title: High-dose topotecan, melphalan, and cyclophosphamide (TMC) with stem cell support: a new regimen for the treatment of advanced ovarian cancer.
abstract: OBJECTIVE
  The goal of this study was to determine the optimal dose of topotecan when used in combination with high-dose melphalan and cyclophosphamide (TMC), and to assess the toxicity and efficacy of the regimen in patients with advanced ovarian cancer.
  
  
  METHODS
  Fifty-three patients with persistent or recurrent ovarian cancer were treated. Disease status at study entry included: platinum-sensitive recurrent disease (15 patients), platinum-resistant or refractory recurrent disease (15 patients), positive second-look surgery (16 patients), failure to achieve a primary clinical complete response (CR) (7 patients). Following stem cell mobilization and collection, patients were given cyclophosphamide 1 g/m(2)/day on Days -6, -5, -4; melphalan 70 mg/m(2)/day on Days -3, -2; and topotecan at escalating doses from 1.25 to 4.0 mg/m(2)/day on Days -6 to -2. Peripheral blood stem cells were infused on Day 0.
  
  
  RESULTS
  The optimal topotecan dose selected for future trials was 4.0 mg/m(2)/day x 5 days. The regimen had acceptable toxicity with no regimen-related death. Toxicity (Bearman toxicity criteria) was limited mostly to grade 1-2 mucositis and diarrhea. The overall response rate of patients with measurable or evaluable disease was 93%. Median survival has not yet been reached, but with a median follow up of 18 months (range: 11-37) 77% of patients are alive.
  
  
  CONCLUSIONS
  With a topotecan dose of 4.0 mg/m(2)/day x 5 days, the TMC regimen has acceptable toxicity and produces high response rates. In the setting of ovarian cancer, high-dose chemotherapy should be administered only as part of well-designed clinical trials. TMC should be considered a potential regimen for future randomized trials in patients with advanced ovarian cancer.
authors.affiliation: Department of Blood and Marrow Transplantation, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. mdonato@mdanderson.org
authors.forename: M L
authors.initials: ML
authors.lastname: Donato
authors.forename: D M
authors.initials: DM
authors.lastname: Gershenson
authors.forename: J T
authors.initials: JT
authors.lastname: Wharton
authors.forename: C M
authors.initials: CM
authors.lastname: Ippoliti
authors.forename: A S
authors.initials: AS
authors.lastname: Aleman
authors.forename: D
authors.initials: D
authors.lastname: Bodurka-Bevers
authors.forename: M W
authors.initials: MW
authors.lastname: Bevers
authors.forename: T W
authors.initials: TW
authors.lastname: Burke
authors.forename: C F
authors.initials: CF
authors.lastname: Levenback
authors.forename: J K
authors.initials: JK
authors.lastname: Wolf
authors.forename: R S
authors.initials: RS
authors.lastname: Freedman
authors.forename: R C
authors.initials: RC
authors.lastname: Bast
authors.forename: J L
authors.initials: JL
authors.lastname: Gajewski
authors.forename: R E
authors.initials: RE
authors.lastname: Champlin
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000628:therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000628:therapy; D015996:Survival Rate; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D019772:Topotecan; D003520:Cyclophosphamide; D008558:Melphalan