title: Tolerance and activity of oxaliplatin with protracted topotecan infusion in patients with previously treated ovarian cancer. A phase I study.
abstract: BACKGROUND
  Topotecan 14-day infusion combined with cisplatin was highly active in ovarian cancer, but too myelosuppressive. We therefore sought to evaluate the feasibility of substituting oxaliplatin for cisplatin to improve safety.
  
  
  METHODS
  Ovarian and primary peritoneal cancer patients, pretreated with at least one prior platinum-containing regimen, performance status (PS) 0-1, without prior pelvic radiation were eligible. Topotecan was continuously infused days 1-15; oxaliplatin was given days 1 and 15; cycles were repeated every 28 days. Five dose levels were explored: topotecan (mg/m2/day)/oxaliplatin (mg/m2) doses: (1) 0.2/65; (2) 0.2/75; (3) 0.2/85; (4) 0.3/85; (5) 0.4/85.
  
  
  RESULTS
  Twenty-three patients (20 ovarian, 1 tubal, and 2 peritoneal) were entered: median age 56 years (range, 37-77); PS: 0=12 and 1=11; histology: papillary serous 7, serous 4, adenocarcinoma 8, poorly differentiated 2. Median of 4 cycles were delivered. Grade 3 neutropenia occurred in 3 of 7 patients at level 5 (with fever at levels 4 and 5), without grade 4 neutropenia or thrombocytopenia. Other toxicities were mild and reversible (mainly gastrointestinal), except one grade 3 neuropathy and one oxaliplatin-related grade 3 hypersensitivity reaction. Six objective responses (five of them complete) were documented among 22 patients spanning several dose levels.
  
  
  CONCLUSIONS
  Topotecan continuous infusion, combined with oxaliplatin, was associated with no grade 4 hematologic toxicity and evidence of activity. The recommended phase II dose is topotecan 0.4 mg/m2/day continuous infusion d1-15 with oxaliplatin 85 mg/m2 on days 1 and 15. A phase II evaluation as second-line treatment for both platinum-sensitive and -resistant ovarian cancer recurrences is ongoing.
authors.affiliation: Division of Medical Oncology, New York University School of Medicine, NYU Cancer Institute, NY 10016, USA. howard.hochster@med.nyu.edu
authors.forename: Howard
authors.initials: H
authors.lastname: Hochster
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Chen
authors.forename: Janice M
authors.initials: JM
authors.lastname: Lu
authors.forename: Day
authors.initials: D
authors.lastname: Hills
authors.forename: Joan
authors.initials: J
authors.lastname: Sorich
authors.forename: Juliet
authors.initials: J
authors.lastname: Escalon
authors.forename: Percy
authors.initials: P
authors.lastname: Ivy
authors.forename: Leonard
authors.initials: L
authors.lastname: Liebes
authors.forename: Franco
authors.initials: F
authors.lastname: Muggia
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000231:Adenocarcinoma, Papillary / Q000188:drug therapy / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077150:Oxaliplatin; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019772:Topotecan / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D019772:Topotecan