Seventy-nine patients with advanced, measurable, metastatic colorectal cancer previously unexposed to chemotherapy were randomly assigned to treatment with either fluorouracil (FUra) administered intravenously at a dose of 370 mg/m2/d for 5 days or the combination of FUra in the same dose and schedule with high-dose continuous infusion leucovorin calcium (500 mg/m2/d) beginning 24 hours before the first dose of FUra and continuing for 12 hours after the completion of FUra therapy. Patients whose disease progressed on treatment with FUra alone were, if eligible, crossed over to receive leucovorin and FUra. Three patients on the FUra plus leucovorin arm of the study were excluded from the analysis because they did not meet eligibility requirements. The treatment arms were well balanced for prognostic criteria including performance status, age, prior radiotherapy, distribution of metastatic sites, and on-study carcinoembryonic antigen (CEA), lactic dehydrogenase, and serum albumin. FUra plus leucovorin was superior to FUra alone for response (P = .0019) and for time to progression or death (log-rank, P = .045). Response rates were 16 of 36 (44%) versus five of 40 (13%), and median time to progression or death was 164 versus 120 days in the two arms of the trial, respectively. Overall survival, however, while longer in the FUra and leucovorin arm was not significantly so. An analysis of the toxicities experienced by the patients in the two treatment groups showed that, except for significantly more stomatitis in the leucovorin arm of the study, the side effects experienced by patients treated with either regimen were comparable. These results suggest that the efficacy of FUra in patients with advanced, measurable, metastatic colorectal cancer can be enhanced significantly by administration of a continuous high-dose infusion of leucovorin calcium.

No abstract

Encouraging results have recently been reported for studies using folinic acid in combination with 5-fluorouracil (5-FU) in the treatment of patients with gastrointestinal (GI) malignancies. Thirty-six patients with advanced colorectal cancer with unequivocal evidence of progression while treated with fluoropyrimidines were treated with a six-day continuous infusion of 500 mg/m2/d of folinic acid initiated 24 hours before a five-day course of 5-FU administered as an intravenous (IV) bolus of 370 mg/m2/d. An initial dose of 250 mg/m2/d of 5-FU was used in patients previously treated with ionizing radiation and/or a nitrosourea. Three objective partial responses were observed. The overall median duration of survival was 8.1 months. Toxicity was acceptable and not in excess of that expected for 5-FU alone.

From May 1972 until May 1976, 105 patients were entered on Central Oncology Group protocol 7230 to compare the combination of streptozotocin, tubercidin, and 5-fluorouracil (5-FU) versus 5-FU alone in the treatment of adenocarcinoma and islet cell carcinoma of the pancreas. Twenty-nine were not evaluable. Thirty-six evaluable cases received 5-FU, and 40 received the combination, with no significant difference in time to progression or survival. Toxicity in the two regimens was somewhat different but was essentially similar in magnitude. Results indicate no benefit in the treatment of adenocarcinoma of the pancreas with the three-drug combination over 5-FU alone. All of the islet cell tumor patients benefited from the combination by response or arrest of progression of disease. Further study should be directed toward the use of this combination in the treatment of functioning and non-functioning islet cell tumors of the pancreas.