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

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Date publication

novembre 2011

Auteurs

Membres identifiés du Cancéropôle Est :
Pr FUMOLEAU Pierre, Dr RIOS Maria


Tous les auteurs :
Brain E, Levy C, Serin D, Roche H, Spielmann M, Delva R, Veyret C, Mauriac L, Rios M, Martin AL, Jimenez M, Asselain B, Gauthier M, Bonnetain F, Fumoleau P

Résumé

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.

Référence

Br J Cancer. 2011 Nov 8;105(10):1480-6