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

Br J Cancer. 2011 Nov 8;105(10):1480-6. doi: 10.1038/bjc.2011.414. Epub 2011 Oct 18.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Breast Neoplasms / drug therapy*
  • Chemotherapy, Adjuvant*
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Dose-Response Relationship, Drug
  • Epirubicin / administration & dosage
  • Epirubicin / adverse effects
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Humans
  • Middle Aged

Substances

  • Epirubicin
  • Cyclophosphamide
  • Fluorouracil

Supplementary concepts

  • FEC protocol