulted in a median survival time of 14.8 months and a 2-year survival rate of 20% (2) 8809 Phase I/II A study of dose escalation of teniposide (VM-26) plus cisplatin (CDDP) with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in patients with advanced small cell lung cancer Teniposide 100 mg/m2/day for 5 days was determined to be the recommended dose level/duration for teniposide (3) 9104 Phase III Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer Survival was better with concurrent chemotherapy + radiotherapy than with sequential chemotherapy + radiotherapy (4) 9106 Phase III Phase III study of intensive weekly chemotherapy with recombinant human granulocyte colony-stimulating factor versus standard chemotherapy in extensive-disease small-cell lung cancer No superiority of the test therapy (CODE therapy) over CAV/PE therapy was demonstrated (5) 9111 Phase II Cisplatin plus oral etoposide in the treatment of patients with advanced small cell lung cancer Long-term oral VP-16 therapy was effective, but was associated with prolonged gastrointestinal toxicity (6) 9409 Phase II Phase II study of area under the plasma-concentration-versus-time curve-based carboplatin plus standard-dose intravenous etoposide in elderly patients with small-cell lung cancer A phase III trial of CBDCA + VP-16 for elderly patients was judged as being warranted (7) 9509 Phase II A phase II study of concurrent cisplatin/etoposide (PE) and twice-daily thoracic radiotherapy (BID TRT) followed by weekly dose intensive regimen (CODE) with human granulocyte-colony stimulating factor (G-CSF) for limited stage (LS) small cell lung cancer (SCLC) The study was discontinued prematurely because evidence for the better treatment outcomes of twice-daily irradiation was established during the study (which involved only once-daily irradiation) and because the planned duration of CODE therapy was long 9511 Phase III Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer Superiority of CDDP + irinotecan therapy over CDDP + VP-16 therapy was demonstrated (8) 9702 Phase I/II Randomized phase III trial of carboplatin plus etoposide vs. split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer Although no superiority of CBDCA + VP-16 therapy over CDDP + VP-16 therapy was demonstrated, the CBDCA + VP16 regimen was judged as being a useful additional alternative for treatment (9) 9902DI Phase II Randomized phase II study of cisplatin, irinotecan and etoposide combinations administered weekly or every 4 weeks for extensive small-cell lung cancer On the basis of the response rate, the 4-week dosing regimen was judged as being suitable as the test therapy for the phase III trial (10) 9903DI Phase II Pilot study of concurrent etoposide and cisplatin plus accelerated hyperfractionated thoracic radiotherapy followed by irinotecan and cisplatin for limited-stage small cell lung cancer Safety of CDDP + irinotecan therapy following combined CDDP + VP-16 and radiation therapy was demonstrated, and it was decided that this therapy would be used in the JCOG0202 study (11) 0101DI Phase II A phase II study of weekly taxol chemotherapy for platinum refractory small cell lung cancer 0202 Phase III A phase III study comparing etoposide and cisplatin (EP) with irinotecan and cisplatin (IP) following EP plus concurrent accelerated hyperfractionated thoracic irradiation (EP/TRT) for the treatment of limited-stage small-cell lung cancer No superiority of CDDP + irinotecan therapy was demonstrated (12) 0509 Phase III A phase III randomized, multicenter study comparing irinotecan and cisplatin (IP) with amrubicin and cisplatin (AP) for the treatment of extensive-stage small-cell lung cancer No superiority of CDDP + amrubicin therapy was demonstrated (13) 0605 Phase III A phase III study comparing irinotecan, cisplatin and etoposide (PEI) with nogitecan for the treatment of relapsed small-cell lung cancer Superiority of PEI therapy was demonstrated (14) 0901 Phase II Phase II study of amrubicin in patients with small-cell lung cancer that is refractory or relapsed within 90 days of completing previous treatment Effectiveness of amrubicin was demonstrated (15) 1011 Phase II Randomized phase II trial of CODE or amrubicin and cisplatin chemotherapy following concurrent cisplatin, etoposide and accelerated hyperfractionation thoracic radiotherapy for limited disease small cell lung cancer Neither group showed the 1-year aggravation-free survival rate expected for advancement to evaluation of the test treatment by a phase III trial (16) 1201 Phase II/III A phase II/III study comparing carboplatin and irinotecan (CI) with carboplatin and etoposide (CE) for the treatment of elderly extended-stage small-cell lung cancer (JCOG1201, elderly ED-SCLC/CI vs. CE) Follow-up after completion of enrollment 1205/1206 Phase III A phase III study comparing irinotecan and cisplatin with etoposide and cisplatin for adjuvant chemotherapy of completely resected pulmonary high-grade neuroendocrine carcinoma Follow-up after completion of enrollment Open in new tab JCOG8803 study was the first study for limited disease SCLC and was designed as a phase II trial aimed at evaluating the efficacy and safety of chemoradiotherapy, i.e. six cycles of chemotherapy with CDDP (80 mg/m2, Day 1) and VP-16 (100 mg/m2, Days 1–3) combined with chest radiation (40–50 Gy) during the first cycle (Days 2–12) and second cycle (Days 29–47) of chemotherapy. A total of 66 patients were registered, and a response rate and median survival time of 94.9% (complete response [CR] 40.7%) and 14.8 months, respectively, were obtained (2). Later, the JCOG9104 study was carried out to determine the optimum timing of radiation. In that study, 231 patients were allocated at random to the concurrent chemoradiotherapy group (1.5 Gy chest irradiation twice daily for 15 days combined with PE therapy beginning on Day 2 of the first cycle) and the sequential chemoradiotherapy group (irradiation after the end of the fourth cycle of PE therapy). Although the difference was not statistically significant, the median survival time was longer in the concurrent chemotherapy group (27.2 months) than in the sequential chemotherapy group (19.7 months). After this study, concurrent chemotherapy began to be considered as the standard therapy for limited disease SCLC (4). The JCOG9509 study, conducted slightly later, was aimed at improving the response of this type of SCLC to CODE therapy administered after two cycles of PE therapy and chest radiation (once daily). The study was, however, discontinued prematurely because of publication of a report, meanwhile, of a better prognosis following twice-daily chest irradiation, an excessively long treatment time of CODE therapy, etc. Although no attempts have been made to develop strategies of treating limited disease SCLC, no new standard therapy has been established yet, to date. To utilize irinotecan, a drug that serves as a standard drug for the treatment of extensive disease SCLC, the JCOG9903DI study was carried out as a pilot study; the study was a trial of CDDP + irinotecan therapy following concurrent chemoradiotherapy (CDDP + VP-16 combined with multi-split chest irradiation), and confirmed the absence of any safety problem (11). ‘DI’ is an abbreviation for datacenter-independent, meaning that the data of the study are controlled by investigators (without the involvement of any data center), whilst the JCOG evaluates the protocols. Following this result, a phase III study (JCOG0202) was carried out of CDDP + VP-16 therapy or cisplatin + irinotecan therapy after the above-mentioned concurrent chemoradiotherapy regimen (CDDP + VP-16 combined with multi-split chest irradiation) for limited disease SCLC, which yielded similar results in both groups, demonstrating the lack of need for switching the chemotherapy to CDDP + irinotecan therapy as a means of consolidation therapy (12). In the JCOG1011 study, which was carried out as a randomized phase II trial aimed at examining whether or not combined amrubicin + CDDP therapy or CODE therapy, which have attracted close attention as strategies for treating extensive disease SCLC, would deserve further development as a consolidation regimen after chemoradiotherapy. The results of this study failed to satisfy the expectation in either group (16). In regard to SCLC in elderly patients, efforts at exploring an optimum treatment strategy for the elderly began to be made in the 1990s. The JCOG9409 study was a phase II trial of carboplatin (CBDCA, AUC5, Day 1) + VP-16 (100 mg/m2, Day 1–3) (CBDCA + VP-16) therapy in elderly patients with SCLC. It yielded good responses and controllable toxicological profiles, which led to it being judged as warranting further development (7). The subsequent JCOG9702 study was designed as a phase III trial of concurrent chemoradiotherapy with CBDCA + VP-16 and sequential chemoradiotherapy with CDDP + VP-16 in elderly and poor-risk patients with SCLC. In this study, no superiority of CBDCA + VP-16 over CDDP + VP-16 was demonstrated, but the outcomes and safety were comparable between the two therapies, leading to the judgment that CBDCA + VP-16 therapy also could serve as a useful treatment alternative (9). At present, registration of SCLC patients for a phase II/III trial of CBDCA + VP-16 therapy and CBDCA + irinotecan therapy is under way (JCOG1201). Also, a randomized phase III trial of CDDP + irinotecan therapy and CDDP + VP-16 therapy is under way for completely resected cases of high-malignant-grade neuroendocrine lung cancers, including SCLC, in cooperation with the JCOG Lung Cancer Surgical Study Group (JCOG1205/1206 study). Development of treatment strategies for non-small cell lung cancer (NSCLC) Numerous explorative studies have been conducted by the JCOG from the latter half of the 1980s to the 1990s (Table 3). Various attempts have been made, including a phase II trial of combined long-term oral VP-16 treatment + CDDP treatment (JCOG9008 study), a phase I/II trial of weekly CDDP + VP-16 therapy (JCOG9009 study), a phase I trial to determine the dose level of irinotecan to be used in combination with CDDP + vindesine (JCOG9110 study), a phase II trial of combined irinotecan + VP-16 therapy (JCOG9302 study), a phase I/II trial of continuous chemotherapy with irinotecan + VP-16 (JCOG9406 study), a phase I/II trial of combined CDDP + irinotecan + VP-16 therapy (JCOG9512 study), a phase I/II trial of combined gemcitabine + irinotecan therapy (JCOG9904DI study), etc., but further development was given up for many of these therapies (18, 20, 22, 23, 25, 31). Table 3 Development of treatment strategies for non-small cell lung cancer JCOG No. . Phase, etc. . Study outline . Results . Reference . 8902 Phase II Phase II study of concurrent chemotherapy and radiotherapy for unresectable stage III non-small-cell lung cancer: long-term follow-up results Long-term results of CDDP + vindesine therapy combined with radiotherapy were shown (17) 9008 Phase II A phase II study of long-term etoposide oral administration therapy plus cisplatin therapy in patients with non-small cell lung cancer Effectiveness and safety of long-term oral etoposide therapy and also of its use in combination with CDDP were demonstrated 9009 Phase I/II A combination phase I/II study of weekly cisplatin and etoposide therapy in patients with unresectable non-small cell lung cancer The therapy was judged as being unsuitable for further development because of poor efficacy 9110 Phase I Phase I clinical trial of irinotecan (CPT-11), 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy-camptothecin, and cisplatin in combination with fixed dose of vindesine in advanced non-small cell lung cancer The recommended dose levels of vindesine and CDDP for a phase II trial were determined to be 37.5 mg/m2 (Day 1) and 80 mg/m2 (Day 8), respectively (18) 9201 Phase II A phase II study of chemotherapy and concurrent thoracic radiotherapy in patients with unresectable stage III non-small cell lung cancer 9202 Phase III Phase III study of intensive weekly chemotherapy with recombinant human granulocyte colony-stimulating factor versus standard chemotherapy in extensive-disease small-cell lung cancer The superiority of concurrent over sequential chemotherapy + radiotherapy was demonstrated (19) 9302 Phase II Phase II study of irinotecan and etoposide in patients with metastatic non-small-cell lung cancer No superior outcome over the standard therapy was shown (20) 9306 Phase II Phase II study of twice-daily high-dose thoracic radiotherapy alternating with cisplatin and vindesine for unresectable stage III non-small-cell lung cancer No superior outcome over the standard therapy was shown (21) 9405 Phase I/II Dose-finding study of irinotecan and cisplatin plus concurrent radiotherapy for unresectable stage III non-small-cell lung cancer The recommended dose levels were set for CDDP + irinotecan therapy combined with chest radiation (22) 9406 Phase I/II Phase I study of sequentially administered topoisomerase I inhibitor (irinotecan) and topoisomerase II inhibitor (etoposide) for metastatic non-small-cell lung cancer Continuous treatment with irinotecan + VP-16 was judged as being unsuitable for further development because of high toxicity (23) 9504 Phase I/II A phase II study of irinotecan and concurrent radiotherapy in locally advanced non-small cell lung cancer (24) 9510 Phase II A phase II study of cisplatin and irinotecan as induction chemotherapy followed by accelerated hyperfractionated thoracic radiotherapy with daily low-dose carboplatin in unresectable stage III non-small cell lung cancer This regimen was demonstrated to be ineffective 9512 Phase I/II A phase I and II study of a combination of irinotecan etoposide, and cisplatin chemotherapy in patients with advanced non-small cell lung cancer (25) 9601 Phase I Randomized phase I study of standard-fractionated or accelerated-hyperfractionated radiotherapy with concurrent cisplatin and vindesine for unresectable non-small cell lung cancer Increasing the radiation dose for radiotherapy combined with CDDP + vindesine therapy was judged as being unrecommendable, because of the reinforced toxicity (26) 9704 Phase I/II Phase I/II study of docetaxel plus cisplatin in patients with unresectable stage III non-small cell lung cancer The MTD was reached at a dose level lower than the anticipated dose in the phase I trial, and the trial was not advanced to phase II, because no efficacy could be expected 9706 Phase II A phase II study of induction chemotherapy (IND CT) with CPT-11 and cisplatin followed by thoracic radiation (TRT) combined with weekly CPT-11 in patients with unresectable stage III non-small-cell lung cancer (NSCLC) The therapy was judged as being unsuitable for further development, because of the small percentage of patients in whom the therapy could be completed (27) 9807 Phase I/II Dose escalation study of paclitaxel in combination with fixed-dose irinotecan in patients with advanced non-small cell lung cancer Paclitaxel 160 mg/m2 and irinotecan 60 mg/m2 at intervals of 2 weeks were determined as the recommended dose levels (28) 9812 Phase III Standard thoracic radiotherapy with or without concurrent daily low-dose carboplatin in elderly patients with locally advanced non-small cell lung cancer The therapy was discontinued prematurely because of a high incidence of treatment-related death. A repetition of the study (JCOG0301) is planned after improving the radiotherapy QA/QC (29) 9901DI Phase I A phase I/II study of cisplatin plus docetaxel with concurrent thoracic radiation therapy in patients with unresectable stage III non-small cell lung cancer Docetaxel 50 mg/m2 + CDDP 80 mg/m2 were determined as the recommended dose levels (30) 9904DI Phase I/II A phase I/II study of gemcitabine plus irinotecan for advanced non-small cell lung cancer The therapy was judged as being unsuitable for further development because of both poor efficacy and poor safety (31) 9909DI Phase I/II A pilot phase I/II study of vinorelbine and gemcitabine combined therapy in patients with geriatric advanced non-small cell lung cancer The study was discontinued prematurely because of publication of the MILES test data during the study, etc. 9910DI Phase I/II Dose-escalating and pharmacokinetic study of a weekly combination of paclitaxel and carboplatin for inoperable non-small cell lung cancer The effectiveness/safety of weekly CBDCA + PTX therapy was demonstrated (32) 0003A Ancillary A study of long-term survival rate in unresectable advanced non-small cell lung cancer The 5-year survival rate following chemoradiotherapy was 12% (33) 0104 Phase III Docetaxel (D) versus docetaxel plus gemcitabine (DG) for second-line treatment of non-small cell lung cancer (NSCLC): results of a JCOG randomized trial The study was discontinued prematurely because of the lung damage seen in the combined therapy group (34) 0207 Phase III Randomized controlled trial comparing docetaxel-cisplatin combination with docetaxel alone in elderly patients with advanced non-small-cell lung cancer The study was discontinued prematurely because of the concern with the use of uncombined docetaxel therapy for patients aged between 70 and 74 years. A repetition of the study (JCOG0803) is planned in patients aged 75 years and over (35) 0301 Phase III Randomized controlled trial to evaluate standard thoracic radiotherapy with or without concurrent daily low-dose carboplatin in elderly patients with locally advanced non-small cell lung cancer Superiority of concurrent low-dose daily CBDCA with chest radiation was demonstrated (36) 0301A1 Ancillary A long-term follow-up outcome of JCOG0301: randomized controlled trial to evaluate standard thoracic radiotherapy with or without concurrent daily low-dose carboplatin in elderly patients with locally advanced non-small cell lung cancer Long term follow-up data was reported as a poster presentation at the ASCO2017 meeting 0402 Phase I/II A phase I/II study of gefitinib and concurrent thoracic radiation therapy after cisplatin and vinorelbine for locally advanced non-small cell lung cancer The therapy was judged as being unsuitable for further development because it failed to satisfy the criteria of feasibility set forth in the protocol and because the frequency of EGFR gene mutation-positive stage III non-small cell lung carcinoma is low (37) 0803 Phase III Randomized controlled trial comparing docetaxel-cisplatin combination with docetaxel alone in elderly patients with advanced non-small-cell lung cancer Superiority of CDDP + docetaxel therapy was not demonstrated (38) 1115A Ancillary An integrated analysis of comprehensive geriatric assessment (CGA) in elderly non-small cell lung cancer (NSCLC) 1210 Phase III A phase III study comparing carboplatin plus pemetrexed followed by maintenance pemetrexed with docetaxel in elderly patients with advanced non-squamous non-small-cell lung cancer (JCOG1210/WJOG7813L CBDCA/PEM vs DOC Phase III) Registration completed and follow-up under way as of January 2018 1404 Phase III A phase III study comparing gefitinib/osimertinib and inserted cisplatin and pemetrexed with gefitinib/osimertinib as a first-line treatment for patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR activating mutation (JCOG1404/WJOG8214L, AGAIN study) Registration under way as of January 2020 1404A1 Ancillary Biomarker study to clarify the mechanism of acquiring resistance to EGFR-TKI and usefulness of liquid biopsy in EGFR mutation positive non-small lung cancer Registration under way as of January 2020 1414A Ancillary A pooled analysis of lung cancer subscale in elderly patients with advanced non-small cell lung cancer—JCOG0207 and JCOG0803/WJOG4307L 1701 Phase III Randomized phase III study comparing cessation or continuation of PD-1 pathway blockade for patients with advanced non-small-cell lung cancer (SAVE study) Registration under way as of January 2020 1701A1 Ancillary Exploratory analysis of liquid biopsy for the predictive factors associated with cessation of PD-1 pathway blockade Registration under way as of January 2020 1707INT Phase II A randomized phase II study of carboplatin plus nab-paclitaxel with or without nintedanib for advanced non-small-cell lung cancer with idiopathic pulmonary fibrosis (J-SONIC) Registration under way as of January 2020 1810INT Phase III Phase III study of afatinib or chemotherapy in patients with non-small cell lung cancer harbouring sensitizing uncommon epidermal growth factor receptor mutations (ACHILLES) Registration under way as of January 2020 JCOG No. . Phase, etc. . Study outline . Results . Reference . 8902 Phase II Phase II study of concurrent chemotherapy and radiotherapy for unresectable stage III non-small-cell lung cancer: long-term follow-up results Long-term results of CDDP + vindesine therapy combined with radiotherapy were shown (17) 9008 Phase II A phase II study of long-term etoposide oral administration therapy plus cisplatin therapy in patients with non-small cell lung cancer Effectiveness and safety of long-term oral etoposide therapy and also of its use in combination with CDDP were demonstrated 9009 Phase I/II A combination phase I/II study of weekly cisplatin and etoposide therapy in patients with unresectable non-small cell lung cancer The therapy was judged as being unsuitable for further development because of poor efficacy 9110 Phase I Phase I clinical trial of irinotecan (CPT-11), 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy-camptothecin, and cisplatin in combination with fixed dose of vindesine in advanced non-small cell lung cancer The recommended dose levels of vindesine and CDDP for a phase II trial were determined to be 37.5 mg/m2 (Day 1) and 80 mg/m2 (Day 8), respectively (18) 9201 Phase II A phase II study of chemotherapy and concurrent thoracic radiotherapy in patients with unresectable stage III non-small cell lung cancer 9202 Phase III Phase III study of intensive weekly chemotherapy with recombinant human granulocyte colony-stimulating factor versus standard chemotherapy in extensive-disease small-cell lung cancer The superiority of concurrent over sequential chemotherapy + radiotherapy was demonstrated (19) 9302 Phase II Phase II study of irinotecan and etoposide in patients with metastatic non-small-cell lung cancer No superior outcome over the standard therapy was shown (20) 9306 Phase II Phase II study of twice-daily high-dose thoracic radiotherapy alternating with cisplatin and vindesine for unresectable stage III non-small-cell lung cancer No superior outcome over the standard therapy was shown (21) 9405 Phase I/II Dose-finding study of irinotecan and cisplatin plus concurrent radiotherapy for unresectable stage III non-small-cell lung cancer The recommended dose levels were set for CDDP + irinotecan therapy combined with chest radiation (22) 9406 Phase I/II Phase I study of sequentially administered topoisomerase I inhibitor (irinotecan) and topoisomerase II inhibitor (etoposide) for metastatic non-small-cell lung cancer Continuous treatment with irinotecan + VP-16 was judged as being unsuitable for further development because of high toxicity (23) 9504 Phase I/II A phase II study of irinotecan and concurrent radiotherapy in locally advanced non-small cell lung cancer (24) 9510 Phase II A phase II study of cisplatin and irinotecan as induction chemotherapy followed by accelerated hyperfractionated thoracic radiotherapy with daily low-dose carboplatin in unresectable stage III non-small cell lung cancer This regimen was demonstrated to be ineffective 9512 Phase I/II A phase I and II study of a combination of irinotecan etoposide, and cisplatin chemotherapy in patients with advanced non-small cell lung cancer (25) 9601 Phase I Randomized phase I study of standard-fractionated or accelerated-hyperfractionated radiotherapy with concurrent cisplatin and vindesine for unresectable non-small cell lung cancer Increasing the radiation dose for radiotherapy combined with CDDP + vindesine therapy was judged as being unrecommendable, because of the reinforced toxicity (26) 9704 Phase I/II Phase I/II study of docetaxel plus cisplatin in patients with unresectable stage III non-small cell lung cancer The MTD was reached at a dose level lower than the anticipated dose in the phase I trial, and the trial was not advanced to phase II, because no efficacy could be expected 9706 Phase II A phase II study of induction chemotherapy (IND CT) with CPT-11 and cisplatin followed by thoracic radiation (TRT) combined with weekly CPT-11 in patients with unresectable stage III non-small-cell lung cancer (NSCLC) The therapy was judged as being unsuitable for further development, because of the small percentage of patients in whom the therapy could be completed (27) 9807 Phase I/II Dose escalation study of paclitaxel in combination with fixed-dose irinotecan in patients with advanced non-small cell lung cancer Paclitaxel 160 mg/m2 and irinotecan 60 mg/m2 at intervals of 2 weeks were determined as the recommended dose levels (28) 9812 Phase III Standard thoracic radiotherapy with or without concurrent daily low-dose carboplatin in elderly patients with locally advanced non-small cell lung cancer The therapy was discontinued prematurely because of a high incidence of treatment-related death. A repetition of the study (JCOG0301) is planned after improving the radiotherapy QA/QC (29) 9901DI Phase I A phase I/II study of cisplatin plus docetaxel with concurrent thoracic radiation therapy in patients with unresectable stage III non-small cell lung cancer Docetaxel 50 mg/m2 + CDDP 80 mg/m2 were determined as the recommended dose levels (30) 9904DI Phase I/II A phase I/II study of gemcitabine plus irinotecan for advanced non-small cell lung cancer The therapy was judged as being unsuitable for further development because of both poor efficacy and poor safety (31) 9909DI Phase I/II A pilot phase I/II study of vinorelbine and gemcitabine combined therapy in patients with geriatric advanced non-small cell lung cancer The study was discontinued prematurely because of publication of the MILES test data during the study, etc. 9910DI Phase I/II Dose-escalating and pharmacokinetic study of a weekly combination of paclitaxel and carboplatin for inoperable non-small cell lung cancer The effectiveness/safety of weekly CBDCA + PTX therapy was demonstrated (32) 0003A Ancillary A study of long-term survival rate in unresectable advanced non-small cell lung cancer The 5-year survival rate following chemoradiotherapy was 12% (33) 0104 Phase III Docetaxel (D) versus docetaxel plus gemcitabine (DG) for second-line treatment of non-small cell lung cancer (NSCLC): results of a JCOG randomized trial The study was discontinued prematurely because of the lung damage seen in the combined therapy group (34) 0207 Phase III Randomized controlled trial comparing docetaxel-cisplatin combination with docetaxel alone in elderly patients with advanced non-small-cell lung cancer The study was discontinued prematurely because of the concern with the use of uncombined docetaxel therapy for patients aged between 70 and 74 years. A repetition of the study (JCOG0803) is planned in patients aged 75 years and over (35) 0301 Phase III Randomized controlled trial to evaluate standard thoracic radiotherapy with or without concurrent daily low-dose carboplatin in elderly patients with locally advanced non-small cell lung cancer Superiority of concurrent low-dose daily CBDCA with chest radiation was demonstrated (36) 0301A1 Ancillary A long-term follow-up outcome of JCOG0301: randomized controlled trial to evaluate standard thoracic radiotherapy with or without concurrent daily low-dose carboplatin in elderly patients with locally advanced non-small cell lung cancer Long term follow-up data was reported as a poster presentation at the ASCO2017 meeting 0402 Phase I/II A phase I/II study of gefitinib and concurrent thoracic radiation therapy after cisplatin and vinorelbine for locally advanced non-small cell lung cancer The therapy was judged as being unsuitable for further development because it failed to satisfy the criteria of feasibility set forth in the protocol and because the frequency of EGFR gene mutation-positive stage III non-small cell lung carcinoma is low (37) 0803 Phase III Randomized controlled trial comparing docetaxel-cisplatin combination with docetaxel alone in elderly patients with advanced non-small-cell lung cancer Superiority of CDDP + docetaxel therapy was not demonstrated (38) 1115A Ancillary An integrated analysis of comprehensive geriatric assessment (CGA) in elderly non-small cell lung cancer (NSCLC) 1210 Phase III A phase III study comparing carboplatin plus pemetrexed followed by maintenance pemetrexed with docetaxel in elderly patients with advanced non-squamous non-small-cell lung cancer (JCOG1210/WJOG7813L CBDCA/PEM vs DOC Phase III) Registration completed and follow-up under way as of January 2018 1404 Phase III A phase III study comparing gefitinib/osimertinib and inserted cisplatin and pemetrexed with gefitinib/osimertinib as a first-line treatment for patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR activating mutation (JCOG1404/WJOG8214L, AGAIN study) Registration under way as of January 2020 1404A1 Ancillary Biomarker study to clarify the mechanism of acquiring resistance to EGFR-TKI and usefulness of liquid biopsy in EGFR mutation positive non-small lung cancer Registration under way as of January 2020 1414A Ancillary A pooled analysis of lung cancer subscale in elderly patients with advanced non-small cell lung cancer—JCOG0207 and JCOG0803/WJOG4307L 1701 Phase III Randomized phase III study comparing cessation or continuation of PD-1 pathway blockade for patients with advanced non-small-cell lung cancer (SAVE study) Registration under way as of January 2020 1701A1 Ancillary Exploratory analysis of liquid biopsy for the predictive factors associated with cessation of PD-1 pathway blockade Registration under way as of January 2020 1707INT Phase II A randomized phase II study of carboplatin plus nab-paclitaxel with or without nintedanib for advanced non-small-cell lung cancer with idiopathic pulmonary fibrosis (J-SONIC) Registration under way as of January 2020 1810INT Phase III Phase III study of afatinib or chemotherapy in patients with non-small cell lung cancer harbouring sensitizing uncommon epidermal growth factor receptor mutations (ACHILLES) Registration under way as of January 2020 Open in new tab Table 3 Development of treatment strategies for non-small cell lung cancer JCOG No. . Phase, etc. . Study outline . Results . Reference . 8902 Phase II Phase II study of concurrent chemotherapy and radiotherapy for unresectable stage III non-small-cell lung cancer: long-term follow-up results Long-term results of CDDP + vindesine therapy combined with radiotherapy were shown (17) 9008 Phase II A phase II study of long-term etoposide oral administration therapy plus cisplatin therapy in patients with non-small cell lung cancer Effectiveness and safety of long-term oral etoposide therapy and also of its use in combination with CDDP were demonstrated 9009 Phase I/II A combination phase I/II study of weekly cisplatin and etoposide therapy in patients with unresectable non-small cell lung cancer The therapy was judged as being unsuitable for further development because of poor efficacy 9110 Phase I Phase I clinical trial of irinotecan (CPT-11), 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy-camptothecin, and cisplatin in combination with fixed dose of vindesine in advanced non-small cell lung cancer The recommended dose levels of vindesine and CDDP for a phase II trial were determined to be 37.5 mg/m2 (Day 1) and 80 mg/m2 (Day 8), respectively (18) 9201 Phase II A phase II study of chemotherapy and concurrent thoracic radiotherapy in patients with unresectable stage III non-small cell lung cancer 9202 Phase III Phase III study of intensive weekly chemotherapy with recombinant human granulocyte colony-stimulating factor versus standard chemotherapy in extensive-disease small-cell lung cancer The superiority of concurrent over sequential chemotherapy + radiotherapy was demonstrated (19) 9302 Phase II Phase II study of irinotecan and etoposide in patients with metastatic non-small-cell lung cancer No superior outcome over the standard therapy was shown (20) 9306 Phase II Phase II study of twice-daily high-dose thoracic radiotherapy alternating with cisplatin and vindesine for unresectable stage III non-small-cell lung cancer No superior outcome over the standard therapy was shown (21) 9405 Phase I/II Dose-finding study of irinotecan and cisplatin plus concurrent radiotherapy for unresectable stage III non-small-cell lung cancer The recommended dose levels were set for CDDP + irinotecan therapy combined with chest radiation (22) 9406 Phase I/II Phase I study of sequentially administered topoisomerase I inhibitor (irinotecan) and topoisomerase II inhibitor (etoposide) for metastatic non-small-cell lung cancer Continuous treatment with irinotecan + VP-16 was judged as being unsuitable for further development because of high toxicity (23) 9504 Phase I/II A phase II study of irinotecan and concurrent radiotherapy in locally advanced non-small cell lung cancer (24) 9510 Phase II A phase II study of cisplatin and irinotecan as induction chemotherapy followed by accelerated hyperfractionated thoracic radiotherapy with daily low-dose carboplatin in unresectable stage III non-small cell lung cancer This regimen was demonstrated to be ineffective 9512 Phase I/II A phase I and II study of a combination of irinotecan etoposide, and cisplatin chemotherapy in patients with advanced non-small cell lung cancer (25) 9601 Phase I Randomized phase I study of standard-fractionated or accelerated-hyperfractionated radiotherapy with concurrent cisplatin and vindesine for unresectable non-small cell lung cancer Increasing the radiation dose for radiotherapy combined with CDDP + vindesine therapy was judged as being unrecommendable, because of the reinforced toxicity (26) 9704 Phase I/II Phase I/II study of docetaxel plus cisplatin in patients with unresectable stage III non-small cell lung cancer The MTD was reached at a dose level lower than the anticipated dose in the phase I trial, and the trial was not advanced to phase II, because no efficacy could be expected 9706 Phase II A phase II study of induction chemotherapy (IND CT) with CPT-11 and cisplatin followed by thoracic radiation (TRT) combined with weekly CPT-11 in patients with unresectable stage III non-small-cell lung cancer (NSCLC) The therapy was judged as being unsuitable for further development, because of the small percentage of patients in whom the therapy could be completed (27) 9807 Phase I/II Dose escalation study of paclitaxel in combination with fixed-dose irinotecan in patients with advanced non-small cell lung cancer Paclitaxel 160 mg/m2 and irinotecan 60 mg/m2 at intervals of 2 weeks were determined as the recommended dose levels (28) 9812 Phase III Standard thoracic radiotherapy with or without concurrent daily low-dose carboplatin in elderly patients with locally advanced non-small cell lung cancer The therapy was discontinued prematurely because of a high incidence of treatment-related death. A repetition of the study (JCOG0301) is planned after improving the radiotherapy QA/QC (29) 9901DI Phase I A phase I/II study of cisplatin plus docetaxel with concurrent thoracic radiation therapy in patients with unresectable stage III non-small cell lung cancer Docetaxel 50 mg/m2 + CDDP 80 mg/m2 were determined as the recommended dose levels (30) 9904DI Phase I/II A phase I/II study of gemcitabine plus irinotecan for advanced non-small cell lung cancer The therapy was judged as being unsuitable for further development because of both poor efficacy and poor safety (31) 9909DI Phase I/II A pilot phase I/II study of vinorelbine and gemcitabine combined therapy in patients with geriatric advanced non-small cell lung cancer The study was discontinued prematurely because of publication of the MILES test data during the study, etc. 9910DI Phase I/II Dose-escalating and pharmacokinetic study of a weekly combination of paclitaxel and carboplatin for inoperable non-small cell lung cancer The effectiveness/safety of weekly CBDCA + PTX therapy was demonstrated (32) 0003A Ancillary A study of long-term survival rate in unresectable advanced non-small cell lung cancer The 5-year survival rate following chemoradiotherapy was 12% (33) 0104 Phase III Docetaxel (D) versus docetaxel plus gemcitabine (DG) for second-line treatment of non-small cell lung cancer (NSCLC): results of a JCOG randomized trial The study was discontinued prematurely because of the lung damage seen in the combined therapy group (34) 0207 Phase III Randomized controlled trial comparing docetaxel-cisplatin combination with docetaxel alone in elderly patients with advanced non-small-cell lung cancer The study was discontinued prematurely because of the concern with the use of uncombined docetaxel therapy for patients aged between 70 and 74 years. A repetition of the study (JCOG0803) is planned in patients aged 75 years and over (35) 0301 Phase III Randomized controlled trial to evaluate standard thoracic radiotherapy with or without concurrent daily low-dose carboplatin in elderly patients with locally advanced non-small cell lung cancer Superiority of concurrent low-dose daily CBDCA with chest radiation was demonstrated (36) 0301A1 Ancillary A long-term follow-up outcome of JCOG0301: randomized controlled trial to evaluate standard thoracic radiotherapy with or without concurrent daily low-dose carboplatin in elderly patients with locally advanced non-small cell lung cancer Long term follow-up data was reported as a poster presentation at the ASCO2017 meeting 0402 Phase I/II A phase I/II study of gefitinib and concurrent thoracic radiation therapy after cisplatin and vinorelbine for locally advanced non-small cell lung cancer The therapy was judged as being unsuitable for further development because it failed to satisfy the criteria of feasibility set forth in the protocol and because the frequency of EGFR gene mutation-positive stage III non-small cell lung carcinoma is low (37) 0803 Phase III Randomized controlled trial comparing docetaxel-cisplatin combination with docetaxel alone in elderly patients with advanced non-small-cell lung cancer Superiority of CDDP + docetaxel therapy was not demonstrated (38) 1115A Ancillary An integrated analysis of comprehensive geriatric assessment (CGA) in elderly non-small cell lung cancer (NSCLC) 1210 Phase III A phase III study comparing carboplatin plus pemetrexed followed by maintenance pemetrexed with docetaxel in elderly patients with advanced non-squamous non-small-cell lung cancer (JCOG1210/WJOG7813L CBDCA/PEM vs DOC Phase III) Registration completed and follow-up under way as of January 2018 1404 Phase III A phase III study comparing gefitinib/osimertinib and inserted cisplatin and pemetrexed with gefitinib/osimertinib as a first-line treatment for patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR activating mutation (JCOG1404/WJOG8214L, AGAIN study) Registration under way as of January 2020 1404A1 Ancillary Biomarker study to clarify the mechanism of acquiring resistance to EGFR-TKI and usefulness of liquid biopsy in EGFR mutation positive non-small lung cancer Registration under way as of January 2020 1414A Ancillary A pooled analysis of lung cancer subscale in elderly patients with advanced non-small cell lung cancer—JCOG0207 and JCOG0803/WJOG4307L 1701 Phase III Randomized phase III study comparing cessation or continuation of PD-1 pathway blockade for patients with advanced non-small-cell lung cancer (SAVE study) Registration under way as of January 2020 1701A1 Ancillary Exploratory analysis of liquid biopsy for the predictive factors associated with cessation of PD-1 pathway blockade Registration under way as of January 2020 1707INT Phase II A randomized phase II study of carboplatin plus nab-paclitaxel with or without nintedanib for advanced non-small-cell lung cancer with idiopathic pulmonary fibrosis (J-SONIC) Registration under way as of January 2020 1810INT Phase III Phase III study of afatinib or chemotherapy in patients with non-small cell lung cancer harbouring sensitizing uncommon epidermal growth factor receptor mutations (ACHILLES) Registration under way as of January 2020 JCOG No. . Phase, etc. . Study outline . Results . Reference . 8902 Phase II Phase II study of concurrent chemotherapy and radiotherapy for unresectable stage III non-small-cell lung cancer: long-term follow-up results Long-term results of CDDP + vindesine therapy combined with radiotherapy were shown (17) 9008 Phase II A phase II study of long-term etoposide oral administration therapy plus cisplatin therapy in patients with non-small cell lung cancer Effectiveness and safety of long-term oral etoposide therapy and also of its use in combination with CDDP were demonstrated 9009 Phase I/II A combination phase I/II study of weekly cisplatin and etoposide therapy in patients with unresectable non-small cell lung cancer The therapy was judged as being unsuitable for further development because of poor efficacy 9110 Phase I Phase I clinical trial of irinotecan (CPT-11), 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy-camptothecin, and cisplatin in combination with fixed dose of vindesine in advanced non-small cell lung cancer The recommended dose levels of vindesine and CDDP for a phase II trial were determined to be 37.5 mg/m2 (Day 1) and 80 mg/m2 (Day 8), respectively (18) 9201 Phase II A phase II study of chemotherapy and concurrent thoracic radiotherapy in patients with unresectable stage III non-small cell lung cancer 9202 Phase III Phase III study of intensive weekly chemotherapy with recombinant human granulocyte colony-stimulating factor versus standard chemotherapy in extensive-disease small-cell lung cancer The superiority of concurrent over sequential chemotherapy + radiotherapy was demonstrated (19) 9302 Phase II Phase II study of irinotecan and etoposide in patients with metastatic non-small-cell lung cancer No superior outcome over the standard therapy was shown (20) 9306 Phase II Phase II study of twice-daily high-dose thoracic radiotherapy alternating with cisplatin and vindesine for unresectable stage III non-small-cell lung cancer No superior outcome over the standard therapy was shown (21) 9405 Phase I/II Dose-finding study of irinotecan and cisplatin plus concurrent radiotherapy for unresectable stage III non-small-cell lung cancer The recommended dose levels were set for CDDP + irinotecan therapy combined with chest radiation (22) 9406 Phase I/II Phase I study of sequentially administered topoisomerase I inhibitor (irinotecan) and topoisomerase II inhibitor (etoposide) for metastatic non-small-cell lung cancer Continuous treatment with irinotecan + VP-16 was judged as being unsuitable for further development because of high toxicity (23) 9504 Phase I/II A phase II study of irinotecan and concurrent radiotherapy in locally advanced non-small cell lung cancer (24) 9510 Phase II A phase II study of cisplatin and irinotecan as induction chemotherapy followed by accelerated hyperfractionated thoracic radiotherapy with daily low-dose carboplatin in unresectable stage III non-small cell lung cancer This regimen was demonstrated to be ineffective 9512 Phase I/II A phase I and II study of a combination of irinotecan etoposide, and cisplatin chemotherapy in patients with advanced non-small cell lung cancer (25) 9601 Phase I Randomized phase I study of standard-fractionated or accelerated-hyperfractionated radiotherapy with concurrent cisplatin and vindesine for unresectable non-small cell lung cancer Increasing the radiation dose for radiotherapy combined with CDDP + vindesine therapy was judged as being unrecommendable, because of the reinforced toxicity (26) 9704 Phase I/II Phase I/II study of docetaxel plus cisplatin in patients with unresectable stage III non-small cell lung cancer The MTD was reached at a dose level lower than the anticipated dose in the phase I trial, and the trial was not advanced to phase II, because no efficacy could be expected 9706 Phase II A phase II study of induction chemotherapy (IND CT) with CPT-11 and cisplatin followed by thoracic radiation (TRT) combined with weekly CPT-11 in patients with unresectable stage III non-small-cell lung cancer (NSCLC) The therapy was judged as being unsuitable for further development, because of the small percentage of patients in whom the therapy could be completed (27) 9807 Phase I/II Dose escalation study of paclitaxel in combination with fixed-dose irinotecan in patients with advanced non-small cell lung cancer Paclitaxel 160 mg/m2 and irinotecan 60 mg/m2 at intervals of 2 weeks were determined as the recommended dose levels (28) 9812 Phase III Standard thoracic radiotherapy with or without concurrent daily low-dose carboplatin in elderly patients with locally advanced non-small cell lung cancer The therapy was discontinued prematurely because of a high incidence of treatment-related death. A repetition of the study (JCOG0301) is planned after improving the radiotherapy QA/QC (29) 9901DI Phase I A phase I/II study of cisplatin plus docetaxel with concurrent thoracic radiation therapy in patients with unresectable stage III non-small cell lung cancer Docetaxel 50 mg/m2 + CDDP 80 mg/m2 were determined as the recommended dose levels (30) 9904DI Phase I/II A phase I/II study of gemcitabine plus irinotecan for advanced non-small cell lung cancer The therapy was judged as being unsuitable for further development because of both poor efficacy and poor safety (31) 9909DI Phase I/II A pilot phase I/II study of vinorelbine and gemcitabine combined therapy in patients with geriatric advanced non-small cell lung cancer The study was discontinued prematurely because of publication of the MILES test data during the study, etc. 9910DI Phase I/II Dose-escalating and pharmacokinetic study of a weekly combination of paclitaxel and carboplatin for inoperable non-small cell lung cancer The effectiveness/safety of weekly CBDCA + PTX therapy was demonstrated (32) 0003A Ancillary A study of long-term survival rate in unresectable advanced non-small cell lung cancer The 5-year survival rate following chemoradiotherapy was 12% (33) 0104 Phase III Docetaxel (D) versus docetaxel plus gemcitabine (DG) for second-line treatment of non-small cell lung cancer (NSCLC): results of a JCOG randomized trial The study was discontinued prematurely because of the lung damage seen in the combined therapy group (34) 0207 Phase III Randomized controlled trial comparing docetaxel-cisplatin combination with docetaxel alone in elderly patients with advanced non-small-cell lung cancer The study was discontinued prematurely because of the concern with the use of uncombined docetaxel therapy for patients aged between 70 and 74 years. A repetition of the study (JCOG0803) is planned in patients aged 75 years and over (35) 0301 Phase III Randomized controlled trial to evaluate standard thoracic radiotherapy with or without concurrent daily low-dose carboplatin in elderly patients with locally advanced non-small cell lung cancer Superiority of concurrent low-dose daily CBDCA with chest radiation was demonstrated (36) 0301A1 Ancillary A long-term follow-up outcome of JCOG0301: randomized controlled trial to evaluate standard thoracic radiotherapy with or without concurrent daily low-dose carboplatin in elderly patients with locally advanced non-small cell lung cancer Long term follow-up data was reported as a poster presentation at the ASCO2017 meeting 0402 Phase I/II A phase I/II study of gefitinib and concurrent thoracic radiation therapy after cisplatin and vinorelbine for locally advanced non-small cell lung cancer The therapy was judged as being unsuitable for further development because it failed to satisfy the criteria of feasibility set forth in the protocol and because the frequency of EGFR gene mutation-positive stage III non-small cell lung carcinoma is low (37) 0803 Phase III Randomized controlled trial comparing docetaxel-cisplatin combination with docetaxel alone in elderly patients with advanced non-small-cell lung cancer Superiority of CDDP + docetaxel therapy was not demonstrated (38) 1115A Ancillary An integrated analysis of comprehensive geriatric assessment (CGA) in elderly non-small cell lung cancer (NSCLC) 1210 Phase III A phase III study comparing carboplatin plus pemetrexed followed by maintenance pemetrexed with docetaxel in elderly patients with advanced non-squamous non-small-cell lung cancer (JCOG1210/WJOG7813L CBDCA/PEM vs DOC Phase III) Registration completed and follow-up under way as of January 2018 1404 Phase III A phase III study comparing gefitinib/osimertinib and inserted cisplatin and pemetrexed with gefitinib/osimertinib as a first-line treatment for patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR activating mutation (JCOG1404/WJOG8214L, AGAIN study) Registration under way as of January 2020 1404A1 Ancillary Biomarker study to clarify the mechanism of acquiring resistance to EGFR-TKI and usefulness of liquid biopsy in EGFR mutation positive non-small lung cancer Registration under way as of January 2020 1414A Ancillary A pooled analysis of lung cancer subscale in elderly patients with advanced non-small cell lung cancer—JCOG0207 and JCOG0803/WJOG4307L 1701 Phase III Randomized phase III study comparing cessation or continuation of PD-1 pathway blockade for patients with advanced non-small-cell lung cancer (SAVE study) Registration under way as of January 2020 1701A1 Ancillary Exploratory analysis of liquid biopsy for the predictive factors associated with cessation of PD-1 pathway blockade Registration under way as of January 2020 1707INT Phase II A randomized phase II study of carboplatin plus nab-paclitaxel with or without nintedanib for advanced non-small-cell lung cancer with idiopathic pulmonary fibrosis (J-SONIC) Registration under way as of January 2020 1810INT Phase III Phase III study of afatinib or chemotherapy in patients with non-small cell lung cancer harbouring sensitizing uncommon epidermal growth factor receptor mutations (ACHILLES) Registration under way as of January 2020 Open in new tab Meanwhile, attempts at developing treatment strategies have also been made for elderly patients with non-SCLC, similar to the attempts made for elderly patients with SCLC. The JCOG9901DI study is the first JCOG study specifically targeting elderly patients with advanced NSCLC and was designed as a phase I/II trial of combined vinorelbine + gemcitabine therapy (30). Unfortunately, the study was discontinued prematurely, because of publication, during this study, of the results of the MILES study suggesting a poor efficacy of the combined therapy (48). Subsequently, uncombined drug therapy was compared with platinum-combined therapy for elderly patients with NSCLC. A phase III trial (JCOG0207 study) designed to compare weekly uncombined docetaxel treatment with weekly combined CDDP + docetaxel treatment suggested difficulty in adopting weekly docetaxel treatment as the standard regimen for patients aged between 70 and 74 years, and the study was discontinued prematurely, with a decision made to repeat the study again in patients aged 75 years and over (35). The JCOG0803 study is also a study that indicated the effectiveness of the standard therapy of docetaxel administered once in 3 weeks in elderly patients aged 75 years or over with advanced NSCLC. In that study, the median survival time was 14.8 months in the docetaxel arm and 13.3 months in the weekly CDDP + docetaxel arm. Thus, the study was a negative trial. To clarify the value of platinum combination chemotherapy, JCOG1210 (docetaxel vs. CBDCA + pemetrexed) was planned. As a result, non-inferiority of CBDCA + pemetrexed was confirmed in all enrolled patients (hazard ratio for OS, 0.850; 95% confidence interval, 0.684–1.056, P < 0.01). The median survival time for docetaxel and CBDCA + pemetrexed was 15.5 and 18.7 months, respectively [JAMA oncology, in press]. The JCOG8902 study of chemoradiotherapy for locally advanced lung cancer was the first study for NSCLC to which a JCOG number was assigned. In this study, the safety and efficacy of chest radiation combined with CDDP + vindesine therapy was evaluated (17). The JCOG9202 study is a phase III trial of concurrent versus sequential chemoradiotherapy for unresectable locally advanced NSCLC. In this study, MVP therapy (administration at intervals of 28 days; CDDP 80 mg/m2, Day 1 + vindesine 3 mg/m2, Days 1 and 8) + mitomycin 8 mg/m2, Day 1) served as the chemotherapy, and chest irradiation (56 Gy) was applied from Day 2 onward (concurrent chemoradiotherapy group) or upon completion of the second cycle of chemotherapy (sequential chemoradiotherapy group). The median survival time was significantly longer in the concurrent chemoradiotherapy group (16.5 months) than that in the sequential chemoradiotherapy group (13.3 months), and the concurrent chemoradiotherapy regimen came to be adopted as the standard therapy (19). Subsequently, various explorative attempts of chemotherapy and radiotherapy for this type of lung carcinoma have been made since the 1990s, similar to those made for advanced NSCLC. The attempts include a phase II trial (JCOG9306 study) of radiotherapy and chemotherapy (CDDP + vindesine) applied in an alternating fashion, a phase I/II trial (JCOG9504 study) to determine the dose levels for CDDP + irinotecan therapy combined with chest radiation, a phase II trial (JCOG9510 study) of chest irradiation by the accelerated hyperfractionation method combined with daily CBDCA treatment after the introductory chemotherapy (CDDP + irinotecan), a phase I trial (JCOG9601 study) of combined high dose radiotherapy and chemotherapy (CDDP + irinotecan), a phase I/II trial (JCOG9704 study) to determine the dose levels for chemotherapy (CDDP + docetaxel) combined with radiotherapy, a phase II trial (JCOG9706 study) of combined irinotecan + chest radiotherapy after the introductory chemotherapy (CDDP + irinotecan), etc. (21, 22, 24, 26, 27). The JCOG has also been playing a significant role in the development of treatment strategies for elderly patients with locally advanced NSCLC, particularly chemoradiotherapy. The JCOG9812 study is a randomized phase III trial of uncombined chest radiotherapy and concurrent low-dose daily CBDCA treatment + chest irradiation. Unfortunately, the study was discontinued prematurely, because the frequency of treatment-related deaths exceeded the acceptable range even in the early phase after the start of the study. Analysis of the results of that study revealed open issues related to the quality control of radiotherapy in addition to various other factors (29). For this reason, the JCOG0301 study was carried out using a similar study design after improving the QA/QC system for radiotherapy. In that study, the median survival time following concurrent low-dose daily CBDCA treatment + chest radiotherapy was 22.4 months, statistically superior to that observed in the patients receiving uncombined chest radiotherapy (16.9 months) (36). Several JCOG studies have also been carried out to evaluate the usefulness of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (including gefitinib, whose effectiveness in EGFR gene mutation-positive patients has been established). In a phase I/II trial (JOCG0402 study) of concurrent chemotherapy with gefitinib + chest radiotherapy after chemotherapy (CDDP + vinorelbine) for patients with locally advanced NSCLC epidemiologically characterized as having a high likelihood of EGFR gene mutations, a definite safety of the therapy in terms of the concern about the potential for lung damage was confirmed, but the results failed to satisfy the criteria of feasibility based on adverse events (including liver damage), even though the patient selection in this study was not based on the presence/absence of EGFR gene mutation (37). This result combined with the small number of patients with locally advanced NSCLC and no plan for further development of this therapy was devised. At present, registration of patients for a randomized study (JCOG1404 study) to compare uncombined gefitinib/osimertinib therapy with insertion of CDDP + pemetrexed therapy during gefitinib/osimertinib therapy for EGFR gene mutation positive patients with advanced non-squamous cell NSCLC is under way. The first trial using immune checkpoint inhibitors conducted by the JCOG Lung Cancer Study Group has just started. The JCOG1701 (SAVE trial) is comparing cessation or continuation of PD-1 pathway blockade for patients with advanced NSCLC. Patients with successful treatment by PD-1 pathway blockade for 1 year are eligible and randomized to continuation or discontinuation of immune checkpoint inhibitors. Development of other treatment strategies The JCOG Lung Cancer Study Group has also been engaged in developing treatment strategies for chest malignancies other than lung cancer, supportive therapy for chemotherapy, etc. (Table 4). In particular, concerning thymoma, a phase II trial of CODE therapy for advanced/recurrent thymoma, a phase II trial of multidisciplinary treatment (combined with CODE therapy) for locally advanced thymoma, etc., have been carried out, yielding results of prospective studies in the field of rare cancers for which no standard therapies are currently available (44, 47). Also concerning supportive therapy, a phase III trial (JCOG9011 study) of high-dose methoclopramide + dexamethasone and granisetron + dexamethasone in patients receiving CDDP treatment and a phase II trial (JCOG9413 study) of high-dose dexamethasone for delayed nausea/vomiting associated with CDDP treatment have been carried out, with the former demonstraiting more favorable symptom control with granisetron+dexamethasone (39, 41). The JCOG has also conducted clinical studies of topical Picibanil therapy for cancerous pleuritis and topical bleomycin therapy for cancerous pericarditis, both of which are widely used in clinical practice. These studies include a randomzied phase II trial (JCOG9515 study) of topical bleomycin adhesion therapy, topical OK-432 adhesion therapy and combined topical CDDP + VP-16 therapy for cancerous pleuritis associated with NSCLC and a randomized comparative study (JCOG9811 study) of the efficacy of pericardial drug infusion/adhesion after pericardial drainage for the treatment of cancerous pericarditis associated with lung cancer, with the former demonstrating a greater effectivenss of Picibanil, and the latter failing to demonstrate any usefulness of adding bleomycin to pericardial drainage (43, 47). Table 4 Development of treatment strategies and supportive therapy for all lung cancers and rare chest malignancies JCOG No. . Phase, etc. . Study outline . Results . Reference . 9011 Phase III A randomized cross-over study of high-dose metoclopramide plus dexamethasone versus granisetron plus dexamethasone in patients receiving chemotherapy with high-dose cisplatin A higher antiemetic efficacy of granisetron + dexamethasone was demonstrated (39) 9408 Phase I/II Phase I study of a weekly infusion of irinotecan hydrochloride (CPT-11) and a 14-day continuous infusion of etoposide in patients with lung cancer The therapy was judged as being unsuitable for further development because of toxicity (40) 9413 Phase II Phase II study of high-dose dexamethasone-based association in acute and delayed high-dose cisplatin-induced emesis Effectiveness of high-dose dexamethasone was demonstrated (41) 9507 Phase I/II Phase I/II trial of weekly cisplatin, etoposide, and irinotecan chemotherapy for metastatic lung cancer Effectiveness of the combined therapy was demonstrated (42) 9515 Phase II Randomized phase II trial of three intrapleural therapy regimens for the management of malignant pleural effusion in previously untreated non-small cell lung cancer Pleural adhesion therapy with OK-432 was shown to be effective for improving the 4-week pleural progression-free survival rate (43) 9605 Phase II A phase-II trial of dose-dense chemotherapy in patients with disseminated thymoma The outcome of CODE therapy was similar to that of the existing regimens (44) 9606 Phase II A phase II study of combined modality with CODE (cisplatin + vincristine + doxorubicin + etoposide) chemotherapy in patients with locally advanced thymoma The outcome of CODE therapy was similar to that of the existing regimens (45) 9608 Phase I/II Phase I/II study of escalating doses of nedaplatin in combination with irinotecan for advanced non-small-cell lung cancer The effectiveness/safety of nedaplatin + irinotecan therapy was demonstrated (46) 9811 Phase III A randomized controlled trial to evaluate the efficacy of intra-pericardial instillation of a sclerosing agent after pericardial drainage in patients with malignant pericardial effusion associated with lung cancer Superiority of bleomycin in terms of the primary endpoint (effusion failure-free survival) was not demonstrated (47) JCOG No. . Phase, etc. . Study outline . Results . Reference . 9011 Phase III A randomized cross-over study of high-dose metoclopramide plus dexamethasone versus granisetron plus dexamethasone in patients receiving chemotherapy with high-dose cisplatin A higher antiemetic efficacy of granisetron + dexamethasone was demonstrated (39) 9408 Phase I/II Phase I study of a weekly infusion of irinotecan hydrochloride (CPT-11) and a 14-day continuous infusion of etoposide in patients with lung cancer The therapy was judged as being unsuitable for further development because of toxicity (40) 9413 Phase II Phase II study of high-dose dexamethasone-based association in acute and delayed high-dose cisplatin-induced emesis Effectiveness of high-dose dexamethasone was demonstrated (41) 9507 Phase I/II Phase I/II trial of weekly cisplatin, etoposide, and irinotecan chemotherapy for metastatic lung cancer Effectiveness of the combined therapy was demonstrated (42) 9515 Phase II Randomized phase II trial of three intrapleural therapy regimens for the management of malignant pleural effusion in previously untreated non-small cell lung cancer Pleural adhesion therapy with OK-432 was shown to be effective for improving the 4-week pleural progression-free survival rate (43) 9605 Phase II A phase-II trial of dose-dense chemotherapy in patients with disseminated thymoma The outcome of CODE therapy was similar to that of the existing regimens (44) 9606 Phase II A phase II study of combined modality with CODE (cisplatin + vincristine + doxorubicin + etoposide) chemotherapy in patients with locally advanced thymoma The outcome of CODE therapy was similar to that of the existing regimens (45) 9608 Phase I/II Phase I/II study of escalating doses of nedaplatin in combination with irinotecan for advanced non-small-cell lung cancer The effectiveness/safety of nedaplatin + irinotecan therapy was demonstrated (46) 9811 Phase III A randomized controlled trial to evaluate the efficacy of intra-pericardial instillation of a sclerosing agent after pericardial drainage in patients with malignant pericardial effusion associated with lung cancer Superiority of bleomycin in terms of the primary endpoint (effusion failure-free survival) was not demonstrated (47) Open in new tab Table 4 Development of treatment strategies and supportive therapy for all lung cancers and rare chest malignancies JCOG No. . Phase, etc. . Study outline . Results . Reference . 9011 Phase III A randomized cross-over study of high-dose metoclopramide plus dexamethasone versus granisetron plus dexamethasone in patients receiving chemotherapy with high-dose cisplatin A higher antiemetic efficacy of granisetron + dexamethasone was demonstrated (39) 9408 Phase I/II Phase I study of a weekly infusion of irinotecan hydrochloride (CPT-11) and a 14-day continuous infusion of etoposide in patients with lung cancer The therapy was judged as being unsuitable for further development because of toxicity (40) 9413 Phase II Phase II study of high-dose dexamethasone-based association in acute and delayed high-dose cisplatin-induced emesis Effectiveness of high-dose dexamethasone was demonstrated (41) 9507 Phase I/II Phase I/II trial of weekly cisplatin, etoposide, and irinotecan chemotherapy for metastatic lung cancer Effectiveness of the combined therapy was demonstrated (42) 9515 Phase II Randomized phase II trial of three intrapleural therapy regimens for the management of malignant pleural effusion in previously untreated non-small cell lung cancer Pleural adhesion therapy with OK-432 was shown to be effective for improving the 4-week pleural progression-free survival rate (43) 9605 Phase II A phase-II trial of dose-dense chemotherapy in patients with disseminated thymoma The outcome of CODE therapy was similar to that of the existing regimens (44) 9606 Phase II A phase II study of combined modality with CODE (cisplatin + vincristine + doxorubicin + etoposide) chemotherapy in patients with locally advanced thymoma The outcome of CODE therapy was similar to that of the existing regimens (45) 9608 Phase I/II Phase I/II study of escalating doses of nedaplatin in combination with irinotecan for advanced non-small-cell lung cancer The effectiveness/safety of nedaplatin + irinotecan therapy was demonstrated (46) 9811 Phase III A randomized controlled trial to evaluate the efficacy of intra-pericardial instillation of a sclerosing agent after pericardial drainage in patients with malignant pericardial effusion associated with lung cancer Superiority of bleomycin in terms of the primary endpoint (effusion failure-free survival) was not demonstrated (47) JCOG No. . Phase, etc. . Study outline . Results . Reference . 9011 Phase III A randomized cross-over study of high-dose metoclopramide plus dexamethasone versus granisetron plus dexamethasone in patients receiving chemotherapy with high-dose cisplatin A higher antiemetic efficacy of granisetron + dexamethasone was demonstrated (39) 9408 Phase I/II Phase I study of a weekly infusion of irinotecan hydrochloride (CPT-11) and a 14-day continuous infusion of etoposide in patients with lung cancer The therapy was judged as being unsuitable for further development because of toxicity (40) 9413 Phase II Phase II study of high-dose dexamethasone-based association in acute and delayed high-dose cisplatin-induced emesis Effectiveness of high-dose dexamethasone was demonstrated (41) 9507 Phase I/II Phase I/II trial of weekly cisplatin, etoposide, and irinotecan chemotherapy for metastatic lung cancer Effectiveness of the combined therapy was demonstrated (42) 9515 Phase II Randomized phase II trial of three intrapleural therapy regimens for the management of malignant pleural effusion in previously untreated non-small cell lung cancer Pleural adhesion therapy with OK-432 was shown to be effective for improving the 4-week pleural progression-free survival rate (43) 9605 Phase II A phase-II trial of dose-dense chemotherapy in patients with disseminated thymoma The outcome of CODE therapy was similar to that of the existing regimens (44) 9606 Phase II A phase II study of combined modality with CODE (cisplatin + vincristine + doxorubicin + etoposide) chemotherapy in patients with locally advanced thymoma The outcome of CODE therapy was similar to that of the existing regimens (45) 9608 Phase I/II Phase I/II study of escalating doses of nedaplatin in combination with irinotecan for advanced non-small-cell lung cancer The effectiveness/safety of nedaplatin + irinotecan therapy was demonstrated (46) 9811 Phase III A randomized controlled trial to evaluate the efficacy of intra-pericardial instillation of a sclerosing agent after pericardial drainage in patients with malignant pericardial effusion associated with lung cancer Superiority of bleomycin in terms of the primary endpoint (effusion failure-free survival) was not demonstrated (47) Open in new tab Conclusions The JCOG Lung Cancer Study Group has been carrying out clinical studies, exploring new strategies of treatment, supportive therapies (antiemetics, etc.), etc., for a variety of cancers, including not only SCLC and NSCLC, but also rare chest tumours (represented by thymoma) and cancer-associated conditions (cancerous pericarditis, cancerous pleuritis, etc.). As immediate next steps, our group will focus on investigator-initiated clinical trials, Senshin-Iryo clinical trials and trials in collaboration with pharmaceutical companies. Under the rapidly changing environments surrounding clinical research, we shall continue to endeavor to carry out high-quality clinical studies to establish evidence to contribute to advances in cancer management. Reference 1. Fukuoka M , Furuse K , Saijo N , et al. Randomized trial of cyclophosphamide, doxorubicin, and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer . J Natl Cancer Inst 1991 ; 83 : 855 – 61 . Google Scholar Crossref Search ADS PubMed WorldCat 2. Ariyoshi Y , Fukuoka M , Furuse K , et al. Concurrent cisplatin-etoposide chemotherapy plus thoracic radiotherapy for limited-stage small cell lung cancer. Japanese lung cancer chemotherapy Group in Japanese Clinical Oncology Group . Jpn J Clin Oncol 1994 ; 24 : 275 – 81 . 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TI - History of Japan Clinical Oncology Group (JCOG) Lung Cancer Study Group
JF - Japanese Journal of Clinical Oncology
DO - 10.1093/jjco/hyaa031
DA - 2020-05-05
UR - https://www.deepdyve.com/lp/oxford-university-press/history-of-japan-clinical-oncology-group-jcog-lung-cancer-study-group-7ELuXNGS30
DP - DeepDyve
ER -