HYDROXYUREA, 5-FLUOROURACIL INFUSION, AND CISPLATIN ADJUNCT TO RADIATION-THERAPY IN CERVICAL-CARCINOMA - A PHASE I-II TRIAL OF THE GYNECOLOGIC-ONCOLOGY-GROUP

Background. In a previous study, the Gynecologic Oncology Group (GOG) compared hydroxyurea (HDXR) and the combination of cisplatin (C) and 5 -fluorouracil (5-FU) infusion as potentiators of radiation therapy, Th is study was undertaken to determine whether these two regimens could be combined, concurrent with pelvic radiation therapy in patients with locally advanced cervical cancer. Methods. The GOG entered 75 eligibl e and evaluable patients on a Phase I-II evaluation of HDXR, C, and 5- FU as adjuncts to radiation therapy for locally advanced carcinoma of the cervix. All patients had histologically verified primary disease a nd confirmed negative para-aortic lymph nodes. Eligibility was limited to clinical stage IIB through IVA, HDXR was given orally, twice weekl y at a dose of 2.5 g/m(2); C on Days 1 and 29 at 50 mg/m(2); and 5-FU by 96-hr infusion on Days 2-5 and 30-33 at a starting dose of 800 mg/m (2). Results. Forty-eight (64%) patients had stage IIB disease, 25 (33 %) had stage IIIB, and 2 had stage IVA tumors. Primary tumors 4 cm or less in size were present in 15 patients, between 4 and 6 cm were in 2 7 patients, and larger than 6 cm were observed in 33 patients. Grade 3 /4 acute toxicity was experienced by 41 (54.7%) patients. These acute toxicities caused delays in prescribed radiation therapy of more than 1 week in 14 (18.9%) and low doses of drug in 16 (21.3%), and only 26 (34.7%) patients had the scheduled dose escalation of 5-FU on their se cond course. Clinical response was excellent with complete and partial response rate of 93.3%. Median time to progression has not been reach ed. Conclusion. Although this dose and schedule could be successfully administered, the delays in therapy should be avoided by a lower start ing dose of hydroxyurea. Stomatitis was not a dose-limiting toxicity. These results have formed the basis of a phase III trial comparing thi s regimen to two other chemoradiation regimens. (C) 1997 Academic Pres s.