Doxorubicin followed by docetaxel versus docetaxel followed by doxorubicin in the adjuvant treatment of node positive breast cancer: results of a feasibility study.

BACKGROUND: Doxorubicin (A) and Docetaxel (T) are amongst the most active agents in breast cancer treatment. The impact of drug sequencing is an issue still under evaluation. OBJECTIVE: To evaluate the feasibility and tolerability of two A and T-based sequential regimens, in which the sequence of drug administration was reversed. METHODS: The study included patients pts aged T-->CMF: Doxorubicin 75 mg/m2, i.v., day 1, q3wks x 3 cycles, followed by Docetaxel 100 mg/m2, i.v., day 1, q3wks x 3 cycles, followed by i.v. CMF days 1 and 8 q4wks x 3 cycles. 2) Sequential T-->A-->CMF: same doses for Doxorubicin and Docetaxel but reverse sequence of administration, followed by oral CMF (CPA 100 mg/m2, oral, days 1-14 + MTX 40 mg/m2, i.v., days 1 and 8 + 5FU 600 mg/m2, i.v., days 1 and 8, q4wks). An analysis of treatment administration and toxicity was performed for the first six cycles of CT, in the two treatment groups. RESULTS: Group 1 with 20 patients and group 2 with 14 patients were balanced in terms of patient and tumour characteristics. There was one early treatment discontinuation in each group due to toxicity (one allergic and one skin reaction to docetaxel). Median relative dose intensity was 100% for both drugs in both groups. The most relevant side effects were (overall incidence, group 1 vs group 2): Myalgia: 45% vs 72%; Arthralgia: 15% vs 57%; Skin: 35% vs 57%; Neurosensory: 55% vs 64%; Stomatitis 65% vs 36%; conjunctivitis 25% vs 57%; Neutropenic Fever 20% vs 21% and Fatigue 80% vs 93%. Grade 3/4 adverse events' rate was low in the two groups. CONCLUSIONS: 1) Both sequences were estimated feasible due to the optimal treatment administration and limited incidence of G3-G4 side effects. 2) The concomitant use of lenograstin might partially explain the reported incidence of myalgia and arthralgia. 3) No conclusion can be drawn on the most tolerable regimen due to the limited number of patients.