Intensive dose-dense compared with conventionally scheduled preoperative chemotherapy for high-risk primary breast cancer

J Clin Oncol. 2009 Jun 20;27(18):2938-45. doi: 10.1200/JCO.2008.20.3133. Epub 2009 Apr 13.

Abstract

Purpose: To compare preoperative intense dose-dense (IDD) chemotherapy with conventionally scheduled preoperative chemotherapy in high-risk primary breast cancer (BC).

Patients and methods: In this randomized phase III trial a total of 668 eligible primary BC patients stratified for tumors > or = 3 cm (n = 567) or inflammatory BC (n = 101) were randomly assigned to receive concurrent preoperative epirubicin/paclitaxel every 3 weeks or dose-dense and dose-escalated sequential epirubicin followed by paclitaxel every 2 weeks. All patients received three cycles of cyclophosphamide, methotrexate, and fluorouracil chemotherapy after surgery.

Results: IDD treatment significantly improved pathologic complete response rate (18% v 10%; odds ratio [OR] 1.89; P = .008), disease-free survival (DFS; hazard ratio [HR], 0.71; P = .011), and overall survival (OS; HR, 0.83; P = .041) compared to epirubicin/paclitaxel. Patients with inflammatory BC had a particularly poor prognosis and did not appear to benefit from IDD therapy in this trial (DFS HR, 1.10; P = .739; OS HR, 1.25; P = .544). In contrast, patients with noninflammatory BC significantly benefited from IDD treatment (DFS HR, 0.65, P = .005; OS HR, 0.77, P = .013). Treatment effects in multivariate analysis were significant for noninflammatory BC (DFS HR, 0.65, P = .015; OS HR, 0.79, P = .034), but not for all patients (DFS HR, 0.76; P = .088; OS HR, 0.82; P = .059). IDD therapy was associated with significantly more nonhematologic toxicities, anemia, and thrombocytopenia, but with similar neutropenia and infection rates.

Conclusion: Our results support the efficacy and short-term safety of IDD as preoperative chemotherapy. IDD was less well tolerated compared to standard treatment, but improved clinical outcomes in patients with noninflammatory high-risk primary BC.

Publication types

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

MeSH terms

  • Antibiotics, Antineoplastic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / surgery
  • Disease-Free Survival
  • Drug Therapy, Combination
  • Epirubicin / administration & dosage*
  • Female
  • Humans
  • Middle Aged
  • Paclitaxel / administration & dosage*
  • Prognosis
  • Treatment Outcome

Substances

  • Antibiotics, Antineoplastic
  • Antineoplastic Agents, Phytogenic
  • Epirubicin
  • Paclitaxel