title: Phase II trial of 5-fluorouracil and high-dose leucovorin in recurrent adenocarcinoma of the cervix: a Gynecologic Oncology Group study.
abstract: OBJECTIVE
  The objective of the study was to determine the response rate and associated toxicity of 5-fluorouracil and high-dose leucovorin in patients with recurrent adenocarcinoma of the cervix.
  
  
  METHODS
  Between December 1993 and October 1995, 53 patients with recurrent adenocarcinoma of the cervix were entered into a Phase II trial utilizing 200 mg/m2 of intravenous (iv) leucovorin with 370 mg/m2 of i.v. 5-fluorouracil daily for 5 days every 4 weeks for two courses, then every 5 weeks until disease progression. Eligibility criteria were a Gynecologic Oncology Group (GOG) performance status of 0-2, adequate bone marrow reserve, adequate liver function with bilirubin < or = 1.5 x normal and SGOT and alkaline phosphatase < or = 3 x normal, serum creatinine < or = 2 mg%, and signed informed consent. Standard GOG toxicity and response criteria were employed.
  
  
  RESULTS
  Six patients were ineligible because of wrong cell type (N = 3), insufficient pathology materials (N = 2), or a second primary (N = 1); therefore 45 were evaluable for toxicity. Two patients did not have adequate response assessment; thus, 43 were evaluable for response. The median age was 50 (range, 28-79). Prior chemotherapy had been administered to 16 patients and radiotherapy to 40 patients. The median number of courses delivered was three (range, 1-22). The site of evaluable disease was pelvic in 25 patients and extra-pelvic in 18. Grade 3 neutropenia was seen in 17.8% (8/45) patients and 35.5% (16/45) developed grade 4 neutropenia. Grade 3 or 4 thrombocytopenia was seen in 1 patient each (2.1%). Grade 3 gastrointestinal toxicity with nausea, vomiting, diarrhea, dehydration, or stomatitis was of grade 3 severity in 11.1% (5/45) and grade 4 in 6.7% (3/45). There were four partial responses and two complete responses for an overall response rate of 14%. The duration of the complete responses was 17.3 and 8.8+ months. None of the patients with responses had previously received chemotherapy.
  
  
  CONCLUSIONS
  The schedule of 5-fluorouracil and leucovorin exhibits moderate activity in patients with previously treated adenocarcinoma of the cervix and should be considered for a trial in chemotherapy-naive patients.
authors.affiliation: Department of Obstetrics & Gynecology, Indiana University School of Medicine, Indianapolis 46202, USA.
authors.forename: K Y
authors.initials: KY
authors.lastname: Look
authors.forename: J A
authors.initials: JA
authors.lastname: Blessing
authors.forename: F A
authors.initials: FA
authors.lastname: Valea
authors.forename: R
authors.initials: R
authors.lastname: McGehee
authors.forename: A
authors.initials: A
authors.lastname: Manetta
authors.forename: K D
authors.initials: KD
authors.lastname: Webster
authors.forename: W A
authors.initials: WA
authors.lastname: Andersen
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
chemical_list: D000964:Antimetabolites, Antineoplastic; D002955:Leucovorin; D005472:Fluorouracil