Phase I/II study of simultaneous carboplatin and radiotherapy in unresectable squamous cell carcinoma of the head and neck.

ABSTRACT

Escalating dose levels of carboplatin together with simultaneous accelerated radiation were administered to 36 previously untreated patients with unresectable carcinomas of the head and neck (two stage III and 34 stage IV disease). Twenty-three patients received a total radiation dose of 58.8 Gy with two daily fractions of 2.1 Gy on days 1 to 4 in weeks 1, 2, and 5 and on another 2 days in week 6. Simultaneous carboplatin was given intravenously in escalating dose levels 20 mg/m2 in three patients, 30 mg/m2 in five patients, 40 mg/m2 in five patients, 50 mg/m2 in six patients, and 60 mg/m2 in four patients. Another 13 patients were treated with an escalated radiation dose of 67.2 Gy, which led to 2 additional days of chemoradiotherapy in week 6. Six patients in this group received carboplatin 60 mg/m2/d, and seven received 50 mg/m2/d. All patients were evaluable for toxicity according to World Health Organization (WHO) criteria, and 35 of 36 patients were evaluable for response. Dose-limiting toxicity was myelosuppression, with WHO grades 3 and 4 leukopenia in five of six patients treated with carboplatin 60 mg/m2 and 67.2 Gy radiation. In patients treated with carboplatin 50 mg/m2 and 67.2 Gy radiation, no grade 4 myelosuppression developed and toxicity was generally tolerable. Independent of the carboplatin dose, grade 3 or 4 mucositis was seen in 12 patients. No other toxicities above grade 2 occurred. There were 19 complete responses (53%) and 16 partial responses (44%). Comparing these results with our earlier data with sequential chemoradiotherapy (carboplatin/5-fluorouracil followed by conventional radiotherapy) indicated that the higher tumor-clearing rate of simultaneous chemoradiotherapy produced significantly better rates of survival and disease-free response.