PHASE-II TRIAL OF 5-FLUOROURACIL AND HIGH-DOSE LEUCOVORIN IN RECURRENT ADENOCARCINOMA OF THE CERVIX - A GYNECOLOGIC-ONCOLOGY-GROUP STUDY

Objective. The objective of the study was to determine the response ra te and associated toxicity of 5-fluorouracil and high-dose leucovorin in patients with recurrent adenocarcinoma of the cervix. Methods. Betw een December 1993 and October 1995, 53 patients with recurrent adenoca rcinoma of the cervix were entered into a Phase II trial utilizing 200 mg/m(2) of intravenous (iv) leucovorin with 370 mg/m(2) of iv 5-fluor ouracil daily for 5 days every 4 weeks for two courses, then every 5 w eeks until disease progression, Eligibility criteria were a Gynecologi c Oncology Group (GOG) performance status of 0-2, adequate bone marrow reserve, adequate liver function with bilirubin less than or equal to 1.5 x normal and SGOT and alkaline phosphatase greater than or equal to 3 x normal, serum creatinine less than or equal to 2 mg%, and signe d informed consent. Standard GOG toxicity and response criteria were e mployed. Results. Six patients were ineligible because of wrong cell t ype (N = 3), insufficient pathology materials (N = 2), or a second pri mary (N = 1); therefore 45 were evaluable for toxicity. Two patients d id 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% (16/4 5) developed grade 4 neutropenia, Grade 3 or 4 thrombocytopenia was se en in 1 patient each (2.1%). Grade 3 gastrointestinal toxicity with na usea, vomiting, diarrhea, dehydration, or stomatitis was of grade 3 se verity in 11.1% (5/45) and grade 4 in 6.7% (3/45). There were four par tial responses and two complete responses for an overall response rate of 14%. The duration of the complete responses was 17.3 and 8.8+ mont hs, None of the patients with responses had previously received chemot herapy. Conclusion. The schedule of 5-fluorouracil and leucovorin exhi bits moderate activity in patients with previously treated adenocarcin oma of the cervix and should be considered for a trial in chemotherapy -naive patients. (C) 1997 Academic Press.