title: A phase 2 study of oxaliplatin combined with continuous infusion topotecan for patients with previously treated ovarian cancer.
abstract: BACKGROUND
  Phase 2 trials suggest that prolonged intravenous (IV) infusion of the topoisomerase 1 inhibitor topotecan may be less toxic than when given by standard IV bolus 5-day administration. Oxaliplatin exhibits efficacy in platinum-pretreated disease and shows preclinical synergy with topoisomerase 1 inhibitors. We sought to determine the efficacy and safety of oxaliplatin plus infusion topotecan in recurrent platinum-pretreated ovarian cancer.
  
  
  METHODS
  Patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancers previously treated with 1 to 2 prior regimens including platinum and taxane received oxaliplatin (85 mg/m(2) day 1 and day 15) and topotecan (0.4 mg/m(2) per day) by continuous IV infusion over 14 days every 4 weeks. The primary objective of the trial was to estimate the objective response rate in platinum-resistant disease (stratum 1) and in platinum-sensitive disease (stratum 2). Toxicities were assessed in all patients.
  
  
  RESULTS
  Thirty-eight patients received 144 cycles of therapy (median, 4; range, 1-6). The most common grade 3 and grade 4 toxicities included thrombocytopenia (grade 3, 37%; and grade 4, 19%), neutropenia (grade 3, 37%; grade 4, 11%), and anemia (grade 3, 15%). Response occurred in 4 of 19 patients in stratum I (21%; 95% confidence intervals, 6%-46%) and 9 of 19 patients in stratum 2 (47%; 95% CI, 24%-71%). Three in each stratum had lengthy complete responses.
  
  
  CONCLUSIONS
  Biweekly oxaliplatin plus a 14-day continuous IV infusion of topotecan, given monthly, is an active regimen in platinum-pretreated ovarian cancer and merits additional evaluation.
authors.affiliation: *Division of Medical Oncology, Department of Medicine, Yale School of Medicine, New Haven, CT; †Division of Medical Oncology, Department of Medicine, and ‡Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY; §Beth Israel Cancer Center, Albert Einstein College of Medicine, NY; New York University School of Medicine, New York, NY, ∥Division of Biostatistics, Department of Population Health, New York University School of Medicine, New York, NY; ¶Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD; and #Department of Internal Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Stacey M
authors.initials: SM
authors.lastname: Stein
authors.forename: Amy
authors.initials: A
authors.lastname: Tiersten
authors.forename: Howard S
authors.initials: HS
authors.lastname: Hochster
authors.forename: Stephanie V
authors.initials: SV
authors.lastname: Blank
authors.forename: Bhavana
authors.initials: B
authors.lastname: Pothuri
authors.forename: John
authors.initials: J
authors.lastname: Curtin
authors.forename: Ilan
authors.initials: I
authors.lastname: Shapira
authors.forename: Benjamin
authors.initials: B
authors.lastname: Levinson
authors.forename: Percy
authors.initials: P
authors.lastname: Ivy
authors.forename: Benson
authors.initials: B
authors.lastname: Joseph
authors.forename: Achuta Kumar
authors.initials: AK
authors.lastname: Guddati
authors.forename: Franco
authors.initials: F
authors.lastname: Muggia
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000077216:Carcinoma, Ovarian Epithelial; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D007260:Infusion Pumps; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000401:mortality; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D000077150:Oxaliplatin; D016019:Survival Analysis; D019772:Topotecan / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D019772:Topotecan