title: A phase I/II study of topotecan in combination with carboplatin in recurrent epithelial ovarian cancer.
abstract: OBJECTIVE
  The purpose of this study was to define the maximum tolerated dose (MTD) of topotecan given as escalating doses combined to a fixed dosage of carboplatin in late relapsing ovarian carcinomas.
  
  
  METHODS
  Women with relapsing ovarian cancer more than 6 months after first-line treatment were eligible for the study. In the first phase of the trial, patients were allocated to escalating topotecan doses with a carboplatin fixed dose (AUC 5, according to Cockcroft's formula). If no "severe" adverse event occurred in 1 or more of the patients, the topotecan dose was increased. The starting dose of topotecan was 0.50 mg/m(2)/day, for 3 consecutive days, and the dose step was of 0.25 mg/m(2)/day, till 1.5 mg/m(2)/day. The study progressed then in a phase II trial.
  
  
  RESULTS
  A total of 39 patients entered the trial. Twenty took part in the escalating topotecan dose phase (4 per dose level, 0.50, 0.75, 1, 1.25, and 1.50 mg/m(2)/day) and 19 in the phase II. No severe adverse event was observed in the phase I of the trial, so the MTD was not reached. In the phase II trial topotecan was given to 1 mg/m(2)/day. Overall grade 3-4 neutropenia, lasting 7 days or less, was observed in 58.9% (23 patients). Thrombocytopenia occurred in 30.8% (12 patients) and grade 3 anemia in 25.6% (10 patients) of subjects. No life-threatening event occurred. Platelets or red blood cell transfusions were given in three cases (7.8%).
  
  
  CONCLUSIONS
  This daily-times-3-day schedule of topotecan in combination with carboplatin is safe.
authors.affiliation: Prima Clinica Ostetrico Ginecologica, Universita'di Milano, Via Commenda 12, Milan, 20142, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bolis
authors.forename: G
authors.initials: G
authors.lastname: Scarfone
authors.forename: C
authors.initials: C
authors.lastname: Sciatta
authors.forename: G P
authors.initials: GP
authors.lastname: Polverino
authors.forename: C
authors.initials: C
authors.lastname: Rosa
authors.forename: P
authors.initials: P
authors.lastname: Guarnerio
authors.forename: F
authors.initials: F
authors.lastname: Parazzini
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D019772:Topotecan; D016190:Carboplatin