Hyperfractionated radiation therapy plus chemotherapy in locally advanced cervical cancer: Results of two phase I dose-escalation gynecologic oncology group trials

Objective. The aims of this study were to assess the early and late toxicit ies of multiple-daily-fraction whole pelvic radiation plus concurrent chemo therapy with either hydroxyurea or 5-fluorouracil (5-FU)/cisplatin and to d etermine the maximum tolerated external radiation dose in conjunction with brachytherapy, when given with either of these drug regimens, as treatment for locally advanced carcinoma of the cervix. Methods. The first study (GOG 8801) of 38 patients utilized hydroxyurea as a single oral dose of 80 mg/kg to a maximum of 6 g at least 2 h prior to a radiation treatment twice every week. In the second study (GOG 8901) of 30 patients, cisplatin and 5-FU were used concomitantly with radiotherapy. Fif ty milligrams per square meter of cisplatin was administered on days 1 and 17 of external radiation. 5-FU was given by continuous intravenous infusion at a dose of 1000 mg/m(2)/day for 4 consecutive days on days 2, 3, 4, 5, a nd 18, 19, 20, and 21 of external radiation therapy. Both studies utilized external radiation given by an accelerated hyperfractionated regimen of 1.2 Gy per fraction, two fractions per day. All patients were treated 5 days p er week with a minimum of 4 h between fractions. Results, Acute toxicity was manageable on both protocols but nausea, vomiti ng, and myelosuppression were more severe with hydroxyurea, Chronic toxicit y was primarily enteric and appeared to be dose-related. There was no obvio us correlation seen between pelvic failure rates and the radiation dose or between the chemotherapy regimens used. Conclusions. The defined maximal tolerated dose of whole pelvic radiation w as 57.6 Gy in 48 fractions which could be delivered in a hyperfractionated setting with concomitant chemotherapy, followed by brachytherapy, Follow-up is now sufficient that further adverse events should be rare. (C) 1999 Aca demic Press.