title: Phase I trial of multiple cycles of high-dose chemotherapy supported by autologous peripheral-blood stem cells.
abstract: OBJECTIVE
  To determine the safety and feasibility of delivering multiple cycles of front-line high-dose carboplatin and paclitaxel with hematopoietic peripheral-blood stem cell (PBSC) support.
  
  
  METHODS
  Patients were required to have a malignant solid tumor for which they had received no prior chemotherapy. Mobilization of PBSC was achieved with cyclophosphamide, etoposide, and granulocyte-macrophage colony-stimulating factor (GM-CSF). After one cycle of conventional-dose carboplatin and cyclophosphamide with GM-CSF, patients received multiple cycles of high-dose carboplatin (area under the concentration-time curve [AUC], 12 to 20) and paclitaxel (250 mg/m(2)) with PBSC and GM-CSF repeated every 28 days.
  
  
  RESULTS
  Twenty-four of 28 patients were assessable for toxicity and clinical outcome. Dose-limiting toxicities were dehydration, diarrhea, and electrolyte imbalances. The maximum-tolerated dose of carboplatin was AUC 16 (equivalent to a median of 1,189 mg/m(2)). The relationship of target AUC to measured AUC was linear (r(2) =. 29; P =.0011). The overall response rate was 96%, with a complete clinical response rate of 67%. The median time to progression from the first PBSC reinfusion was 49.5 weeks (range, 8 to 156+ weeks).
  
  
  CONCLUSIONS
  Multiple cycles of high-dose carboplatin (AUC 16) and paclitaxel (250 mg/m(2)) can be safely administered with GM-CSF and PBSC support. Although this regimen is safe, feasible, and active, the use of multiple cycles of high-dose chemotherapy as front-line treatment remains experimental and should only be used in the context of a clinical trial.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111, USA. rj_schilder@fccc.edu
authors.forename: R J
authors.initials: RJ
authors.lastname: Schilder
authors.forename: S
authors.initials: S
authors.lastname: Johnson
authors.forename: J
authors.initials: J
authors.lastname: Gallo
authors.forename: S
authors.initials: S
authors.lastname: Kindsfather
authors.forename: B
authors.initials: B
authors.lastname: Rogers
authors.forename: M A
authors.initials: MA
authors.lastname: Bookman
authors.forename: M M
authors.initials: MM
authors.lastname: Millenson
authors.forename: M
authors.initials: M
authors.lastname: Boente
authors.forename: N
authors.initials: N
authors.lastname: Rosenblum
authors.forename: S
authors.initials: S
authors.lastname: Litwin
authors.forename: R F
authors.initials: RF
authors.lastname: Ozols
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000494:pharmacology; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D003131:Combined Modality Therapy / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D016190:Carboplatin; D017239:Paclitaxel