Phase III study of mitomycin-C with protracted venous infusion or circadian-timed infusion of 5-fluorouracil in advanced colorectal carcinoma.

Abstract

The combination of protracted venous infusion (PVI) fluorouracil (5-FU) and mitomycin-C has previously been shown to be superior to PVI 5-FU alone in terms of response rate and failure-free survival. This study explores the effect of dose intensification by circadian timing of 5-FU in this combination on response, toxicity, and survival. Patients with advanced colorectal carcinoma were randomized to receive PVI 5-FU 300 mg/m2 daily or circadian-timed infusion (CTI) of 5-FU, beginning at 600 mg/m2 and subsequently reduced to 450 mg/m2, delivered as a flat-rate infusion from 10:15 PM to 9:45 AM. Both groups received mitomycin-C at a dose of 7 mg/m2 given every 6 weeks. From April 1996 to August 1998, 320 patients were randomized, including 263 with metastatic disease and 21 with circumferential margin involvement. The overall response rate for the PVI 5-FU group was 38%, compared with 30.3% for the CTI group (P = 0.176). There was no statistically significant difference in terms of failure-free survival (8.0 months vs. 9.9 months; P = 0.131) or overall survival (15.8 months vs. 16.3 months; P = 0.275) between the treatment groups. There were no differences in global quality of life. Grade 3/4 diarrhea occurred significantly more frequently with CTI 5-FU (6.5% vs. 19.8%; P < 0.001); a nonsignificant trend toward increased incidences of grade 3/4 infection and palmar plantar erythema were observed with CTI 5-FU. This study confirms the high response rate and overall survival figures for the combination of PVI 5-FU and mitomycin-C in colorectal cancer. However, dose intensification of 5-FU using a circadian-timed, flat-rate infusion did not lead to improved response or survival.

• Authors: Timothy J Price, Paul J Ross, Tamas Hickish, Diana Tait, Andy R Norman, Hugo E R Ford, Gary Middleton, Kate Sumpter, Mark Hill, Jacqui Oates, David Cunningham
• Journal: Clinical colorectal cancer (Clin Colorectal Cancer) Vol. 3 Issue 4 Pg. 235-42 (Feb 2004) ISSN: 1533-0028 [Print] United States
• PMID: 15025796 (Publication Type: Clinical Trial, Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)

Chemical References

• Antineoplastic Agents
• Mitomycin
• Fluorouracil

Topics

• Adenocarcinoma (drug therapy)
• Antineoplastic Agents (administration & dosage)
• Circadian Rhythm
• Colorectal Neoplasms (drug therapy)
• Fluorouracil (administration & dosage)
• Humans
• Infusions, Intravenous
• Mitomycin (administration & dosage)
• Survival Analysis
• Treatment Outcome