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Multicycle Dose-Intensive Chemotherapy for Women With High-Risk Primary Breast Cancer: Results of International Breast Cancer Study Group Trial 15-95

From the International Breast Cancer Study Group. Appendix lists the names and affiliations of the writing committee, and participants and authors of Trial 15-95.

Address reprint requests to Russell Basser, CSL Ltd, 45 Poplar Rd,Parkville, Vic 3052, Australia; e-mail: russell.basser{at}csl.com.au

Purpose: To compare adjuvant dose-intensive epirubicin and cyclophosphamide chemotherapy administered with filgrastim and progenitor cell support (DI-EC) with standard-dose anthracycline-based chemotherapy (SD-CT) for patients with early-stage breast cancer and a high risk of relapse, defined as stage II disease with 10 or more positive axillary nodes; or an estrogen receptor–negative or stage III tumor with five or more positive axillary nodes.

Patients and Methods: Three hundred forty-four patients were randomized after surgery to receive seven cycles of SD-CT over 22 weeks, or three cycles of DI-EC (epirubicin 200 mg/m² plus cyclophosphamide 4 gm/m² with filgrastim and progenitor cell support) over 6 weeks. All patients were assigned tamoxifen at the completion of chemotherapy. The primary end point was disease-free survival (DFS).

Results: After a median follow-up of 5.8 years (range, 3 to 8.4 years), 188 DFS events had occurred (DI-EC, 86 events; SD-CT, 102 events). The 5-year DFS was 52% for DI-EC and 43% for SD-CT, with hazard ratio of DI-EC compared with SD-CT of 0.77 (95% CI, 0.58 to 1.02; P = .07). The 5-year overall survival was 70% for DI-EC and 61% for SD-CT, with a hazard ratio of 0.79 (95% CI, 0.56 to 1.11; P = .17). There were eight cases (5%) of anthracycline-induced cardiomyopathy (two fatal) among those who received DI-EC. Women with hormone receptor–positive tumors benefited significantly from DI-EC.

Conclusion: There was a trend in favor of DI-EC with respect to disease-free survival. A larger trial or meta-analysis will be required to reveal the true effect of dose-intensive therapy.

Supported by funded in part by: Swiss Group for Clinical Cancer Research, Frontier Science and Technology Research Foundation, The Cancer Council Australia, Australian New Zealand Breast Cancer Trials Group, National Cancer Institute (CA-75362), Swedish Cancer Society, Foundation for Clinical Research of Eastern Switzerland. Further support provided by Amgen, Australia, and Pharmacia (now Pfizer), Australia, and Grants from the National Health and Medical Research Council of Australia.

Presented at the American Society of Clinical Oncology Meeting, Chicago, IL, May 31-June 3, 2003.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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