title: Phase II trial of topotecan and cisplatin in persistent or recurrent squamous and nonsquamous carcinomas of the cervix.
abstract: OBJECTIVE
  Cisplatin is a standard treatment in advanced, recurrent cervical cancer. Because topotecan is an established treatment in gynecologic malignancies such as ovarian cancer and exhibits nonoverlapping toxicity with cisplatin, a phase II trial was conducted to evaluate the tolerability and antitumor activity of a cisplatin/topotecan doublet in persistent or recurrent cervical cancer patients.
  
  
  METHODS
  Patients with bidimensionally measurable persistent or recurrent squamous cell and non squamous cell cervical cancer and adequate bone marrow were enrolled. Patients received 50 mg/m(2) of cisplatin intravenously over 1 h on Day 1 and 0.75 mg/m(2) of topotecan intravenously over 30 min on Days 1, 2, and 3 of 21-day cycles for six cycles or until disease progression. Tumor response and regimen toxicity were assessed using established Gynecologic Oncology Group criteria.
  
  
  RESULTS
  Thirty-two of 35 enrolled patients were evaluable for toxicity and tumor response. All but 2 evaluable patients had received previous radiotherapy. No patient received prior chemotherapy. The cisplatin/topotecan doublet was well tolerated, with 77 and 78% of courses given without interruption or delay and at full doses, respectively. As anticipated, the most common toxicity was hematologic, with grade 3/4 neutropenia and thrombocytopenia reported in 30 and 10% of cycles, respectively. The overall response rate was 28% (9/32), with 3 complete and 6 partial responses. The antitumor response in nonirradiated fields (30%) was similar to the response observed in previously irradiated fields (33%), suggesting good drug penetration. Median duration of response was 5 months (range, 2 to 15+ months). An additional 9 (28%) patients achieved stable disease. Median survival was 10 months, with 3 patients in lasting remission.
  
  
  CONCLUSIONS
  These results demonstrate that the cisplatin/topotecan combination is safe, well tolerated, and active in persistent or recurrent cervical cancer patients. A phase III, multicenter trial is under way (cisplatin/topotecan versus cisplatin) based on these favorable results to confirm the safety and efficacy profile in this patient population.
authors.affiliation: H. Lee Moffitt Cancer Center, Tampa, Florida 33612-9497, USA. Fiorica@moffitt.usf.edu
authors.forename: J
authors.initials: J
authors.lastname: Fiorica
authors.forename: R
authors.initials: R
authors.lastname: Holloway
authors.forename: B
authors.initials: B
authors.lastname: Ndubisi
authors.forename: J
authors.initials: J
authors.lastname: Orr
authors.forename: E
authors.initials: E
authors.lastname: Grendys
authors.forename: R
authors.initials: R
authors.lastname: Boothby
authors.forename: S
authors.initials: S
authors.lastname: DeCesare
authors.forename: J
authors.initials: J
authors.lastname: LaPolla
authors.forename: M
authors.initials: M
authors.lastname: Hoffman
authors.forename: J
authors.initials: J
authors.lastname: Patel
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
chemical_list: D019772:Topotecan; D002945:Cisplatin