A feasibility study evaluating docetaxel-based sequential and combination regimens in the adjuvant therapy of node-positive breast cancer

Background and purpose: Docetaxel is an active agent in the treatment of me tastatic breast cancer. We evaluated the feasibility of docetaxel-based seq uential and combination regimens as adjuvant therapies for patients with no de-positive breast cancer. Patients and methods: Three consecutive groups of patients with node-positi ve breast cancer or locally-advanced disease, aged less than or equal to 70 years, received one of the following regimens: a) sequential A --> T --> C MF: doxorubicin 75 mg/m(2) q 3 weeks x 3, followed by docetaxel 100 mg/m(2) q 3 weeks x 3, followed by i.v. CMF days 1 + 8 q 4 weeks x 3; b) sequentia l accelerated A --> T --> CMF: A and T were administered at the same doses q 2 weeks; c) combination therapy: doxorubicin 50 mg/m(2) + docetaxel 75 mg /m(2) q 3 weeks x 4, followed by CMF x 4. When indicated, radiotherapy was administered during or after CMF, and tamoxifen started after the end of CM F. Results: Seventy-nine patients have been treated. Median age was 48 years. A 30% rate of early treatment discontinuation was observed in patients rece iving the sequential accelerated therapy (23% during A --> T), due principa lly to severe skin toxicity. Median relative dose-intensity was 100% in the three treatment arms. The incidence of G3-G4 major toxicities by treated p atients, was as follows: skin toxicity a: 5%; b: 27%; c: 0%; stomatitis a: 20%; b: 20%; c: 3%. The incidence of neutropenic fever was a: 30%; b: 13%; c: 48%. After a median follow-up of 18 months, no late toxicity has been re ported. Conclusions: The accelerated sequential A --> T --> CMF treatment is not fe asible due to an excess of skin toxicity. The sequential non accelerated an d the combination regimens are feasible and under evaluation in a phase III trial of adjuvant therapy.