title: Phase I evaluation of docetaxel and topotecan for patients with advanced solid tumors.
abstract: BACKGROUND
  The authors administered a combination of docetaxel and topotecan with granulocyte-colony-stimulating factor (G-CSF) support in a Phase I study to define the maximum tolerated dose (MTD) of this regimen.
  
  
  METHODS
  Patients with advanced-stage solid tumors were eligible for this trial if they had a Zubrod performance status of </= 2 and normal renal, hepatic, and bone marrow function. No previous therapy with taxanes or topoisomerase inhibitors was allowed. The authors administered both docetaxel and topotecan in a dose-escalated manner until the MTD was reached. Docetaxel was given on Day 1 of each cycle before topotecan, which was administered intravenously on Days 1-3. Granulocyte-colony-stimulating factor (G-CSF) support with 5 microg/kg subcutaneous injections was initiated on Day 4 and continued until the absolute granulocyte count recovered to 2000/microL. Treatment cycles were repeated every 21 days.
  
  
  RESULTS
  Of the 11 patients enrolled in the current study, all were evaluable for toxicity and 10 were evaluable for response. A median of three treatment cycles was received (range, one to nine treatment cycles). The dose-limiting toxicity was Grade 4 (according to the National Cancer Institute Common Toxicity Criteria for Adverse Events [version 2.0]). neutropenia with fever. The MTD was 75 mg/m2 of docetaxel on Day 1 and 1.4 mg/m2 of topotecan on Days 1-3. There was one complete response and one partial response in patients with nasopharyngeal carcinoma and one partial response in a patient with small cell lung carcinoma (SCLC). The response durations were 24 weeks, 29 weeks, and >/= 244 weeks, respectively. At the time of last follow-up, both patients with nasopharyngeal carcinoma were still alive at 241 weeks and 244 weeks, respectively.
  
  
  CONCLUSIONS
  This trial demonstrated that a regimen of docetaxel and topotecan with G-CSF support was generally well tolerated and had promising activity in patients with nasopharyngeal and SCLC.
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Anne S
authors.initials: AS
authors.lastname: Tsao
authors.forename: Dong M
authors.initials: DM
authors.lastname: Shin
authors.forename: J Lynn
authors.initials: JL
authors.lastname: Palmer
authors.forename: Jin S
authors.initials: JS
authors.lastname: Lee
authors.forename: Bonnie S
authors.initials: BS
authors.lastname: Glisson
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D043823:Taxoids / Q000008:administration & dosage; D019772:Topotecan / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D019772:Topotecan