|Phase III||Treatment||Completed||18 to 70||NCI||NSABP-R-02|
I. Determine, in a randomized Phase III setting, whether the addition of radiotherapy to combination chemotherapy with MOF (methyl CCNU/vincristine/5-fluorouracil) or 5-fluorouracil plus high-dose leucovorin is more effective than chemotherapy alone in improving disease-free survival and overall survival in patients who have undergone potentially curative resection of Dukes' B or C adenocarcinoma of the rectum. II. Randomly compare the disease-free survival and overall survival of patients who have undergone potentially curable resection of Dukes' B or C adenocarcinoma of the rectum who receive adjuvant chemotherapy with MOF vs. 5-fluorouracil plus high-dose leucovorin.
Histologically documented Dukes' B or C adenocarcinoma of the rectum that has undergone potentially curative surgical resection To be classified as a rectal tumor, determination of distal extent of tumor must have required opening of pelvic peritoneum More than 1 synchronous rectal tumor allowed; classification based on histologic stage of more advanced primary tumor Direct extension into adjacent structures such as bladder, small intestine, or ovary permitted provided en bloc resection was effected and resection was potentially curative as confirmed histologically by tumor-free margins No multiple primary tumors involving both rectum and colon Intestinal obstruction allowed; preliminary or complementary colostomy permitted Free perforations (as manifested by free air in the abdomen) exclude, but walled-off perforations permitted Randomization must occur within 42 days postoperatively Postoperative complications permitted provided systemic therapy can begin 42 days postoperatively
Biologic therapy: No prior therapy Chemotherapy: No prior therapy Endocrine therapy: No prior therapy Radiotherapy: No prior therapy Surgery: Potentially curative resection required
Age: 18 to 70 Performance status: ECOG 0-2 Hematopoietic: WBC at least 4,000 Platelets at least 100,000 Hepatic: Bilirubin no greater than 1.5 mg/dl SGOT or SGPT no greater than 60 IU/ml GGTP no greater than 70 IU/ml in men and 30 IU/ml in women No hepatic disease that would preclude protocol therapy Renal: Creatinine no greater than 1.5 mg/dl No renal disease that would preclude protocol therapy Cardiovascular: No cardiovascular disease that would preclude protocol therapy Other: No other nonmalignant systemic disease that would preclude protocol therapy No previous or concomitant second malignancy except: Adequately treated nonmelanomatous skin cancer Adequately treated in situ cervical cancer No psychiatric or addictive disorders that would preclude informed consent No pregnant women CEA determination optional preoperatively, required postoperatively; results need not be known at randomization
750 patients will be accrued over about 5 years.
Randomized study. Male patients are randomized to all 4 arms, while females are randomized to Arms III and IV only. Arm I: 3-Drug Combination Chemotherapy. MOF: Methyl CCNU, MeCCNU, NSC-95441; Vincristine, VCR, NSC-67574; 5-Fluorouracil, 5-FU, NSC-19893. Arm II: 3-Drug Combination Chemotherapy plus Radiotherapy. MOF; plus pelvic irradiation using megavoltage photon beams with minimum energies of 4 MeV or Co60. Arm III: Single-agent Chemotherapy plus Biochemical Modulation. 5-FU; plus High-dose Leucovorin, Citrovorum Factor, CF, NSC-3590. Arm IV: Single-agent Chemotherapy plus Biochemical Modulation plus Radiotherapy. 5-FU; plus High-dose CF; plus pelvic irradiation as in Arm II.Published Results
Wolmark N, Wieand HS, Hyams DM, et al.: 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. J Natl Cancer Inst 92 (5): 388-96, 2000.[PUBMED Abstract]
Rockette H, Deutsch M, Petrelli N, et al.: Effect of postoperative radiation therapy (RTX) when used with adjuvant chemotherapy in Dukes' B and C rectal cancer: results from NSABP R-02. [Abstract] Proceedings of the American Society of Clinical Oncology 13: A-560, 193, 1994.Related Publications
Gunderson LL, Sargent DJ, Tepper JE, et al.: Impact of T and N stage and treatment on survival and relapse in adjuvant rectal cancer: a pooled analysis. J Clin Oncol 22 (10): 1785-96, 2004.[PUBMED Abstract]
Trial Lead Organizations
National Surgical Adjuvant Breast and Bowel Project
|Norman Wolmark, MD, Protocol chair|
Clinical Research Program - Northern California Cancer Center
|Robert Carlson, MD, Protocol chair|
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.