Biweekly intensified ambulatory chronomodulated chemotherapy with oxaliplatin, fluorouracil, and leucovorin in patients with metastatic colorectal cancer.

PURPOSE: This study sought to determine the feasibility and antitumor efficacy of an intensified three-drug chronomodulated regimen with maximum delivery at 4:00 AM for fluorouracil (5-FU)-leucovorin (folinic acid [FA]) and at 4:00 PM for oxaliplatin (I-OHP). PATIENTS AND METHODS: Fifty patients with metastatic colorectal cancer were enrolled in the trial. The first treatment course consisted of daily administration of 5-FU (700 mg/m2/d), FA (300 mg/m2/d), and L-OHP (25 mg/m2/d) for 4 days with a multichannel programmable pump. Courses were repeated every 14 days, with 5-FU escalation by 100 mg/m2/d if toxicity was less than grade 2. RESULTS: World Health Organization (WHO)-modified grade 3 or 4 diarrhea (40% of patients and 7% of courses) or stomatitis (28% of patients and 4% of courses) or grade 2 cumulative peripheral sensitive neuropathy (28% of patients) were dose-limiting. Median 5-FU and L-OHP dose-intensities (DIs), were increased by 32% and 18%, respectively, as compared with our previous 5 days on-16 days off schedule. The overall objective response rate was 48% (95% confidence limits [CL], 34% to 62%), being 40% (24% to 57%) in 37 previously treated patients and 69% (48% to 90%) in 13 chemotherapy-naive patients. A 5-FU DI > 1,400 mg/m2/wk over four courses was associated with a near doubling of the response rate. Residual metastases were surgically removed in 13 patients (26%). Median progression-free survival and survival durations were 9.3 months (95% CL, 6.6 to 11.2) and 17.8 months (95% CL, 14.1 to 21.4), respectively. CONCLUSION: This highly effective fully ambulatory outpatient regimen deserves further testing in randomized trials both in chemotherapy-naive patients and before surgery to remove metastases.

Adjuvant treatment of node-positive breast cancer with cyclophosphamide, doxorubicin, fluorouracil, and vincristine versus cyclophosphamide, methotrexate, and fluorouracil: final report after a 16-year median follow-up duration.

PURPOSE: To determine the long-term impact on disease-free survival (DFS) and overall survival (OS) of adjuvant anthracycline-based chemotherapy, when prospectively compared by random allocation with standard cyclophosphamide, methotrexate, and fluorouracil (CMF) in node-positive (N+) breast cancer patients. PATIENTS AND METHODS: Two hundred forty-nine patients with N+ breast cancer, recruited from eight French cancer centers, were randomized to receive 12 monthly cycles of adjuvant chemotherapy, either CMF (n = 112) or doxorubicin, vincristine, cyclophosphamide, and fluorouracil (AVCF) (n = 136). All had a negative metastatic work-up before inclusion, which was stratified by accrual center, tumor stage (International Union Against Cancer [UICC]), and menopausal status. RESULTS: No severe adverse effect related to grade 4 (World Health Organization [WHO]) toxicity was observed. There was no difference in second primary tumor incidence between the two arms. The treatment given was 88% of planned for AVCF and 75% for CMF in both premenopausal and menopausal patients. With a median follow-up time of 16 years (range, 13 to 17), the OS and DFS rates are significantly longer in the AVCF arm (56% v 41% [P = .01] for OS, and 53% v 36% [P = .006] for DFS). These differences are significant, irrespective of tumor stage (T1 to T2 v T3 to T4), and remain positive in patients with or without postoperative locoregional radiotherapy (55% of cohort). When analyzed according to menopausal status, the differences remain significant only for premenopausal patients. CONCLUSION: This set of mature controlled data confirms the added value of anthracycline-based combination adjuvant therapy for N+ breast cancer patients when compared with CMF, with both regimens given for 1 year.