JNCI: Journal of the National Cancer Institute

doi: 10.1093/jnci/80.1.21pmid: 3276900

Abstract Information is presented from 555 patients with Dukes B and C rectal cancers treated by curative resection who were entered into the National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol R-01 between November 1977 and October 1986. Their average time on study was 64.1 months. The patients were randomized to receive no further treatment (184 patients), postoperative adjuvant chemotherapy with 5-fluorouracil, semustine, and vincristine (MOF) (187 patients), or postoperative radiation therapy (184 patients). The chemotherapy group, when compared with the group treated by surgery alone, demonstrated an overall improvement in disease-free survival (P = .006) and in survival (P = .05). Employing the proportional hazards model, a global test was used to determine the presence of treatment interactions. Investigation of stratification variables employed in this study indicated that sex, and to a lesser extent age and Dukes stage, made individual contributions to the disease-free survival and the survival benefit from chemotherapy. When evaluated according to sex, the benefit for chemotherapy at 5 years, both in disease-free survival (29% vs. 47%; P < .001; relative odds, 2.00) and in survival (37% vs. 60%; P = .001; relative odds, 1.93), was restricted to males. When males were tested for age trend with the use of a logistic regression analysis, chemotherapy was found to be more advantageous in younger patients. When the group receiving postoperative radiation (4,600–4,700 rad in 26–27 fractions; 5, 100–5, 300 rad maximum at the perineum) was compared to the group treated only by surgery, there was an overall reduction in local-regional recurrence from 25% to 16% (P = .06). No significant benefit in overall disease-free survival (P = .4) or survival (P =.7) from the use of radiation has been demonstrated. The global test for interaction to identify heterogeneity of response to radiation within subsets of patients was not significant. In conclusion, this investigation has demonstrated a benefit from adjuvant chemotherapy (MOF) for the management of rectal cancer. The observed advantage was restricted to males. Postoperative radiation therapy reduced the incidence of local-regional recurrence, but it failed to affect overall disease-free survival and survival. [J Natl Cancer Inst 1988; 80: 21–29] This content is only available as a PDF. Author notes 2Supported by Public Health Service grant CA-34212 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services; and by grant RC-13 from the American Cancer Society. Other NSABP investigators include: D. Prager (Allentown Hospital, Allentown, PA); M. Feldman (Boston University, Boston, MA); J. Terz (City of Hope Medical Center, Duarte, CA); W. Kraybill (Ellis Fischel State Cancer Hospital, Columbia, MO); J. Evans (Geisinger Medical Center, Danville, PA); A. Robidoux (Hotel-Dieu, Montreal, PQ, Canada); R. Margolese/Philip Gorden (Jewish General Hospital, Montreal, PQ, Canada; A.Glass (Kaiser Permanente, Portland, OR); H. Wold (Letterman Army Medical Center, San Francisco, CA); I.Coln (Louisiana State University, New Orleans, LA); D.Bowman (Manitoba Cancer Foundation, Winnipeg, MB, Canada); W.Lawrence (Medical College of Virginia, Richmond, VA); J. Guzik (Naval Hospital, san Diego, CA); H. Lerner (Pennysylania Hospital, Philodelphia, PA); H.Shibatal Marvin Wexler (Royal Victoria Hospital, Montreal, PQ, Canada); R.PoissonlS. Legault-Possion (St. Luc Hospital, Montreal, PQ, Canada); J. Keyserlingk (St. Mary's Hospital Center, Montreal, PQ, Canada); J. Berry (Tom Baker Cancer Centre, Calgary, AB, Canada); C. Sutherland (Tulane University, New Orleans, LA); B. Fisher (University of Pittsburgh, Pittsburghm PA); A. Cruz (University of Texas, San Antonio, TX). 4The contribution of Janet Shepherd in the preparation of this manuscript is acknowledged. © Oxford University Press

doi: 10.1093/jnci/80.1.30pmid: 3276901

Abstract Data are presented from 1,166 patients with Dukes B and C carcinoma of the colon who were entered into the National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol C-01 between November 1977 and February 1983. Patients were randomized to one of three therapeutic categories: 1) no further treatment following curative resection (394 patients); 2) postoperative chemotherapy consisting of 5-fluorouracil, semustine, and vincristine (379 patients); or 3) postoperative BCG (393 patients). The average time on study was 77.3 months. A comparison between patients receiving postoperative adjuvant chemotherapy and those treated with surgery alone indicated that there was an overall improvement in disease-free survival (P=.02) and survival (P=.05) in favor of the chemotherapy-treated group. At 5 years of follow-up, patients treated with surgery alone were at 1.29 times the risk of developing a treatment failure and at 1.31 times the likelihood of dying as were similar patients treated with combination adjuvant chemotherapy. Comparison of the BCG-treated group with the group treated with surgery alone indicated that there was no statistically significant difference in disease-free survival (P=.09). There was, however, a survival advantage in favor of the BCG-treated group (P=.03). At 5 years of follow-up, patients randomized to the surgery-alone arm were at 1.28 times the risk of dying as were similar patients treated with BCG. Further investigation disclosed that this survival advantage in favor of BCG was a result of a diminution in deaths that were non-cancer related. When analyses were conducted on which events not related to cancer recurrence were eliminated, the survival difference between the BCG and control groups became nonsignificant (P=.40); the cumulative odds at 5 years decreased from 1.28 to 1.10. The findings from this study are the first from a randomized prospective clinical trial to demonstrate that a significant disease-free survival and survival benefit can be achieved with postoperative adjuvant chemotherapy in patients with Dukes B and C carcinoma of the colon who have undergone curative resection. [J Natl Cancer Inst 1988;80:30–36] This content is only available as a PDF. Author notes 2Supported by Public Health Service grant CA-34212 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services; and by grant RC-13 from the American Cancer Society. Other NSABP investigators include: R. Sponzo (Albany Regional Cancer Center, Albany, NY); R. Rosen (Albert Einstein College of Medicine, Bronx, NY); D. Prager (Allentown Hospital, Allentown, PA); J. Spector (Berkshire Medical Center, Pittsfield, MA); B. Marchello (Billings Interhospital Oncology Project, Billings, MT); M. Feldman (Boston University, Boston, MA); J. M. Sterchi (Bowman Gray School of Medicine, Winston-Salem, NC); M. Morrow (Downstate Medical Center, Brooklyn, NY); J. Evans (Geisinger Medical Center, Danville, PA); D. State (Harbor General Hospital, Torrance, CA); A. Robidoux Hotel-Dieu, Montreal, PQ, Canada); R. Margolese (Jewish General Hospital, Montreal, PQ, Canada); A. Glass(Kaiser Permanente, Portland, OR); H. Wold (Letterman Army Medical Center, San Francisco, CA); I. Cohn (Louisiana State University, New Orleans, LA); D. Bowman (Manitoba Cancer Foundation, Winnipeg, MB, Canada); T. Banerjee (Marsh-field Clinic, Marshfield, WI); T. Wozniak (Medical Center of Delaware, Inc., Newark, DE); W. Lawrence (Medical College of Virginia, Richmond, VA); D. Plotkin (Memorial Cancer Research Foundation, Los Angeles, CA); R. Dresser (Michael Reese Hospital, Chicago, IL); N. Dimitrov (Michigan State University, E. Lansing, MI); M. Thirlwell (Montreal General Hospital, Montreal, PQ, Canada); J. Guzik (Naval Hospital, San Diego, CA); H. Lerner (Pennsylvania Hospital, Philadelphia, PA); H. Shibata/Marvin Wexler (Royal Victoria Hospital, Montreal, PQ, Canada); R. Poisson/S. Legault-Poisson (St. Luc Hospital, Montreal, PQ, Canada); P. Koontz (St. Luke's Hospital, Kansas City, MO); J. Keyserlingk (St. Mary's Hospital Center, Montreal, PQ, Canada); L. Mahoney (St. Michael's Hospital, Toronto, ON, Canada); M. Kemeny (St. Vincent's Hospital, New York, NY); J. Berry (Tom Baker Cancer Centre, Calgary, AB, Canada); C. Sutherland (Tulane University, New Orleans, LA); R. Oishi (University of Hawaii, Honolulu, HI); P. Jochimsen (University of Iowa, Iowa City, IA); E. G. Elias (University of Maryland, Baltimore, MD); B. Fisher (University of Pittsburgh, Pittsburgh, PA); A. Cruz (University of Texas, San Antonio, TX); J. Bledsoe (Washington Regional Medical Center, Rogers, AR); M. Tan (White Memorial Medical Center, Los Angeles, CA). © Oxford University Press