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 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.
Look
K Y
KY
Department of Obstetrics & Gynecology, Indiana University School of Medicine, Indianapolis 46202, USA.
Blessing
J A
JA
Valea
F A
FA
McGehee
R
R
Manetta
A
A
Webster
K D
KD
Andersen
W A
WA
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*
D000964:Antimetabolites, Antineoplastic; D002955:Leucovorin; D005472:Fluorouracil