Radiation therapy and fluorouracil with or without semustine for the treatment of patients with surgical adjuvant adenocarcinoma of the rectum. Gastrointestinal Tumor Study Group.

PURPOSE To evaluate the contribution of semustine (MeCCNU) to adjuvant benefit, previously untreated patients with histologically proven adenocarcinoma of the rectum who had undergone curative resection were randomized to treatment with combination radiation therapy and fluorouracil (5-FU) followed by either 12 months of 5-FU and MeCCNU or 6 months of escalating 5-FU. PATIENTS AND METHODS Between March 1981 and November 1985, 210 patients were randomized by Gastrointestinal Tumor Study Group (GITSG) investigators. Subsequent to randomization, 11 (5%) patients (six treated with 5-FU and MeCCNU; five with escalating 5-FU) were found to be ineligible and are excluded from survival analyses. RESULTS About half the patients on each of the two treatment arms experienced at least one episode of severe or worse toxicity, and there was one treatment-related death on each arm. No episodes of leukemia have been reported. Median follow-up time for surviving patients is 5.8 years, and 3-year follow-up is available for all but five surviving patients. Recurrent disease has been reported in 54% (51 of 95) of 5-FU- and MeCCNU-treated patients compared with 43% (45 of 104) of escalating 5-FU-treated patients. Probability of 3-year disease-free survival for the two treatment cohorts is 54% and 68%, respectively. Ninety-one deaths have occurred: 46% (44 of 95) of 5-FU- and MeCCNU-treated patients and 45% (47 of 104) of escalating 5-FU-treated patients. Three-year postsurgery survival probabilities are 66% and 75%. CONCLUSION Substantial differences in survival or recurrence results between the two study arms are unlikely to be observed. We conclude that MeCCNU is not an essential component of effective postoperative combined modality treatment of adjuvant rectal cancer.

The Modulation of Fluorouracil With Leucovorin in Metastatic Colorectal Carcinoma

The authorship of the report "The Modulation of Fluorouracil With Leucovorin in Metastatic Colorectal Carcinoma: A Randomized Phase III Trial," published in the October 1989 issue (J Clin Oncol 7:1419–1426, 1989) should have read: "by the Gastrointestinal Tumor Study Group." The following appendix should also have appeared at the end of the report:

The modulation of fluorouracil with leucovorin in metastatic colorectal carcinoma: a prospective randomized phase III trial. Gastrointestinal Tumor Study Group.

A total of 343 patients with previously untreated metastatic measurable colorectal carcinoma were studied to evaluate the impact on toxicity, response, and survival of leucovorin-modulated fluorouracil (5-FU). A maximally tolerated intravenous bolus loading course regimen of 5-FU alone (500 mg/m2 x 5 days every 4 weeks with 25 mg/m2 escalation) was compared with a high-dose leucovorin regimen (600 mg/m2 of 5-FU with 500 mg/m2 of leucovorin weekly for 6 weeks with a 2-week rest) and with a similar low-dose leucovorin regimen (600 mg/m2 of 5-FU with 25 mg/m2 of leucovorin weekly for 6 weeks with a 2-week rest). The dose-limiting toxicity for the two 5-FU and leucovorin regimens was gastrointestinal, specifically diarrhea; severe diarrhea was seen frequently, and treatment-related toxicity was implicated in the demise of 11 of the patients (5%). Significant improvements in response rates were observed with a response rate of 33 of 109 (30.3%) on the high-dose leucovorin regimen (P less than .01 v control); 13 of 107 (12.1%) on the 5-FU control; and 21 of 112 (18.8%) on the low-dose leucovorin regimen. A trend toward longer survival in the 5-FU plus high-dose leucovorin regimen was observed. In this study, leucovorin was shown to significantly enhance the therapeutic effect of 5-FU in metastatic colorectal carcinoma.

Phase II studies of drug combinations in advanced pancreatic carcinoma: fluorouracil plus doxorubicin plus mitomycin C and two regimens of streptozotocin plus mitomycin C plus fluorouracil. The Gastrointestinal Tumor Study Group.

One hundred thirty-three patients with advanced pancreatic adenocarcinoma and measurable disease were treated with 5-fluorouracil (5-FU) plus doxorubicin plus mitomycin C (FAM), streptozotocin plus mitomycin C plus 5-FU (SMF) in the regimen originally reported, and streptozotocin plus mitomycin C plus 5-FU with 5-FU and streptozotocin administered in five-day courses. Respective response rates for all patients were 13%, 15%, and 14%, and for previously untreated patients, 14%, 14%, and 15%. Median survivals for all previously untreated patients range from 3 months (FAM) to 4 1/2 months (original SMF). Predominant toxic reactions were vomiting, leukopenia, and thrombocytopenia. Without evidence of greater therapeutic benefit, none of these regimens should be used in the routine treatment of advanced pancreatic carcinoma.