Phase II Trial of 5-Fluorouracil and High-Dose Leucovorin in Recurrent Adenocarcinoma of the Cervix: A Gynecologic Oncology Group Study

• Published in: Gynecologic oncology 1997-12, Vol.67 (3), p.255-258
• Main Authors: Look, Katherine Y., Blessing, John A., Valea, Fidel A., McGehee, Ramon, Manetta, Alberto, Webster, Kenneth D., Andersen, Willie A.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adult; Aged; Antimetabolites, Antineoplastic - administration & dosage; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Chemotherapy; Drug Administration Schedule; Female; Fluorouracil - administration & dosage; Humans; Leucovorin - administration & dosage; Medical sciences; Middle Aged; Neoplasm Recurrence, Local; Pharmacology. Drug treatments; Treatment Outcome; Uterine Cervical Neoplasms - drug therapy
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1006/gyno.1997.4886

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/m 2of intravenous (iv) leucovorin with 370 mg/m 2of iv 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 ≤ 1.5× normal and SGOT and alkaline phosphatase ≤ 3× normal, serum creatinine ≤ 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. Conclusion.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.