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. This 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 eligible 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 and confirmed negative para-aortic lymph nodes. Eligibility was limited to clinical stage IIB through IVA. HDXR was given orally, twice weekly at a dose of 2.5 g/m2; C on Days 1 and 29 at 50 mg/m2; and 5-FU by 96-hr infusion on Days 2-5 and 30-33 at a starting dose of 800 mg/m2.

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 27 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 second course. Clinical response was excellent with complete and partial response rate of 93.3%. Median time to progression has not been reached.

CONCLUSION: Although this dose and schedule could be successfully administered, the delays in therapy should be avoided by a lower starting dose of hydroxyurea. Stomatitis was not a dose-limiting toxicity. These results have formed the basis of a phase III trial comparing this regimen to two other chemoradiation regimens.