Doxorubicin in combination with fluorouracil and cyclophosphamide (i.v. FAC regimen, day 1, 21) versus methotrexate in combination with fluorouracil and cyclophosphamide (i.v. CMF regimen, day 1, 21) as adjuvant chemotherapy for operable breast cancer: a study by the GEICAM group.

BACKGROUND: The purpose of this study was to determine the relative efficacy of doxorubicin versus methotrexate in combination with intravenous cyclophosphamide and 5-fluorouracil (FAC versus CMF) as adjuvant chemotherapy for operable breast cancer. PATIENTS AND METHODS: Over a 4-year period, 985 women undergoing curative surgery for breast cancer (T1-3 N0-2 M0, stage I-IIIA, UICC) from nine hospitals were stratified with respect to axillary node involvement (node positive versus node negative) and randomized to receive either FAC (500/50/500/m(2)) every 3 weeks for six cycles or CMF (600/60/600/m(2)) every 3 weeks for six cycles. RESULTS: The relative dose intensities of FAC and CMF were 87% and 85% of planned doses, respectively. Unadjusted data indicated a non-significant trend towards better results with FAC. In the prospectively formed subset of node-negative patients, disease-free survival and overall survival were statistically superior in the FAC treatment arm (P = 0.041 and 0.034, respectively), but this advantage was not seen in the subset of node-positive patients, probably because of a difference in the percentage of patients with four or more positive nodes. Adjusting data for size of treatment effect and potential interactions (number of positive nodes, tumor size, treatment center), the overall relative risk (RR) of disease recurrence and death were significantly lower with FAC treatment (RR 1.2, P = 0.03, and RR 1.3, P = 0.05, respectively). This result was mainly due to the difference observed in the node-negative patient population. Toxicity was mild: FAC induced more alopecia, emesis, mucositis and cardiotoxicity; this last was of clinical concern, but was infrequent and manageable. CMF induced more conjunctivitis and weight gain. There were no toxic deaths. CONCLUSIONS: Doxorubicin in combination with day 1 i.v. cyclophosphamide and 5-fluorouracil is superior to methotrexate in combination with day 1 i.v. cyclophosphamide and 5-fluorouracil as adjuvant chemotherapy for operable breast cancer. A treatment effect is particularly evident in the node-negative patients. Although the clinical toxicity of FAC is greater than that of CMF, the levels were manageable and clinically acceptable.

Phase II study with iododoxorubicin in measurable advanced colorectal adenocarcinoma. Effective rescue using weekly high-dose 5-fluorouracil (WFU). Spanish Cooperative Group for Gastrointestinal Tumor Therapy (TTD), Work Group of SEOM (Spanish Medical Oncology Society).

AIMS AND BACKGROUND: To evaluate a new anthracycline 4'-iodo-4'-deoxydoxorubicin (I-DOX) in patients with measurable advanced colorectal adenocarcinoma in a phase II study. METHODS: We investigated therapeutic activity and toxicities associated with repeated courses of I-DOX 80 mg/m2 administered every 3 weeks. Eighteen patients entered the trial, all of them evaluable for response and toxicity. RESULTS: A total of 47 courses were administered. The median cumulative I-DOX dose was 238 mg/m2 (80-320). Myelosuppression, particularly leukopenia, was the most frequent and serious side effect associated with I-DOX treatment; World Health Organization (WHO) grade 3-4 leukopenia occurred in 4 patients (22%). No thrombocytopenia was observed except in 1 patient who presented WHO grade 4. Only 1 patient developed febrile neutropenia but recovered uneventfully. Overall, the I-DOX treatment was well tolerated. Grade 3-4 nausea/vomiting was observed in 2% of the cycles and no other severe toxicities were recorded. Echocardiography or multiple gated scan was performed before treatment and during follow-up in 14 patients to measure left ventricular ejection fraction (LVEF), and a decrease > 15% was detected in 3, including 1 whose LVEF fell below normal values (48%) (normal range > 49%). There were no cases of congestive heart failure or treatment-related deaths. No complete or partial response (PR) was observed. Twelve patients received weekly high-dose 5-fluorouracil (WFU) as rescue. Four patients had PR, 5 no change and 3 progressive disease (PD). The median time to PD of the whole group from study entry to failure after WFU was 30 weeks and the overall median survival was 11 months. CONCLUSIONS: As reported for other anthracyclines, I-DOX showed no activity in colorectal adenocarcinoma; however, the use of an investigational agent as front-line chemotherapy for colorectal adenocarcinoma does not compromise further response to 5-FU.