title: Paclitaxel-based high-dose chemotherapy with autologous stem cell rescue for relapsed germ cell cancer.
abstract: We evaluated the antitumor activity of tandem cycles of high-dose chemotherapy with autologous peripheral stem cell transplantation (aPSCT) in relapsed germ cell tumors by using high-dose paclitaxel, carboplatin, etoposide, and ifosfamide. Thirty-three patients were entered, and 31 underwent protocol therapy. Paclitaxel 350 mg/m2 (5 patients) or 425 mg/m2 (26 patients) by 24-hour continuous intravenous infusion was followed by 3 daily doses of carboplatin and either etoposide (cycle 1) or ifosfamide/mesna (cycle 2). The carboplatin dose had a calculated area under the curve of 7 mg-min/mL, and the daily dose of etoposide was 20 mg/kg (cycle 1). Ifosfamide 3 g/m2/d for 3 days (with mesna uroprotection) was substituted for etoposide in cycle 2. Each cycle was supported by granulocyte colony-stimulating factor-mobilized peripheral blood stem cells. Thirty-one patients were evaluable for response, toxicity, and long-term disease control. Two patients did not undergo aPSCT because of rapid disease progression. Nineteen patients received both cycles of aPSCT, 8 progressed after cycle 1, 3 refused the second cycle, and 1 died of fungal infection during cycle 1. Twelve patients remain relapse free at a median of 67 months from the initiation of therapy. Whereas the International Germ Cell Cancer Collaborative Group category at the time of initial diagnosis did not seem to predict outcome, the patient's probability of achieving durable remission was significantly associated with the Beyer prognostic score at the time of protocol entry. Regimens containing the most active agents in relapsed nonseminomatous germ cell tumors, including high-dose paclitaxel, are well tolerated and have promising activity even in patients with poor-risk features who do not achieve durable remissions with standard therapy. The Beyer prognostic system is a valuable predictor for patients undergoing aPSCT.
authors.affiliation: Department of Medical Oncology, City of Hope National Medical Center, Duarte, California 91010, USA. kmargolin@coh.org
authors.forename: Kim A
authors.initials: KA
authors.lastname: Margolin
authors.forename: James H
authors.initials: JH
authors.lastname: Doroshow
authors.forename: Paul
authors.initials: P
authors.lastname: Frankel
authors.forename: Warren
authors.initials: W
authors.lastname: Chow
authors.forename: Lucille A
authors.initials: LA
authors.lastname: Leong
authors.forename: Dean
authors.initials: D
authors.lastname: Lim
authors.forename: Mark
authors.initials: M
authors.lastname: McNamara
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Morgan
authors.forename: Stephen
authors.initials: S
authors.lastname: Shibata
authors.forename: George
authors.initials: G
authors.lastname: Somlo
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Twardowski
authors.forename: Yun
authors.initials: Y
authors.lastname: Yen
authors.forename: Neil
authors.initials: N
authors.lastname: Kogut
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schriber
authors.forename: Joseph
authors.initials: J
authors.lastname: Alvarnas
authors.forename: Susan
authors.initials: S
authors.lastname: Stalter
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000401:mortality / Q000628:therapy*; D017239:Paclitaxel / Q000008:administration & dosage*; D036102:Peripheral Blood Stem Cell Transplantation; D011379:Prognosis; D016879:Salvage Therapy / Q000379:methods; D016019:Survival Analysis; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D005047:Etoposide; D016190:Carboplatin; D017239:Paclitaxel; D007069:Ifosfamide