title: Tandem-cycle high-dose melphalan and cisplatin with peripheral blood progenitor cell support in patients with breast cancer and other malignancies.
abstract: We evaluated the feasibility of tandem-cycle high-dose chemotherapy (HDCT) with cisplatin, melphalan, and peripheral blood progenitor cells (PBPCs). Fifty patients with high-risk primary (n = 17) or stage IV breast cancer (n = 29) or other malignancies (n = 4) received 2 cycles of intravenous melphalan, 20 to 151.8 mg/m2, and cisplatin, 200 mg/m2, followed by granulocyte-macrophage colony-stimulating factor (GM-CSF) or G-CSF. Starting at 40 mg/m2 of melphalan, patients also received PBPCs. Delayed platelet recovery defined the maximum tolerated dose (MTD) for melphalan at 101.2 mg/m2 per 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 received both cycles. Cycle 2 was omitted when patients refused it or had disease progression or toxicities, primarily prolonged thrombocytopenia. Complete response rates in stage IV 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 with 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 patients with stage IV breast cancer in complete response following HDCT versus all 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, 0.27; 95% CI, 0.10-0.72; P = .009) after adjusting for response status. Five-year 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 high-risk primary breast cancer. Tandem-cycle high-dose melphalan and cisplatin with PBPCs is feasible. Preliminary data suggest significant activity in selected patients with stage IV responding breast carcinoma.
authors.affiliation: Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, California 91010-3000, USA. gsomlo@coh.org
authors.forename: G
authors.initials: G
authors.lastname: Somlo
authors.forename: W
authors.initials: W
authors.lastname: Chow
authors.forename: V
authors.initials: V
authors.lastname: Hamasaki
authors.forename: L
authors.initials: L
authors.lastname: Leong
authors.forename: K
authors.initials: K
authors.lastname: Margolin
authors.forename: R
authors.initials: R
authors.lastname: Morgan
authors.forename: I
authors.initials: I
authors.lastname: Sniecinski
authors.forename: P
authors.initials: P
authors.lastname: Frankel
authors.forename: D
authors.initials: D
authors.lastname: Reardon
authors.forename: E
authors.initials: E
authors.lastname: Longmate
authors.forename: J
authors.initials: J
authors.lastname: Raschko
authors.forename: S
authors.initials: S
authors.lastname: Shibata
authors.forename: M
authors.initials: M
authors.lastname: O'Donnell
authors.forename: E
authors.initials: E
authors.lastname: Smith
authors.forename: M
authors.initials: M
authors.lastname: Tetef
authors.forename: S
authors.initials: S
authors.lastname: Forman
authors.forename: Y
authors.initials: Y
authors.lastname: Yen
authors.forename: A
authors.initials: A
authors.lastname: Molina
authors.forename: H
authors.initials: H
authors.lastname: Doroshow
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000633:toxicity; D001943:Breast Neoplasms / Q000150:complications / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity; D018572:Disease-Free Survival; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D020714:Maximum Tolerated Dose; D008558:Melphalan / Q000008:administration & dosage / Q000633:toxicity; D008875:Middle Aged; D009367:Neoplasm Staging; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D002945:Cisplatin; D008558:Melphalan