title: Topotecan is an active agent in the first-line treatment of metastatic or recurrent endometrial carcinoma: Eastern Cooperative Oncology Group Study E3E93.
abstract: OBJECTIVE
  To determine the clinical activity and the toxicity profile of the topoisomerase-I inhibitor, topotecan, in women with recurrent or advanced endometrial carcinoma.
  
  
  METHODS
  A prospective, phase II clinical trial was initiated by the Eastern Cooperative Oncology Group (ECOG). Patients had histologically confirmed advanced or recurrent endometrial carcinoma, measurable disease, no prior cytotoxic therapy, an ECOG performance status of 0 to 2, and evidence of disease progression while on progestins or after radiation therapy. Topotecan was administered at 1.5 mg/m(2) (or 1.2 mg/m(2) for patients with prior pelvic radiation) intravenously daily for 5 days every 3 weeks.
  
  
  RESULTS
  A total of 44 patients were enrolled; 42 were eligible. The study was suspended because of unexpected toxicities, primarily sepsis and bleeding. After toxicity review, the study was reopened using lower doses of topotecan (1.0 mg/m(2) or 0.8 mg/m(2) for patients with prior radiation therapy). In addition, prophylactic use of growth factors was allowed after the first cycle, and patients with performance status of 2 were excluded. The major toxicities were hematologic and gastrointestinal. Among the 40 assessable patients, there were three (7.5%) complete responders and five partial responders (12.5%), for an overall response rate of 20%. The median duration of response was 8.0 months and of overall survival was 6.5 months.
  
  
  CONCLUSIONS
  Topotecan is an active agent for the treatment of advanced endometrial carcinoma. At the doses and schedules initially used, toxicities were unacceptable; however, at the modified doses, toxicities were acceptable and clinical activity was preserved.
authors.affiliation: Department of Oncology, Division of Hematology-Oncology, Weill Medical College of Cornell University, 525 E 68th St, STARR 353, New York, NY 10021, USA. scw2004@med.cornell.edu
authors.forename: Scott
authors.initials: S
authors.lastname: Wadler
authors.forename: Donna E
authors.initials: DE
authors.lastname: Levy
authors.forename: Sarah T
authors.initials: ST
authors.lastname: Lincoln
authors.forename: Gamini S
authors.initials: GS
authors.lastname: Soori
authors.forename: Julian C
authors.initials: JC
authors.lastname: Schink
authors.forename: Gary
authors.initials: G
authors.lastname: Goldberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011446:Prospective Studies; D015996:Survival Rate; D019772:Topotecan / Q000009:adverse effects / Q000627:therapeutic use*; D014481:United States / Q000453:epidemiology
chemical_list: D000970:Antineoplastic Agents; D019772:Topotecan