PURPOSE: A three-arm randomized phase III trial in advanced colorectal cancer patients was designed to test whether substitution of an equivalent dose of (1) l-leucovorin or (2) oral leucovorin would more effectively potentiate fluorouracil (5-FU) than standard intravenous (I.V.) (d,l)-leucovorin. PATIENTS AND METHODS: A total of 926 chemotherapy-naive patients participated. Patients received one of three treatments: (A) intensive-course 5-FU plus l-leucovorin with I.V. leucovorin (Immunex Corp, Seattle, WA) at 100 mg/m2 and I.V. 5-FU at 370 mg/m2; (B) intensive-course 5-FU plus oral (d,l)-leucovorin with oral leucovarin at 125 mg/m2 on hours 0, 1, 2, and 3 (total dose, 500 mg/m2) followed by 5-FU 370 mg/m2 on hour 4; or (C) intensive-course 5-FU plus I.V. (d,l)-leucovorin with I.V. leucovorin 200 mg/m2 and 5-FU 370 mg/m2. Drugs were administered daily for 5 consecutive days. Courses were repeated at 4 and 8 weeks, and every 5 weeks thereafter. Dosage was reduced for neutropenia, thrombocytopenia, diarrhea, stomatitis, and dermatitis. RESULTS: Of 926 eligible patients, 756 have died. The overall response rate for patients with measurable disease was 32% (165 of 514). There were no differences between regimens in response rates (arm A, 28% [47 of 140]; arm B, 34% [60 of 174]; and arm C, 34% [58 of 170]) or in survival. There have been nine possible chemotherapy-related fatalities. Grade III to IV toxic effects did not differ appreciably by arm and included stomatitis (12% to 14%), diarrhea (15% to 19%), nausea (7% to 9%), and vomiting (6% to 8%). CONCLUSION: There was no difference in response, survival, or toxicity between these three different leucovorin formulations combined with 5-FU.
RCT Entities:
PURPOSE: A three-arm randomized phase III trial in advanced colorectal cancerpatients was designed to test whether substitution of an equivalent dose of (1) l-leucovorin or (2) oral leucovorin would more effectively potentiate fluorouracil (5-FU) than standard intravenous (I.V.) (d,l)-leucovorin. PATIENTS AND METHODS: A total of 926 chemotherapy-naive patients participated. Patients received one of three treatments: (A) intensive-course 5-FU plus l-leucovorin with I.V. leucovorin (Immunex Corp, Seattle, WA) at 100 mg/m2 and I.V. 5-FU at 370 mg/m2; (B) intensive-course 5-FU plus oral (d,l)-leucovorin with oral leucovarin at 125 mg/m2 on hours 0, 1, 2, and 3 (total dose, 500 mg/m2) followed by 5-FU 370 mg/m2 on hour 4; or (C) intensive-course 5-FU plus I.V. (d,l)-leucovorin with I.V. leucovorin 200 mg/m2 and 5-FU 370 mg/m2. Drugs were administered daily for 5 consecutive days. Courses were repeated at 4 and 8 weeks, and every 5 weeks thereafter. Dosage was reduced for neutropenia, thrombocytopenia, diarrhea, stomatitis, and dermatitis. RESULTS: Of 926 eligible patients, 756 have died. The overall response rate for patients with measurable disease was 32% (165 of 514). There were no differences between regimens in response rates (arm A, 28% [47 of 140]; arm B, 34% [60 of 174]; and arm C, 34% [58 of 170]) or in survival. There have been nine possible chemotherapy-related fatalities. Grade III to IV toxic effects did not differ appreciably by arm and included stomatitis (12% to 14%), diarrhea (15% to 19%), nausea (7% to 9%), and vomiting (6% to 8%). CONCLUSION: There was no difference in response, survival, or toxicity between these three different leucovorin formulations combined with 5-FU.
Authors: Qiang Zhang; Boris Freidlin; Edward L Korn; Susan Halabi; Sumithra Mandrekar; James J Dignam Journal: Clin Trials Date: 2016-09-22 Impact factor: 2.486
Authors: Kenneth L Kehl; Stacy W Gray; Benjamin Kim; Katherine L Kahn; David Haggstrom; Maryse Roudier; Nancy L Keating Journal: J Oncol Pract Date: 2014-12-30 Impact factor: 3.840