Tandem-cycle high-dose melphalan and cisplatin with peripheral blood progenitor cell support in patients with breast cancer and other malignancies

We evaluated the feasibility of tandem-cycle high-dose chemotherapy (HDCT) with cisplatin, melphalan, and peripheral blood progenitor cells (PBPCs). F ifty patients with high-risk primary (n = 17) or stage TV breast cancer (n = 29) or other malignancies (n = 4) received 2 cycles of intravenous melpha lan, 20 to 151.8 mg/m(2), and cisplatin, 200 mg/m(2), followed by granulocy te-macrophage colony-stimulating factor (GM-CSF) or G-CSE Starting at 40 mg /m(2) of melphalan, patients also received PBPCs. Delayed platelet recovery defined the maximum tolerated dose (MTD) for melphalan at 101.2 mg/m(2) pe r cycle. There were no treatment-related deaths. Cycle 2 was delivered at a median of 1.7 months after cycle 1; 72% of patients treated at the MTD rec eived both cycles. Cycle 2 was omitted when patients refused it or had dise ase progression or toxicities, primarily prolonged thrombocytopenia. Comple te response rates in stage TV breast cancer patients increased from 28% pre -HDCT to 55% after cycle 2. At a median follow-up of 4.6 years (range, 1.5- 8.1 years), 11 of 29 patients with stage IV breast carcinoma were alive wit h 5-year projected progression-free and overall survival rates of 19% (95% confidence interval [CI], 7%-41%) and 39% (95% CI, 20%-62%), respectively. Five-year projected progression-free and overall survival rates for patient s with stage TV breast cancer in complete response following HDCT versus al l others were 35% (95% CI, 15%-70%) versus 0% (P = .01) and 61% (95% CI, 35 %-91%) versus 10% (95% CI, 2%-60%) (P = .003; log-rank test), respectively. Estrogen-receptor positivity was predictive of reduced risk of progression (relative risk [RR], 0.25; 95% CI, 0.10-0.65; P = .003) and death (RR, 0.2 7; 95% CI, 0.10-0.72; P = .009) after adjusting for response status. Five-y ear projected relapse-free and overall survival rates were 71% (95% CI, 43% -96%) and 82% (95% CI, 56%-100%), respectively, for the 17 patients with hi gh-risk primary breast cancer. Tandem-cycle high-dose melphalan and cisplat in with PBPCs is feasible. Preliminary data suggest significant activity in selected patients with stage IV responding breast carcinoma.