Randomized trial of single compared with tandem high-dose chemotherapy followed by autologous stem-cell transplantation in patients with chemotherapy-sensitive metastatic breast cancer

Purpose: To compare progression-free survival between single and tandem high-dose chemotherapy (HDT) followed by autologous stem-cell transplantation in chemotherapy-sensitive metastatic breast cancer patients. Patients and Methods: Between February 1997 and June 2001, 187 patients with complete and partial remission were randomly assigned to receive either one or two cycles of HDT, consisting of thiotepa (125 mg/m²/d for 4 days), cyclophosphamide (1,500 mg/m²/d for 4 days), and carboplatin (200 mg/m²/d for 4 days), followed by autologous stem-cell transplantation. Results: One hundred seventy one of 187 randomly assigned patients completed first HDT, but only 52 of 85 completed the second HDT cycle in the tandem HDT arm. The rate of complete remission on an intent-to-treat-basis was 33% in the single-dose HDT arm and 37% in the tandem HDT arm (P = .48). The median progression-free survival times in single and tandem HDT arms were 9.4 and 11.2 months, respectively (one-sided P = .06; two one-sided P = .12), whereas median overall survival time tended to be greater after single versus tandem HDT (29 v 23.5 months, respectively; P = .4). In a multivariate analysis for progression-free survival, tandem HDT (hazard ratio [HR] = 0.71; 95% CI, 0.52 to 0.98; P = .03) and achievement of complete remission after induction chemotherapy (HR = 0.59; 95% CI, 0.37 to 0.96; P = .03) were factors for a better progression-free survival, whereas the factor of three or more sites of metastases (HR = 1.66; 95% CI, 1.12 to 2.47; P = .01) was associated with a worse progression-free survival. Conclusion: Despite a trend of improved progression-free survival, tandem HDT cannot be recommended for patients with chemotherapy-sensitive metastatic breast cancer because of a trend for shorter overall survival and higher toxicity compared with single HDT.