Randomized trial of postoperative Adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum : National Surgical Adjuvant breast and Bowel Project Protocol R-02

• Published in: JNCI : Journal of the National Cancer Institute Vol. 92; no. 5; pp. 388 - 396
• Main Authors: WOLMARK, N, WIEAND, H. S, PETRELLI, N. J, DEUTSCH, M, MAMOUNAS, E, WICKERHAM, D. L, FISHER, E. R, ROCKETTE, H, FISHER, B, HYAMS, D. M, COLANGELONI KOLAY, L, DIMITROV, V, ROMOND, E. H, WEXLER, M, PRAGER, D, CRUZ, A. B, GORDON, P. H
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 01.03.2000; Oxford Publishing Limited (England)
• Subjects: Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Cancer; Chemotherapy; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease-Free Survival; Drug Administration Schedule; Excretory system; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Fluorouracil - therapeutic use; Humans; Leucovorin - therapeutic use; Male; Medical sciences; Middle Aged; Neoplasm Staging; Pharmacology. Drug treatments; Radiation; Rectal Neoplasms - drug therapy; Rectal Neoplasms - pathology; Rectal Neoplasms - radiotherapy; Rectal Neoplasms - surgery; Semustine - administration & dosage; Sex Factors; Surgery; Survival Analysis; Therapy; Time Factors; Vincristine - administration & dosage; Antineoplastic agent; Rectal disease; Carcinoma; Nitrosoureas; Adjuvant treatment; Calcium folinate; Alkaloid; Randomization; Surgery; Intestinal disease; Clinical trial; Antimitotic; Fluorouracil; Human; Postoperative; Drug combination; Fluoropyrimidine derivatives; Malignant tumor; Radiotherapy; Vincristine; Alkylating agent; Chemotherapy; Treatment; Rectum; Digestive diseases; Pyrimidine derivatives; Semustine; Combined treatment; Fluorine Organic compounds; Comparative study
• ISSN: 0027-8874; 1460-2105; 1460-2105
• DOI: 10.1093/jnci/92.5.388

The conviction that postoperative radiotherapy and chemotherapy represent an acceptable standard of care for patients with Dukes' B (stage II) and Dukes' C (stage III) carcinoma of the rectum evolved in the absence of data from clinical trials designed to determine whether the addition of radiotherapy results in improved disease-free survival and overall survival. This study was carried out to address this issue. An additional aim was to determine whether leucovorin (LV)-modulated 5-fluorouracil (5-FU) is superior to the combination of 5-FU, semustine, and vincristine (MOF) in men. Eligible patients (n = 694) with Dukes' B or C carcinoma of the rectum were enrolled in National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol R-02 from September 1987 through December 1992 and were followed. They were randomly assigned to receive either postoperative adjuvant chemotherapy alone (n = 348) or chemotherapy with postoperative radiotherapy (n = 346). All female patients (n = 287) received 5-FU plus LV chemotherapy; male patients received either MOF (n = 207) or 5-FU plus LV (n = 200). Primary analyses were carried out by use of a stratified log-rank statistic; P values are two-sided. The average time on study for surviving patients is 93 months as of September 30, 1998. Postoperative radiotherapy resulted in no beneficial effect on disease-free survival (P =.90) or overall survival (P =.89), regardless of which chemotherapy was utilized, although it reduced the cumulative incidence of locoregional relapse from 13% to 8% at 5-year follow-up (P =.02). Male patients who received 5-FU plus LV demonstrated a statistically significant benefit in disease-free survival at 5 years compared with those who received MOF (55% versus 47%; P =.009) but not in 5-year overall survival (65% versus 62%; P =.17). The addition of postoperative radiation therapy to chemotherapy in Dukes' B and C rectal cancer did not alter the subsequent incidence of distant disease, although there was a reduction in locoregional relapse when compared with chemotherapy alone.