Prolonged continuous infusion of carboplatin and concomitant radiotherapy in advanced head and neck cancer. A phase I study.

A Phase I study on conventional radiotherapy and concomitant infusional chemotherapy with carboplatin (CBDCA) was initiated in order to evaluate the toxicity and feasibility of this combined treatment. Twenty-one patients with advanced head and neck carcinoma entered the study: 9 patients (Group A) received a 14-day infusion of 30 mg/m2 of CBDCA daily and 12 (Group B), a 21-day infusion beginning from the first day of radiotherapy. Total doses of 420 and 630 mg/m2 were given to group A and B, respectively. RT total dose ranged from 65 to 70 Gy with standard fractionation (180 cGy/5d/w). Major side effects observed were hematologic and mucosal. In group A grade 3 leukopenia was observed in five patients, grade 3 thrombocytopenia in one, and grade 3 mucositis in 2. In group B hematologic toxicity was severe: grade 3 and 4 leukopenia was seen in 4 and 3 patients, respectively; 3 patients had grade 3 and 2 patients grade 4 thrombocytopenia with a late appearance of nadir. Severe grade 3 mucositis was observed in 6 patients. Nineteen patients were evaluable for tumor response: 7/17 patients with stage III-IV disease achieved a CR and 8 a PR. According to our experience, prolonged infusion with CBDCA during conventional RT courses is feasible, though a certain level of toxicity remains. A 30 mg/m2 daily dose for 21-day infusion is associated with severe hematologic toxicity, while 14-day infusion can be considered the maximum tolerable dose. Whether CBDCA infusion has any advantage over bolus is yet to be confirmed.