TY - JOUR
AU - Boku,, Narikazu
AB - Abstract Background Malignant peritoneal mesothelioma (MPeM) is a rare cancer for which no standard systemic chemotherapy has been established. While cisplatin plus pemetrexed, the standard treatment for malignant pleural mesothelioma (MPlM), is usually used for MPeM, its efficacy remains unclear. Methods We retrospectively reviewed the medical charts of MPeM patients who had received cisplatin plus pemetrexed as first-line chemotherapy between January 2001 and July 2016 at the National Cancer Center Hospital. Patients received cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 on day1, repeated every 3 weeks until progressive disease, unacceptable toxicities or patient’s refusal to continue. Results A total of 29 MPeM patients received cisplatin plus pemetrexed. Median progression-free survival and overall survival were 7.1 months (95% CI: 4.8–9.3) and 15.4 months (95% CI: 9.5–21.2), respectively. Among 16 patients with measurable lesions, the response rate was 38%. Incidences of grade 3/4 leukopenia, neutropenia, anemia and thrombocytopenia were 21%, 17%, 14% and 3%, respectively. Non-hematological toxicities were mild, and there were no treatment-related deaths. Conclusions Cisplatin plus pemetrexed, showing consistent efficacy with MPlM, can be recommended as first-line treatment for unresectable MPeM patients. malignant peritoneal mesothelioma, chemotherapy, cisplatin, pemetrexed Introduction Mesothelioma is a malignant tumor derived from mesothelial cells of the pleura, peritoneum, and pericardium. Malignant peritoneal mesothelioma (MPeM) accounts for approximately 10 to 15 percent of all cases of mesothelioma (1). While the peritoneum is the second most frequent site of origin for mesothelioma, it has been reported that the incidence of MPeM in industrialized countries range only from 0.5 to 3 per million in men and from 0.2 to 2 per million in women (2). There is a strong relationship between asbestos exposure and the development of MPeM, especially in men (3). Diagnosis of MPeM is usually delayed until unspecific symptoms such as abdominal pain, vomiting, constipation and weight loss are experienced, and survival remains poor. For patients who can be predicted to achieve complete surgical cytoreduction, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are the most widely accepted treatment options. Otherwise, systemic chemotherapy is used for unresectable disease. However, a standard systemic chemotherapy for MPeM has not been established, and current treatment is largely extrapolated from the treatment strategy for malignant pleural mesothelioma (MPlM), for which cisplatin (CDDP) plus pemetrexed (PEM) combination chemotherapy has been established as the first-line standard treatment based upon a phase III clinical trial. It was reported that patients with MPlM who received CDDP plus PEM achieved a significantly superior overall survival compared with those receiving CDDP alone (12.1 versus 9.3 months, respectively; P = 0.020), longer time to disease progression (5.7 versus 3.9 months, P = 0.001), and a higher objective response rate (41% versus 17%, P < 0.001) (4). Because of the rarity of MPeM, there have been only a few reports evaluating the efficacy and safety of CDDP plus PEM as a first-line chemotherapy, and the number of cases in each report was small (5–11) In particular, few reports have been published regarding the treatment outcomes of CDDP plus PEM as first-line chemotherapy in Japanese population. Therefore, we retrospectively evaluated the cases of MPeM treated with CDDP plus PEM in our institution. Patients and methods Patients We retrospectively reviewed the medical records of patients with MPeM at National Cancer Center Hospital, Tokyo, Japan. The selection criteria for this study were: (1) histologically proven unresectable advanced or recurrent MPeM, (2) treatment with CDDP plus PEM between January 2001 and July 2016 as first-line chemotherapy, (3) Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–2, (4) adequate liver and bone marrow function such as absolute neutrophil count ≥ 1000/mm3, platelet ≥ 7.5 × 104/mm3, total bilirubin ≤ 1.5 mg/dl, aspartate transaminase ≤ 100 IU/l, alanine transaminase ≤ 100 IU/l, creatinine ≤ 1.5 mg/dl. We assessed the patient’s characteristics: age, sex, history of asbestos exposure, histology, amount of ascites, ECOG PS, prior surgery, metastatic sites and measurable lesions. The amount of ascites was categorized into three groups: mild ascites limited to either the upper abdomen or the pelvic cavity, massive ascites presenting continuously from the pelvic cavity to the upper abdomen; moderate ascites neither mild nor massive. Treatment Patients received intravenous infusions of CDDP 75 mg/m2 on day1, and PEM 500 mg/m2 on day 1, repeated every 3 weeks. Folic acid (0.5 g) was administered orally 1 week before the first dose of PEM, continued until the patient discontinued the treatment. Vitamin B12 (1000 mcg) was administered by intramuscular injection 1 to 2 weeks before the first dose of the treatment and repeated every 9 weeks until the discontinuation of the treatment. The treatment was discontinued on objective or clinically judged disease progression, unacceptable toxicity, or patient’s refusal to continue the chemotherapy. Evaluation Computed tomography (CT) was repeated every 8 weeks and tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Overall survival (OS) was calculated from the date of starting CDDP plus PEM to the date of death from any cause or censored at the last date confirming survival. Progression-free survival (PFS) was defined as duration from the date of starting CDDP plus PEM to objective or clinically judged disease progression or death. The survival curves of OS and PFS were calculated by the Kaplan–Meier method. Adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Analyses were performed by SPSS version 23.0 (SPSS, Inc., Chicago, IL, USA). This study was reviewed and approved by the Institutional Review Board in National Cancer Center Hospital in Japan, number 2017–229. Results Patient characteristics Between January 2001 and July 2016, 29 unresectable MPeM patients received CDDP plus PEM as the first-line treatment. Baseline characteristics are shown in Table 1. Their median age was 62 (range: 27–82) years, and 21 (73%) patients were male. History of asbestos exposure was recognized in 11 (38%) patients. ECOG PS was 0 in 10 (35%) and 1 in 18 (62%). Histological subtypes were epithelioid in 15 patients (52%), sarcomatoid in 2 (7%) and not available in 12 (41%). Nine (31%) patients had distant organ metastasis, and 16 (55%) patients had measurable lesions. Sixteen (55%) patients had massive ascites, 7 (24%) had moderate ascites and one (4%) had mild ascites. Table 1. Patient characteristics Baseline characteristics . N (%) . Age (range) 62 (27–82) Sex  Male 21 (72)  Female 8 (28) Asbestos exposure  Yes 11 (38)  No 17 (59)  Unknown 1 (3) Histology  Epithelioid 15 (52)  Sarcomatoid 2 (7)  Mixed 0  Unknown 12 (41) Amount of ascites  Massive 16 (55)  Moderate 7 (24)  Mild 1 (4)  None 5 (17) ECOG PS  0 10 (35)  1 18 (62)  2 1 (3) Prior surgery  Yes 5 (17)  No 24 (83) Distant metastases  Liver 5 (17)  Lymph Node 3 (10)  Lung 1 (3)  Pleural 1 (3)  Bone 1 (3) Measurable lesion  Yes 16 (55)  No 13 (45) Baseline characteristics . N (%) . Age (range) 62 (27–82) Sex  Male 21 (72)  Female 8 (28) Asbestos exposure  Yes 11 (38)  No 17 (59)  Unknown 1 (3) Histology  Epithelioid 15 (52)  Sarcomatoid 2 (7)  Mixed 0  Unknown 12 (41) Amount of ascites  Massive 16 (55)  Moderate 7 (24)  Mild 1 (4)  None 5 (17) ECOG PS  0 10 (35)  1 18 (62)  2 1 (3) Prior surgery  Yes 5 (17)  No 24 (83) Distant metastases  Liver 5 (17)  Lymph Node 3 (10)  Lung 1 (3)  Pleural 1 (3)  Bone 1 (3) Measurable lesion  Yes 16 (55)  No 13 (45) ECOG, Eastern Cooperative Oncology Group. PS, performance status. Open in new tab Table 1. Patient characteristics Baseline characteristics . N (%) . Age (range) 62 (27–82) Sex  Male 21 (72)  Female 8 (28) Asbestos exposure  Yes 11 (38)  No 17 (59)  Unknown 1 (3) Histology  Epithelioid 15 (52)  Sarcomatoid 2 (7)  Mixed 0  Unknown 12 (41) Amount of ascites  Massive 16 (55)  Moderate 7 (24)  Mild 1 (4)  None 5 (17) ECOG PS  0 10 (35)  1 18 (62)  2 1 (3) Prior surgery  Yes 5 (17)  No 24 (83) Distant metastases  Liver 5 (17)  Lymph Node 3 (10)  Lung 1 (3)  Pleural 1 (3)  Bone 1 (3) Measurable lesion  Yes 16 (55)  No 13 (45) Baseline characteristics . N (%) . Age (range) 62 (27–82) Sex  Male 21 (72)  Female 8 (28) Asbestos exposure  Yes 11 (38)  No 17 (59)  Unknown 1 (3) Histology  Epithelioid 15 (52)  Sarcomatoid 2 (7)  Mixed 0  Unknown 12 (41) Amount of ascites  Massive 16 (55)  Moderate 7 (24)  Mild 1 (4)  None 5 (17) ECOG PS  0 10 (35)  1 18 (62)  2 1 (3) Prior surgery  Yes 5 (17)  No 24 (83) Distant metastases  Liver 5 (17)  Lymph Node 3 (10)  Lung 1 (3)  Pleural 1 (3)  Bone 1 (3) Measurable lesion  Yes 16 (55)  No 13 (45) ECOG, Eastern Cooperative Oncology Group. PS, performance status. Open in new tab Treatment delivery and compliance The median course of CDDP plus PEM was 5 (range: 1–10). In six patients (21%), the initial dose of CDDP was reduced because of renal dysfunction (n = 3), poor general condition (n = 2) and older age (n = 1). During the treatment course, dose reduction was required in 11 patients (38%) due to adverse events such as renal dysfunction in 5 patients, neuropathy in 3, neutropenia in 2 and anorexia in 1. Chemotherapy was discontinued due to disease progression in 21 patients, while treatment was interrupted due to medical costs in 6 patients and due to grade 4 erythema multiforme in one patient. One patient was on the treatment at the cut-off date on 1st August 2017 (duration of treatment was 7.23 months at the cut-off date). Efficacy In 16 patients with measurable lesions, no complete response (CR), six partial responses (PR) and 7 stable disease (SD) were observed, resulting in response and disease control rates of 38% (6/16) and 81% (13/16), respectively (Table 2). All 29 patients were included in survival analysis. PFS and OS curves are shown in Figs 1 and 2, respectively. The median PFS was 7.1 months (95% CI, 4.8–9.3) and the median OS was 15.4 months (95% CI, 9.5–21.2). Table 2. Response of CDDP plus PEM Parameter . N (%) . Response  CR 0  PR 6 (38)  SD 7 (44)  PD 3 (19)  ORR 6 (38)  DCR 13 (82) Parameter . N (%) . Response  CR 0  PR 6 (38)  SD 7 (44)  PD 3 (19)  ORR 6 (38)  DCR 13 (82) CDDP cisplatin, PEM, pemetrexed. MPeM, malignant peritoneal mesothelioma. CR, complete response; PR, partial response. SD, stable disease; PD, progressive disease. ORR, overall response rate; DCR, disease control rate. Open in new tab Table 2. Response of CDDP plus PEM Parameter . N (%) . Response  CR 0  PR 6 (38)  SD 7 (44)  PD 3 (19)  ORR 6 (38)  DCR 13 (82) Parameter . N (%) . Response  CR 0  PR 6 (38)  SD 7 (44)  PD 3 (19)  ORR 6 (38)  DCR 13 (82) CDDP cisplatin, PEM, pemetrexed. MPeM, malignant peritoneal mesothelioma. CR, complete response; PR, partial response. SD, stable disease; PD, progressive disease. ORR, overall response rate; DCR, disease control rate. Open in new tab Figure 1. Open in new tabDownload slide Progression-free survival. Figure 1. Open in new tabDownload slide Progression-free survival. Figure 2. Open in new tabDownload slide Overall survival. Figure 2. Open in new tabDownload slide Overall survival. Safety Table 3 shows adverse events. As hematological toxicities, grade 3 to 4 leukopenia, neutropenia, anemia and thrombocytopenia were observed in 6 (21%), 5 (17%), 4 (14%) and 1 (3%) patients, respectively. Grade 3 anorexia was the most common non-hematological toxicity, seen in 6 (21%) patients, and grade 3 fatigue was seen in only one patient (3%). Grade 4 erythema multiform was seen in one patient. There was no treatment-related death. Table 3. Summary of adverse event Toxicity . Grade, N (%) . Any . 3/4 . Hematological toxicitity  Leukopenia 13 (45) 6 (21)  Neutropenia 14 (48) 5 (17)  Anemia 4 (14) 4 (14)  Thrombocytopenia 3 (10) 1 (3) Non-hematological toxicity  Nausea 19 (66) 0  Vomiting 7 (24) 0  Anorexia 25 (86) 6 (21)  Fatigue 14 (52) 1 (3)  Creatinine increased 14 (52) 0  Diarrhea 6 (21) 0  Constipation 10 (34) 0  Skin rash 3 (10) 1 (3)  Neurological disorder 5 (17) 0 Toxicity . Grade, N (%) . Any . 3/4 . Hematological toxicitity  Leukopenia 13 (45) 6 (21)  Neutropenia 14 (48) 5 (17)  Anemia 4 (14) 4 (14)  Thrombocytopenia 3 (10) 1 (3) Non-hematological toxicity  Nausea 19 (66) 0  Vomiting 7 (24) 0  Anorexia 25 (86) 6 (21)  Fatigue 14 (52) 1 (3)  Creatinine increased 14 (52) 0  Diarrhea 6 (21) 0  Constipation 10 (34) 0  Skin rash 3 (10) 1 (3)  Neurological disorder 5 (17) 0 Open in new tab Table 3. Summary of adverse event Toxicity . Grade, N (%) . Any . 3/4 . Hematological toxicitity  Leukopenia 13 (45) 6 (21)  Neutropenia 14 (48) 5 (17)  Anemia 4 (14) 4 (14)  Thrombocytopenia 3 (10) 1 (3) Non-hematological toxicity  Nausea 19 (66) 0  Vomiting 7 (24) 0  Anorexia 25 (86) 6 (21)  Fatigue 14 (52) 1 (3)  Creatinine increased 14 (52) 0  Diarrhea 6 (21) 0  Constipation 10 (34) 0  Skin rash 3 (10) 1 (3)  Neurological disorder 5 (17) 0 Toxicity . Grade, N (%) . Any . 3/4 . Hematological toxicitity  Leukopenia 13 (45) 6 (21)  Neutropenia 14 (48) 5 (17)  Anemia 4 (14) 4 (14)  Thrombocytopenia 3 (10) 1 (3) Non-hematological toxicity  Nausea 19 (66) 0  Vomiting 7 (24) 0  Anorexia 25 (86) 6 (21)  Fatigue 14 (52) 1 (3)  Creatinine increased 14 (52) 0  Diarrhea 6 (21) 0  Constipation 10 (34) 0  Skin rash 3 (10) 1 (3)  Neurological disorder 5 (17) 0 Open in new tab Subsequent chemotherapy After failure of CDDP plus PEM, 17 patients (59%) received second-line chemotherapy: gemcitabine (GEM) in 11 patients, carboplatin plus paclitaxel in 4, docetaxel in one and tremelimumab in one. Among the 11 patients who received GEM, response rate (RR) was 9% (1/11), the median PFS and OS calculating from initiating GEM were 3.0 months and 9.9 months, respectively. More than grade 3 toxicities of GEM were anemia in 2 patients (36%). There was no treatment-related death and no treatment discontinuation due to adverse events. Discussion This retrospective study evaluated the efficacy and safety of CDDP plus PEM as first-line chemotherapy for 29 Japanese patients with MPeM. The efficacy was modest with RR of 38%, a median PFS of 7.1 months and a median OS of 15.4 months, with acceptable toxicities. There are a few reports and several small case series reports published on PEM alone or in combination with CDDP (Table 4). Although all of them were retrospective studies, their results of efficacy were consistent including this study. Table 4. Summary of previous reports of PEM alone or in combination with CDDP for the patient with unresectable MPeM Author . Year . origin . regimen . N . RR (%) . DCR (%) . PFS/TTP (m) . OS (m) . 1 year survival (%) . Present study MPeM CDDP+PEM 29 38 81 7.1 15.4 41.4 Fujimoto E, et al (5) 2017 MPeM CDDP+PEM 24 45.8 91.7 11 15.8 58.3 Nakano M, et al (6) 2014 MPeM CDDP+PEM 6 33.3 100 7.2 13.1 NA Lainakis G, et al (7) 2011 MPeM CDDP+PEM 6 83 NA 9.5 24 NA Kim S T, et al (8) 2010 MPeM CDDP+PEM 14 35.7 71.4 4.4 20.1 NA Carteni G, et al (9) 2008 MPeM CDDP+PEM 30 20 80 NR NR 57.4 PEM 32 12.5 50 6.2 10.3 41.5 Janne PA, et al (10) 2005 MPeM CDDP+PEM 66 28.4 70 NA 13.1 66 PEM 26 19.2 73 NA 8.7 NA Reck M, et al (11) 2010 MPlM/MPeM CDDP+PEM 130 24 80 8.2 11.3 42 PEM 161 16 66 5.5 8.7 42 Author . Year . origin . regimen . N . RR (%) . DCR (%) . PFS/TTP (m) . OS (m) . 1 year survival (%) . Present study MPeM CDDP+PEM 29 38 81 7.1 15.4 41.4 Fujimoto E, et al (5) 2017 MPeM CDDP+PEM 24 45.8 91.7 11 15.8 58.3 Nakano M, et al (6) 2014 MPeM CDDP+PEM 6 33.3 100 7.2 13.1 NA Lainakis G, et al (7) 2011 MPeM CDDP+PEM 6 83 NA 9.5 24 NA Kim S T, et al (8) 2010 MPeM CDDP+PEM 14 35.7 71.4 4.4 20.1 NA Carteni G, et al (9) 2008 MPeM CDDP+PEM 30 20 80 NR NR 57.4 PEM 32 12.5 50 6.2 10.3 41.5 Janne PA, et al (10) 2005 MPeM CDDP+PEM 66 28.4 70 NA 13.1 66 PEM 26 19.2 73 NA 8.7 NA Reck M, et al (11) 2010 MPlM/MPeM CDDP+PEM 130 24 80 8.2 11.3 42 PEM 161 16 66 5.5 8.7 42 MPeM, malignant peritoneal mesothelioma; MPlM, malignant pleural mesothelioma; CDDP, cisplatin; PEM, pemetrexed; RR, response rate; DCR, disease control rate. PFS, progression-free survival; TTP, time to progression; OS, overall survival; m, month; NR, not reached; NA, not available. Open in new tab Table 4. Summary of previous reports of PEM alone or in combination with CDDP for the patient with unresectable MPeM Author . Year . origin . regimen . N . RR (%) . DCR (%) . PFS/TTP (m) . OS (m) . 1 year survival (%) . Present study MPeM CDDP+PEM 29 38 81 7.1 15.4 41.4 Fujimoto E, et al (5) 2017 MPeM CDDP+PEM 24 45.8 91.7 11 15.8 58.3 Nakano M, et al (6) 2014 MPeM CDDP+PEM 6 33.3 100 7.2 13.1 NA Lainakis G, et al (7) 2011 MPeM CDDP+PEM 6 83 NA 9.5 24 NA Kim S T, et al (8) 2010 MPeM CDDP+PEM 14 35.7 71.4 4.4 20.1 NA Carteni G, et al (9) 2008 MPeM CDDP+PEM 30 20 80 NR NR 57.4 PEM 32 12.5 50 6.2 10.3 41.5 Janne PA, et al (10) 2005 MPeM CDDP+PEM 66 28.4 70 NA 13.1 66 PEM 26 19.2 73 NA 8.7 NA Reck M, et al (11) 2010 MPlM/MPeM CDDP+PEM 130 24 80 8.2 11.3 42 PEM 161 16 66 5.5 8.7 42 Author . Year . origin . regimen . N . RR (%) . DCR (%) . PFS/TTP (m) . OS (m) . 1 year survival (%) . Present study MPeM CDDP+PEM 29 38 81 7.1 15.4 41.4 Fujimoto E, et al (5) 2017 MPeM CDDP+PEM 24 45.8 91.7 11 15.8 58.3 Nakano M, et al (6) 2014 MPeM CDDP+PEM 6 33.3 100 7.2 13.1 NA Lainakis G, et al (7) 2011 MPeM CDDP+PEM 6 83 NA 9.5 24 NA Kim S T, et al (8) 2010 MPeM CDDP+PEM 14 35.7 71.4 4.4 20.1 NA Carteni G, et al (9) 2008 MPeM CDDP+PEM 30 20 80 NR NR 57.4 PEM 32 12.5 50 6.2 10.3 41.5 Janne PA, et al (10) 2005 MPeM CDDP+PEM 66 28.4 70 NA 13.1 66 PEM 26 19.2 73 NA 8.7 NA Reck M, et al (11) 2010 MPlM/MPeM CDDP+PEM 130 24 80 8.2 11.3 42 PEM 161 16 66 5.5 8.7 42 MPeM, malignant peritoneal mesothelioma; MPlM, malignant pleural mesothelioma; CDDP, cisplatin; PEM, pemetrexed; RR, response rate; DCR, disease control rate. PFS, progression-free survival; TTP, time to progression; OS, overall survival; m, month; NR, not reached; NA, not available. Open in new tab In comparison with the efficacy of CDDP plus PEM for MPlM in the previous phase III trial (4), the results of this study seemed to be slightly better in terms of OS and PFS, and there was no difference in the response rates. Moreover, it was reported that the median OS was only 4 months among unresectable MPeM patients who did not receive chemotherapy (12). Therefore, it can be considered that CDDP plus PEM may be the most reasonable and optimal treatment for MPeM. As for second-line chemotherapy, GEM was the most commonly used regimen in this study. As far as we know, there are no reports that evaluate the efficacy and safety of second-line GEM in MPeM. Although its RR was poor, the median PFS and OS were 3.0 months and 9.9 months, respectively. While a survival benefit of second-line chemotherapy for MPeM is not clear, it has been reported that post-chemotherapy might improve the survival in MPIM. Patients with MPIM who received post-study chemotherapy (PSC) after failure of CDDP plus PEM showed longer survival than those who did not receive the PSC; the median OS was 15.3 months in patients with PSC vs. 9.8 months in non-PCS, [P < 0.001] (13). Based on this result, it is suggested that second-line GEM might have some clinical benefit with manageable toxicities. For MPIM, a survival benefit of adding bevacizumab was shown in a phase III trial comparing CDDP+PEM with/without bevacizumab. The median OS was 18.8 months in the CDDP+PEM with bevacizumab arm and 16.1 months in CDDP+PEM arm (P = 0.0167) (14). According to the results of the phase III trial for MPIM, it is suggested that bevacizumab may be a promising drug also for MPeM. Moreover, it was reported that pembrolizumab, an anti-PD-1 antibody, showed promising results in the phase 1b KEYNOTE-028 trial on PD-L1 positive MPIM patients (15). Recently, nivolumab, another anti-PD-1 antibody, was approved in Japan for MPlM patients who previously treated up to two regimens of chemotherapy including platinum plus PEM base on the promising results of phase II trial; with median follow-up 6.7 months, RR was 29.4%, median PFS was 6.1 months and median OS has not reached (16). Due to the rarity of the disease, it is difficult to conduct a randomized control trial targeting only MPeM. We propose that phase III trials for mesothelioma regardless of the origin, either pleura or peritoneum, should be conducted in order to develop new agents. This study has some limitations. First, this is a retrospective study at a single institution, and the number of patients was small. Second, the definition of unresectable disease is not so clear. We decided the indication of surgery and HIPEC through discussions with surgeons at the multidisciplinary conference, and almost all patients with MPeM were judged to be unresectable. Third, because there are no historical data before PEM was approved, the potential benefits of this combination regimen compared to other chemotherapy regimens to be evaluated. Finally, the AEs assessment was not uniform because the dose reduction was decided by each attending physician. In conclusion, CDDP plus PEM indicated consistent efficacy compared to previous reports, including the phase III study for MPlM. It is considered that CDDP plus PEM can be recommended as first-line treatment for patients with unresectable MPeM. Acknowledgments We would like to express our sincere thanks to all patients and investigators. Funding There was no funding. Conflict of interest statement All authors have nothing to disclose. References 1 Teta MJ , Mink PJ , Lau E , et al. US mesothelioma patterns 1973-2002: indicators of change and insights into background rates . Eur J Cancer Prev 2008 ; 17 : 525 – 534 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Boffetta P . Epidemiology of peritoneal mesothelioma: a review . Ann oncol. 2007 ; 18 : 985 – 990 . Google Scholar Crossref Search ADS PubMed WorldCat 3 Spirtas R , Heineman EF , Bernstein L , et al. Malignant mesothelioma: attributable risk of asbestos exposure . Occup Envirom Med 1994 ; 51 : 804 – 811 . Google Scholar Crossref Search ADS WorldCat 4 Vogelzang NJ , Rusthoven JJ , Symanowski J , et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma . J clin Oncol 2003 ; 21 : 2636 – 2644 . Google Scholar Crossref Search ADS PubMed WorldCat 5 Fujimoto E , Kijima T , Kuribayashi K , et al. First-line chemotherapy with pemetrexed plus cisplatin for malignant peritoneal mesothelioma . Expert Rev Anticancer Ther 2017 ; 17 : 865 – 872 . Google Scholar Crossref Search ADS PubMed WorldCat 6 Nakano M , Kusuba H , Makiyama A , et al. Pemetrexed combined with platinum-based chemotherapy for advanced malignant peritoneal mesothelioma: retrospective analysis of six cases . Anticancer Res. 2014 ; 34 : 215 – 220 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 7 Lainakis G , Zagouri F , Kastritis E , et al. Systemic chemotherapy with Pemetrexed and cisplatin for malignant mesothelioma: a single institution experience . Tumori. 2011 ; 97 : 25 – 29 . Google Scholar Crossref Search ADS PubMed WorldCat 8 Kim ST , Park JY , Lee J , et al. The efficacy of frontline platinum-based combination chemoptherapy in malignant peritoneal mesothelioma . Jpn J Clin Oncol 2010 ; 40 : 1031 – 1036 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Carteni G , Manegold C , Gracia M , et al. Malignant peritoneal mesothelioma - Results from the international expanded access program using pemetrexed alone or in combination with a platinaum agent . Lung Cancer 2009 ; 64 : 211 – 218 . Google Scholar Crossref Search ADS PubMed WorldCat 10 Janne PA , Wozniak AJ , Belani CP , et al. Open-label study of pemetrexed alone or in combination with cisplatin for the treatment of patients with peritoneal mesothelioma: outcomes of expanded access program . Clin Lung Cancer 2005 ; 7 : 40 – 46 . Google Scholar Crossref Search ADS PubMed WorldCat 11 Reck M , Stahel RA , Pawel JV , et al. Pemetrexed in the treatment of malignant mesothelioma: results from an expanded access program in Germany . Respir Med 2010 ; 104 : 142 – 148 . Google Scholar Crossref Search ADS PubMed WorldCat 12 Jennifer L B-D , Jon PF , Cecilia LY , et al. Mesothelioma in the United states: a Surveilance, Epidemiology, and End Results(SEER)-Medicare investigation of treatment patterns and overall survival . Clin Epidemiol 2016 ; 8 : 743 – 750 . Google Scholar Crossref Search ADS PubMed WorldCat 13 Manegolds C , Symanowski J , Gatzemeier U , et al. Second-line (post-study) chemotherapy received by patients treated in phase III trial of pemetrexed plus cisplatin alone in malignant pleural mesothelioma . Ann Oncol 2005 ; 16 : 923 – 927 . Google Scholar Crossref Search ADS PubMed WorldCat 14 Zalcman G , Mazieres J , Margery J , et al. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomized, controlled, open-label, phase 3 trial . Lancet Oncol 2016 ; 387 : 1405 – 1414 . Google Scholar Crossref Search ADS WorldCat 15 Alley EW , Lopez J , Santoro A , et al. Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial . Lancet Oncol 2017 ; 18 : 623 – 630 . Google Scholar Crossref Search ADS PubMed WorldCat 16 Goto Y , Okada M , Kijima T , et al. A phase II study of nivolumab: a mulicenter, open-label, single arm srudy in malignant pleural mesothelioma (MERIT) . J Thorac Oncol 2017 ; 12 : S1883 . Google Scholar Crossref Search ADS WorldCat Author notes Yusuke Nagata and Ryoichi Sawada authors contributed equally to this work. © The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
TI - Efficacy and safety of pemetrexed plus cisplatin as first-line chemotherapy in advanced malignant peritoneal mesothelioma
JF - Japanese Journal of Clinical Oncology
DO - 10.1093/jjco/hyz104
DA - 2019-12-18
UR - https://www.deepdyve.com/lp/oxford-university-press/efficacy-and-safety-of-pemetrexed-plus-cisplatin-as-first-line-0rtv0seirD
SP - 1004
VL - 49
IS - 11
DP - DeepDyve
ER -