Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea asan adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: A Gynecologic Oncology Group and Southwest Oncology Group Study

Purpose: In 1986, a protocol comparing primary radiation therapy (RT) plus hydroxyurea (HU) to irradiation plus fluorouracil (5-FU) and cisplatin (CF) was activated by the Gynecologic Oncology Group (GOG) for the treatment of patients with locally advanced cervical carcinoma. The goals were to deter mine the superior chemoradiation regimen and to quantitate the relative tox icities. Methods: All patients had biopsy-proven invasive squamous cell carcinoma, a denocarcinoma, or adenosquamous carcinoma of the uterine cervix, Patients u nderwent standard clinical staging studies and their tumors were found to b e International federation of Gynaecology and Obstetrics stages IIB, ill, o r IVA. Negative cytologic washings and para-aortic lymph nodes were require d for entry. Patients were randomized to receive either standard whole pelv ic PT with concurrent 5-FU infusion and bolus CF or the same PT plus oral H U. Results: Of 388 randomized patients, 368 were eligible; 177 were randomized to CF and 191 to HU. Adverse effects were predominantly hematologic or gas trointestinal in both regimens. Severe or life-threatening leukopenia was m ore common in the HU group (24%) than in the CF group (4%). The difference in progression-free survival (PFS) was statistically significant in favor o f the CF group (P =.033). The sites of progression in the two treatment gro ups were not substantially different. Survival was significantly better for the patients randomized to CF (P =.018). Conclusion: This study demonstrates that for patients with locally advanced carcinoma of the cervix, the combination of 5-FU and CF with PT offers pat ients better PFS and overall survival than HU, and with manageable toxicity . J Clin Oncol 17:1339-1348. (C) 1999 by American Society of Clinical Oncol ogy.