Randomized Trial of Adjuvant Therapy in Colon Carcinoma: 10-Year Results of NSABP Protocol C-01 Roy E. Smith, Linda Colangelo, H. Samuel Wieand, Mirsada Begovic, Norman Wolmark Affiliations of authors: NSABP Operations Center, Pittsburgh, PA (RES, NM); NSABP Biostatistical Center, Pittsburgh, PA (LC, HSW, MB) Correspondence to: Roy Smith, MD, National Surgical Adjuvant Breast and Bowel Project (NSABP), East Commons Professional Bldg., Four Allegheny Center—5th Floor, Pittsburgh, PA 15212-5234 (e-mail: melissa.wolfe@nsabp.org) Background: The National Surgical Adjuvant Breast and Bowel Project C-01 trial reported in 1988 that, for patients with adenocarcinoma of the colon, compared with surgery alone, 1) postoperative chemotherapy with 1-(2-chloroethyl)-3-(4-trans-methylcyclohexyl)-1-nitrosourea (i.e., MeCCNU or semustine), vincristine, and 5-fluorouracil was associated with better 5-year disease-free and overall survival and 2) postoperative immunotherapy with bacillus Calmette-Guérin was associated with better 5-year overall, but not disease-free, survival. We now provide a 10-year update of this trial. Methods: Between November 11, 1977, and February 28, 1983, 1166 patients with resected Dukes’ stage B and C adenocarcinoma of the colon were stratified by Dukes’ stage, sex, and age (<65 years or 65 years) and then randomly assigned to receive no further treatment (surgery alone; 394 patients), adjuvant chemotherapy (379 patients), or adjuvant immunotherapy (393 patients). Those eligible for follow-up included 375 (95.2%) patients in the surgery-alone group, 349 (92.1%) patients in the adjuvant-chemotherapy group, and 372 (94.7%) patients in the adjuvant-immunotherapy group. All statistical tests were two-sided. Results: No difference was observed between patients in the chemotherapy group and those in the surgery-alone group in 10-year disease-free survival (hazard ratio [HR] = 1.14, 95% confidence interval [CI] = 0.94 to 1.39;P = .17) or overall survival (HR = 1.12, 95% CI = 0.91 to 1.38; P= .27). Immunotherapy did not appear to prevent tumor relapse after 10 years (for surgery alone versus immunotherapy, relative risk [RR] = 0.99, 95% CI = 0.78 to 1.25; P = .93) but had a beneficial effect on 10-year overall survival (for surgery alone versus immunotherapy, RR = 1.27, 95% CI = 1.03 to 1.56; P = .02) that apparently results from a reduction in deaths associated with comorbidities in the immunotherapy group. Conclusion: The disease-free and overall survival benefit associated with chemotherapy in this patient population is of limited duration, disappearing after 10 years. Journal of the National Cancer Institute, Vol. 96, No. 15, 1128-1132, August 4, 2004 DOI: 10.1093/jnci/djh220 Ann's NOTE: A recent NSABP trial on Colon Cancer (comparing surgery alone, immunotherapy after surgery, or chemotherapy after surgery) produced the discovery that "for patients with Duke's stage B and C colon cancer, chemotherapy after surgery led to a statistically significant increase in 5-year disease-free and overall survival than surgery alone. At 10 years, however, the survival benefit of adjuvant chemotherapy had disappeared, the investigators now report in the August 4th Journal of the National Cancer Institute." Yet the conclusion: "Noting in an editorial that MOF is outdated, Dr. Jean Grem from the University of Nebraska Medical Center in Omaha favors adopting 3-year disease-free survival as a surrogate end point for 5-year overall survival in adjuvant colon cancer trials. This would allow "more timely completion of trials, and more rapid implementation of new trials testing promising new therapies." SO as I understand this, this doc is suggesting surrogate markers of success are acceptable even though over the long term the findings changed showing that all methods were equal. Since going through toxic chemotherapy to get the same result as surgery alone would be an unfair and TOXIC burden on the people involved, this conclusion does not seem correct or appropriate (it is NOT better or more useful to the patient). This discounts human suffering due to treatment. Suggesting that disease-free survival is good enough, is troublesome to me since most trial results tend to discount the price to the human beings involved. Great phrase often used - "no unexpected toxicities" but that does not reduce the reality of experiencing them, IMO. Comments? Ann F. Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.