title: Phase II study of intravenous topotecan as a 5-day infusion for refractory epithelial ovarian carcinoma.
abstract: OBJECTIVE
  To determine the efficacy and toxicity of topotecan administered as a 5-day intravenous infusion in patients with advanced ovarian cancer refractory to cisplatin-based chemotherapy.
  
  
  METHODS
  Thirty patients with advanced epithelial ovarian cancer refractory to cisplatin-based chemotherapy received intravenous infusions of topotecan 1.5 mg/m2 delivered over 30 minutes each day for 5 days. A course was repeated every 21 days. The patient eligibility requirements included age > or = 18 years, Zubrod score < or = 2, measurable disease, adequate hepatic and renal function, neutrophil count > or = 1,500/microL, platelet count > or = 100,000/microL, and anticipated survival > or = 3 months.
  
  
  RESULTS
  Twenty eight patients were assessable for response and toxicity. All patients were assessable for survival. The major toxicity from administration of topotecan at this dose schedule was myelosuppression; 21 patients required dose reductions. Four patients had neutropenic fever that required hospitalization, and seven patients required platelet transfusions. Maculopapular pruritic exanthema occurred in 20% of patients; gastrointestinal side effects were mild. No deaths were reported on the study. At dose levels of 1.5, 1.25, and 1.0 mg/m2, 61%, 31%, and 25% of patients, respectively, required dose reductions. Of 28 assessable patients, four (14%; 95% confidence interval [CI], 4% to 34%) achieved a partial response (PR) at a median of 1.4 months and lasting 8.9 months, and 17 had stable disease (SD). The overall median survival time was 10.0 months (95% CI, 8.1 to 13.5).
  
  
  CONCLUSIONS
  Topotecan shows modest clinical activity against cisplatin-refractory ovarian cancer, although the dose-intensity is compromised by the depth of the granulocyte nadir and the duration of granulocytopenia. Further studies of topotecan may necessitate a reevaluation of optimal dose schedule, with the possible incorporation of multilineage cytokines, and its activity in taxane-resistant tumors.
authors.affiliation: University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Kudelka
authors.forename: D
authors.initials: D
authors.lastname: Tresukosol
authors.forename: C L
authors.initials: CL
authors.lastname: Edwards
authors.forename: R S
authors.initials: RS
authors.lastname: Freedman
authors.forename: C
authors.initials: C
authors.lastname: Levenback
authors.forename: P
authors.initials: P
authors.lastname: Chantarawiroj
authors.forename: C
authors.initials: C
authors.lastname: Gonzalez de Leon
authors.forename: E E
authors.initials: EE
authors.lastname: Kim
authors.forename: T
authors.initials: T
authors.lastname: Madden
authors.forename: B
authors.initials: B
authors.lastname: Wallin
authors.forename: M
authors.initials: M
authors.lastname: Hord
authors.forename: C
authors.initials: C
authors.lastname: Verschraegen
authors.forename: M
authors.initials: M
authors.lastname: Raber
authors.forename: J J
authors.initials: JJ
authors.lastname: Kavanagh
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000627:therapeutic use; D019772:Topotecan
chemical_list: D000970:Antineoplastic Agents; D019772:Topotecan; D017239:Paclitaxel; D002945:Cisplatin; D002166:Camptothecin