title: Prolonged topotecan infusion with cisplatin in the first-line treatment of ovarian cancer: an NYGOG and ECOG study.
abstract: OBJECTIVE
  To determine the toxicity and efficacy of combined therapy with cisplatin and prolonged infusion topotecan as front line therapy in women with epithelial ovarian cancer.
  
  
  METHODS
  Women with previously untreated, measurable and non-measurable epithelial ovarian cancer, stages Ic-IV were eligible. Patients were treated with cisplatin 75 mg/m(2) on day 1, followed by topotecan 0.3 to 0.4 mg/m(2)/day given as a continuous infusion over 14-21 days, every 28 days. Dose levels and duration of infusion were adjusted for toxicity as appropriate. Patients were evaluated for response to treatment and treatment toxicity by standard NYGOG criteria.
  
  
  RESULTS
  Sixty patients were enrolled. Among the 20 patients with post-surgical residual disease >2 cm, 80% [95% CI (56.3%, 94.3%)] demonstrated an objective response to therapy. The median progression-free survival for all 60 patients enrolled was 19.3 months with a median overall survival of 45.6 months given the median follow-up of 55 months (range 6-81 months). Five year survival is estimated to be 41%. Toxicity was observed in the first four patients treated with topotecan (0.4 mg/m(2)/day x 21 days) and dosing was continued at 0.3 mg/m(2)/day x 14 days thereafter. Of the 56 patients treated at the amended dose level, marrow suppression continued to be dose-limiting, with 86% of patients experiencing grade 3 or 4 neutropenia, 55% experiencing grade 3 or 4 thrombocytopenia and 50% of patients experiencing grade 3 or 4 anemia. Nonetheless, only 11/245 cycles administered were associated with febrile neutropenia and/or infection (8 port-related). Other non-hematologic toxicity was as expected. There were no treatment-related deaths.
  
  
  CONCLUSIONS
  This large, multicenter phase II study of prolonged infusion topotecan in combination with cisplatin demonstrated similar response, time to progression and survival compared with reported results of taxane and platinum combinations. Hematologic toxicity was greater but tolerated. Further studies investigating topotecan in combination with platinum therapy as a first line agent are warranted.
authors.affiliation: NYU School of Medicine and Cancer Institute, 160 East 34th Street, New York, NY 10016, USA. howard.hochster@med.nyu.edu
authors.forename: Howard S
authors.initials: HS
authors.lastname: Hochster
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Plimack
authors.forename: John
authors.initials: J
authors.lastname: Mandeli
authors.forename: Scott
authors.initials: S
authors.lastname: Wadler
authors.forename: Carolyn
authors.initials: C
authors.lastname: Runowicz
authors.forename: Gary
authors.initials: G
authors.lastname: Goldberg
authors.forename: James
authors.initials: J
authors.lastname: Speyer
authors.forename: Robert
authors.initials: R
authors.lastname: Wallach
authors.forename: Franco
authors.initials: F
authors.lastname: Muggia
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D019772:Topotecan; D002945:Cisplatin