DOSE DENSE USE OF DOCETAXEL-100 NOT POSSIBLE

Br J Cancer. 2011 Oct 18. doi: 10.1038/bjc.2011.414. [Epub ahead of print]

High rate of extra-haematological toxicity compromises dose-dense sequential adjuvant chemotherapy for breast cancer.

Brain E, Levy C, Serin D, Roché H, Spielmann M, Delva R, Veyret C, Mauriac L, Rios M, Martin AL, Jimenez M, Asselain B, Gauthier M, Bonnetain F, Fumoleau P.

Source

Department of Medical Oncology, Institut Curie - Hôpital René Huguenin, 35 rue Dailly, 92210 Saint-Cloud, France.

Abstract

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