Doxorubicin followed by docetaxel versus docetaxel followed by doxorubicinin the adjuvant treatment of node positive breast cancer: Results of a feasibility study

Background: Doxorubicin (A) and Docetaxel (T) are amongst the most active a gents in breast cancel a treatment. The impact of drug sequencing is an iss ue still under evaluation. Objective: To evaluate the feasibility and toler ability of two A and T-based sequential regimens, in which the sequence of drug administration was reversed. Methods:The study included patients pts a ged less than or equal to 70 years, with operable node positive breast canc er: Two consecutive groups of patients received one of the following regime ns: 1) Sequential A --> T --> CMF: Doxorubicin 75 mg/m(2) iv day1, q3wks x 3 cycles, followed by Docetaxel 100 mg/m(2), i.v, day1, q3wk x 3 cycles, fo llowed by i.v CMF days I and 8 q4wks x 3 cycles. 2) Sequential T --> A --> CMF: same doses for Doxorubicin and Docetaxel but reverse sequence of admin istration followed by oral CMF (CPA 100mg/ m2, oral, 2 days 1-14 + MTX 40 m g/m(2) i.v, days 1 and 8 + 5FU 600 mg/ m(2), i.v, days 1 and 8 q4wks). An a nalysis of treatment administration and toxicity was performed for the firs t sh cycles of CT, in the two treatment groups. Results: Group 1 with 20 pa tients and group 2 with 14 patients were balanced in terms of patient and t umour characteristics. There was one early treatment discontinuation in eac h group due to toxicity tone 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)1 My algia: 45% vs 72%; Arthralgia: 15% vs 57%; Skin: 35% vs 57%; Neurosensory: 55% vs 64%; Stomatitis 65% vs 36%; conjunctivitis 25% vs 57%; Neutropenic F ever 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 feasib le due to the optimal treatment administration and limited incidence of G3- G4 side effects. 2) The concomitant use of lenograstin might partially expl ain the reported incidence of myalgia and arthralgia. 3) No conclusion can be drawn on the most tolerable regimen due to the limited number of patient s.