High rate of extra-haematological toxicity compromises dose-dense sequential adjuvant chemotherapy for breast cancer
Background:A dose-dense strategy has been considered to improve results of adjuvant chemotherapy for breast cancer. This randomised phase II trial investigated the feasibility of this approach with sequential anthracyclines and taxanes-based chemotherapy.Methods:Patients with high-risk node-positive breast cancer were treated with three cycles of fluorouracil 500 mg m−2, epirubicin 100 mg m−2, cyclophosphamide 500 mg m−2 (FEC 100) followed by three cycles of docetaxel 100 mg m−2 delivered at 2-weekly intervals supported by primary prophylaxis with filgrastim. All patients were randomised to either uninterrupted treatment (arm A) or to have a 2-week additional period of rest between the FEC and docetaxel (arm B). The primary endpoint was the rate of success of chemotherapy delivery. Using a two-stage Fleming design, 120 patients were required with one interim analysis.Results:In March 2005, enrolment was stopped into arm A after the observation of severe skin toxicities. Following the planned interim analysis, the study was closed because of the high rate of grade 3/4 skin toxicities in both arms (arm A: 32.4% and arm B: 18.9%).Conclusion:Sequential dose-dense FEC 100 followed by docetaxel 100 mg m−2 is not feasible. Feasibility still depends largely on several factors including the choice of drugs, dosage and sequence of administration.