title: Phase I/II study of tandem cycles of high-dose chemotherapy followed by autologous hematopoietic stem cell support in women with advanced ovarian cancer.
abstract: The objectives of this study were to investigate the tolerability of a novel high-dose chemotherapy (HDC) regimen with peripheral blood progenitor cell (PBPC) support in patients with pretreated advanced ovarian cancer and to determine the maximum-tolerated dose (MTD) of topotecan in this setting. Advanced ovarian cancer patients previously treated with platinum-based first-line therapy were enrolled. After PBPC mobilization and harvesting, patients received three consecutive cycles of HDC with PBPC support. Cycle 1 was carboplatin area under the concentration curve 20 and paclitaxel 250 mg/m(2). Cycle 2 was topotecan starting at 5 mg/m(2), dose escalated in 2 mg/m(2) increments, and etoposide 600 mg/m(2). Cycle 3 was thiotepa 500 mg/m(2). After each cycle, PBPCs were infused. Granulocyte colony stimulating factor (5 microg/kg/day) was administered until neutrophil recovery occurred. Seventeen patients were enrolled; all were safety evaluable. The most common nonhematologic toxicity was grade 3 mucositis (44%). Engraftment of PBPCs was successful in all patients after each cycle, and no treatment-related deaths occurred. Of 14 patients with measurable disease, 5 (36%) had complete responses, 2 (14%) had partial responses, and 4 (29%) had stable disease. The median progression-free and overall survivals were 7 and 18 months, respectively. The MTD of topotecan was not reached. The tolerability and activity of this regimen in patients with advanced ovarian cancer warrant further investigation.
authors.affiliation: Division of Oncology, New York University, 160 East 32nd Street 2nd Floor, New York, NY 10016, USA. Amy.Tiersten@nyumc.org
authors.forename: A
authors.initials: A
authors.lastname: Tiersten
authors.forename: M
authors.initials: M
authors.lastname: Selleck
authors.forename: D H
authors.initials: DH
authors.lastname: Smith
authors.forename: I
authors.initials: I
authors.lastname: Wertheim
authors.forename: E
authors.initials: E
authors.lastname: Kaufman
authors.forename: D
authors.initials: D
authors.lastname: Hershman
authors.forename: L T
authors.initials: LT
authors.lastname: Vahdat
authors.forename: D G
authors.initials: DG
authors.lastname: Savage
authors.forename: R B
authors.initials: RB
authors.lastname: MacArthur
authors.forename: C
authors.initials: C
authors.lastname: Hesdorffer
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002277:Carcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D016879:Salvage Therapy; D016019:Survival Analysis; D013852:Thiotepa / Q000008:administration & dosage; D019772:Topotecan / Q000008:administration & dosage; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D019772:Topotecan; D013852:Thiotepa; D017239:Paclitaxel