Different chemotherapy schedules in metastatic colorectal cancer: a response and survival analysis.

PURPOSE: To evaluate the response rate and overall survival (OS) of chemotherapy-naive patients with metastatic colorectal adenocarcinoma treated with 4 different chemotherapy regimens. PATIENTS AND METHODS: One hundred fifty-eight patients with metastatic colorectal cancer (CRC) were included in this prospective study. The treatment regimens were as follows: a) Intraarterial (i.a.) chemotherapy: 5-fluorouracil (5-FU) 600 mg/m(2)/day by 120 hour-infusion, mitomycin C 8 mg/m(2) day 1, and epirubicin 80 mg/m(2) day 5, every 3 weeks, b) Intravenous (i.v.) chronochemotherapy: 5-FU 800 mg/m(2) i.v. infusion during 18.00 h-06.00h, leucovorin (LV) 100 mg/m(2) i.v. infusion during 18.00h-06.00h; and cisplatin 20mg/m(2) i.v. infusion, during 10.00h-18.00 h, all given on days 1-5, every 3 weeks, c) Scheme: 5-FU 500 mg/m(2) i.v. bolus, days 1-5, vincristine 1.2 mg/m(2) i.v. bolus, day 1, CCNU 120 mg/m(2) per so (p.o.), day 5, every 3 weeks. Scheme I was used as control group, d) Scheme II: 5-FU 425 mg/m(2) i.v. bolus, days 1-5, and LV 50 mg/m(2) i.v. bolus, days 1-5, every 3 weeks. The patients received 3-26 cycles of chemotherapy. The results taken were compared using the Kaplan-Meier life-table method, logrank test, Cox proportional hazard model, and Cox model with time-dependent covariates. RESULTS: Nine (26%) out of 34 patients with i.a. chemotherapy achieved complete response (CR), 8 (24%) partial response (PR), and 11 (32%) stable disease (SD). In the group of 42 patients with chronochemotherapy 4 (10%) achieved CR, 15 (36%) PR and 12 (28%) SD. In the group of 61 patients with conventional treatment with 5-FU and LV (scheme II) no CR was achieved with 11 (18%) patients responding partially. In the control group of treatment (scheme I) with 21 patients PR was observed in 2 (10%) patients. Patients with i.a. chemotherapy and chronochemotherapy achieved a similar OS, which was better than OS of scheme II. The survival was worst with scheme I. CONCLUSION: I.a. chemotherapy and chronochemotherapy showed an almost equivalent efficacy in terms of response rates, which were clearly superior to those achieved by schemes I and II. Also, OS was significantly better in the patients treated with i.a. chemotherapy and chronochemotherapy compared to patients treated with scheme II. The worst survival was seen in scheme I patients.