title: Phase I study of paclitaxel and topotecan in patients with advanced tumors: a cancer and leukemia group B study.
abstract: OBJECTIVE
  To define the dose-limiting toxicities (DLTs) and the recommended phase II doses of paclitaxel combined with topotecan, without and with filgrastim support.
  
  
  METHODS
  Patients with advanced solid tumors and a maximum of one prior chemotherapy regimen for metastatic disease were eligible if they had a performance status of 0 to 1 and normal renal, hepatic, and bone marrow function. Prior treatment with taxanes or comptothecin analogs, and prior pelvic irradiation were not allowed. Patients with a history of cardiac disease or on medications known to affect cardiac conduction were excluded. The dose of topotecan was fixed at 1.0 mg/m2/d for 5 days. The dose of paclitaxel was escalated until the maximum-tolerated dose (MTD), without and with filgrastim 5 micrograms/kg subcutaneously (SC) on days 6 to 14, was reached. Paclitaxel was administered over 3 hours on day 1 before topotecan. Treatment cycles were repeated every 21 days.
  
  
  RESULTS
  Of 46 patients entered, 45 were assessable for toxicity and 34 for response. The principal toxicity was neutropenia. Without filgrastim, the MTD of paclitaxel was 80 mg/m2 on day 1 in combination with topotecan 1.0 mg/m2/d for 5 days. With filgrastim, the dose of paclitaxel was escalated to 230 mg/m2 in combination with the same dose of topotecan. At this dose level, one patient had hematologic DLT and a second patient developed neuromuscular DLT. Three patients had a partial response (PR): one with head and neck cancer, a second with non-small-cell lung cancer, and the third with colon cancer.
  
  
  CONCLUSIONS
  We conclude that paclitaxel can be given at clinically relevant doses in combination with topotecan and filgrastim. The recommended dose for phase II studies is paclitaxel 230 mg/m2 on day 1 and topotecan 1.0 mg/m2/day for 5 days with filgrastim 5 micrograms/kg on days 6 to 14.
authors.affiliation: University of California at San Diego, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Lilenbaum
authors.forename: M J
authors.initials: MJ
authors.lastname: Ratain
authors.forename: A A
authors.initials: AA
authors.lastname: Miller
authors.forename: J B
authors.initials: JB
authors.lastname: Hargis
authors.forename: D R
authors.initials: DR
authors.lastname: Hollis
authors.forename: G L
authors.initials: GL
authors.lastname: Rosner
authors.forename: S M
authors.initials: SM
authors.lastname: O'Brien
authors.forename: L
authors.initials: L
authors.lastname: Brewster
authors.forename: M R
authors.initials: MR
authors.lastname: Green
authors.forename: R L
authors.initials: RL
authors.lastname: Schilsky
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced / Q000628:therapy; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011994:Recombinant Proteins / Q000627:therapeutic use; D012074:Remission Induction; D013921:Thrombocytopenia / Q000139:chemically induced; D019772:Topotecan; D014481:United States
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D019772:Topotecan; D017239:Paclitaxel; D000069585:Filgrastim; D002166:Camptothecin