Different chemotherapy schedules in metastatic colorectal cancer: a response and survival analysis.
OBJECTIVE
To evaluate the response rate and overall survival (OS) of chemotherapy-naïve patients with metastatic colorectal adenocarcinoma treated with 4 different chemotherapy regimens.


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.


CONCLUSIONS
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.
Kurteva
G
G
Department of Chemotherapy, National Center of Oncology, Sofia, Bulgaria.
Kurtev
P
P
Krusteva
E
E
Valerianova
Z
Z
Boyadjieva
L
L