Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an 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 determine the superior chemoradiation regimen and to quantitate the relative toxicities. Methods: All patients had biopsy-proven invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, Patients underwent standard clinical staging studies and their tumors were found to be International federation of Gynaecology and Obstetrics stages IIB, ill, or IVA. Negative cytologic washings and para-aortic lymph nodes were required for entry. Patients were randomized to receive either standard whole pelvic PT with concurrent 5-FU infusion and bolus CF or the same PT plus oral HU. Results: Of 388 randomized patients, 368 were eligible; 177 were randomized to CF and 191 to HU. Adverse effects were predominantly hematologic or gastrointestinal in both regimens. Severe or life-threatening leukopenia was more common in the HU group (24%) than in the CF group (4%). The difference in progression-free survival (PFS) was statistically significant in favor of the CF group (P =.033). The sites of progression in the two treatment groups 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 patients better PFS and overall survival than HU, and with manageable toxicity. J Clin Oncol 17:1339-1348. (C) 1999 by American Society of Clinical Oncology.