Background: Breast cancer patients with four or more positive axillary lymph nodes who are treated with conventional adjuvant therapy have a poor prognosis. In uncontrolled studies, high-dose chemotherapy produced much better results than conventional therapy. We compared the benefits of a single cycle of high-dose chemotherapy and the benefits of conventional chemotherapy in patients with high-risk breast cancer in a prospective, unblinded, randomized trial.
Methods: Between February 23, 1995, and June 29, 1999, 605 patients with breast cancer who had four or more positive lymph nodes were randomly assigned to treatment (307 to high-dose therapy and 298 to conventional therapy). The conventional chemotherapy regimen was four cycles of doxorubicin (75 mg/m2) followed by eight cycles of CMF (cyclophosphamide [600 mg/m2], methotrexate [50 mg/m2], and 5-fluorouracil [600 mg/m2]), all given intravenously on day 1 of a 21-day cycle. The high-dose regimen was four cycles of doxorubicin (75 mg/m2), followed by a single cycle of intermediate-dose cyclophosphamide (4000 mg/m2) supported by filgrastim (300 microg/day) for up to 10 days followed by high-dose cyclophosphamide (6000 mg/m2) and thiotepa (800 mg/m2). Peripheral blood progenitor cells were harvested by leukapheresis after treatment with cyclophosphamide and filgrastim and then re-infused after the high-dose cycle. Log-rank tests were used to compare survival rates. All statistical analyses were two-sided.
Results: At a median follow-up of 6 years, no statistically significant differences were detected between the arms in 5-year relapse-free survival (high-dose arm = 57%, 95% confidence interval [CI] = 51% to 63%; conventional-dose arm = 54%, 95% CI = 48% to 61% (P =.73) or in 5-year overall survival (high-dose arm = 62%, 95% CI = 56% to 68%; conventional-dose arm = 64%, 95% CI = 57% to 70%) (P =.38).
Conclusion: Autograft-supported, high-dose therapy is not superior to conventional chemotherapy in patients with breast cancer who have multiple involved lymph nodes. This conclusion should be viewed in the context of improving the success of conventional chemotherapy.