Carboplatin plus radiation therapy in head and neck cancer

To determine toxicity and response, escalating dose levels of carboplatin were given simultaneously with accelerated radiation to 36 previously untreated patients with unresectable squamous cell carcinomas of the head and neck (SCCHN) (2 with stage III and 34 with 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 through 4 in weeks 1, 2, and 5 and on two additional days in week 6. Simultaneous carboplatin was given intravenously at escalating dose levels: 20 mg/m2 in 3 patients, 30 mg/m2 in 5 patients, 40 mg/m2 in 5 patients, 50 mg/m2 in 6 patients, and 60 mg/m2 in 4 patients. Another 13 patients were treated with an escalated radiation dose of 67.2 Gy, which resulted in 2 more days of radiochemotherapy in week 6. Six patients in this group received 60 mg/m2/d and 7 received 50 mg/m2/d carboplatin. 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 5 of 6 patients treated with 60 mg/m2 carboplatin and 67.2 Gy. With radiochemotherapy doses of 67.2 Gy and 50 mg/m2, no grade 4 myelosuppression occurred and toxicity was generally tolerable. Independent of the carboplatin dose, mucositis grade 3 or 4 was seen in 12 patients. No other toxicities above WHO grade 2 occurred, except in 2 patients with grade 3 nausea and vomiting. There were 19 complete responses (53%) and 16 partial responses (44%). Our preliminary data suggest that 50 mg/m2 carboplatin together with a total radiation dose of 67.2 Gy might be the best combination for advanced, unresectable SCCHN.