title: Topotecan in combination with cisplatin for the treatment of stage IVB, recurrent, or persistent cervical cancer.
abstract: OBJECTIVE
  Topotecan, a camptothecin analog previously approved for the treatment of ovarian cancer and small-cell lung cancer, was granted regular approval by the US Food and Drug Administration (FDA) on June 14, 2006, for use in combination with cisplatin to treat women with stage IVB, recurrent, or persistent carcinoma of the cervix not amenable to curative treatment with surgery and/or radiation therapy. The purpose of this summary is to review the database supporting this approval.
  
  
  METHODS
  In a randomized multicenter study enrolling 293 eligible patients, topotecan plus cisplatin (TC) was compared with cisplatin monotherapy. The TC regimen consisted of cisplatin 50 mg/m2 IV over 1 hour on day 1 and topotecan 0.75 mg/m2 IV over 30 minutes on days 1, 2, and 3 every 21 days.
  
  
  RESULTS
  There was a clinically relevant and statistically significant improvement in overall survival in the TC treatment arm. Median overall survival was 9.4 months (95% confidence interval [CI]:7.9-11.9) in the TC arm, compared to 6.5 months (95% CI:5.8-8.8) with cisplatin alone. The unadjusted hazard ratio for overall survival between treatment arms was 0.76 (95% CI: 0.59-0.98, P = .033) favoring the combination arm. The most common toxicities with TC included myelosuppression, nausea and vomiting, mucositis, rash, and hepatotoxicity.
  
  
  CONCLUSIONS
  This report describes the FDA's review supporting this first approval of a chemotherapeutic drug for advanced cervical cancer based on demonstration of a survival benefit.
authors.affiliation: Office of Oncology Drug Products, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland 20993, USA. michael.brave@fda.hhs.gov
authors.forename: Michael
authors.initials: M
authors.lastname: Brave
authors.forename: Ramzi
authors.initials: R
authors.lastname: Dagher
authors.forename: Ann
authors.initials: A
authors.lastname: Farrell
authors.forename: Sophia
authors.initials: S
authors.lastname: Abraham
authors.forename: Roshni
authors.initials: R
authors.lastname: Ramchandani
authors.forename: Jogarao
authors.initials: J
authors.lastname: Gobburu
authors.forename: Brian
authors.initials: B
authors.lastname: Booth
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Jiang
authors.forename: Rajeshwari
authors.initials: R
authors.lastname: Sridhara
authors.forename: Robert
authors.initials: R
authors.lastname: Justice
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D015996:Survival Rate; D019772:Topotecan / Q000008:administration & dosage; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D019772:Topotecan; D002945:Cisplatin