Phase II trial of a simultaneous radiochemotherapy with cisplatinum and paclitaxel in combination with hyperfractionated-accelerated radiotherapy in locally advanced head and neck tumors.

BACKGROUND: Simultaneous radiochemotherapy (RCT) is the treatment of choice for locally advanced head and neck cancers. In order to evaluate the toxicity and the survival rates, we investigated the use of a very aggressive combination protocol that included cisplatinum and paclitaxel combined with hyperfractionated-accelerated radiotherapy. The final results of the phase II study are listed below.
METHODS: For the phase II trial 32 patients (29 male, 3 female) with histologically diagnosed locally advanced non-metastatic squamous cell carcinoma of the head and neck in stage III/IV were treated from 1999 to 2003. Radiotherapy was administered as hyperfractionated-accelerated to a total dose of 70.6 Gy. The chemotherapy regime included administering cisplatinum on d 1-5 and on d 29-33 at doses of 20 mg/m(2) and during the entire course of treatment paclitaxel was administered twice a week at doses of 25 mg/m(2).
RESULTS: The 5-yr overall and disease-free survival rates were 48% and 43%. Twenty-two (69%) patients reached a clinically complete response and 8 (25%) a partial response (for two of the patients the response rate is not known). Two (6%) patients died during the treatment. Seven (22%) patients developed local recurrences and six of these patients have in the meantime died. With regards to the four (12%) patients who developed distant metastases, three of them have in the meantime died and two (6%) patients have died as a result of secondary malignancies. Seven out of 25 (28%) patients developed grade 3 erythema and 22 out of 31 (71%) patients developed grade 3 mucositis. No cases of grade 4 mucositis were observed; however, one patient out of 25 (4%) was classified with grade 4 dermatitis. One out of 24 (4%) patients developed grade 2 liver toxicity and 1 out of 22 patients (5%) developed grade 3 thrombopenia. Seven out of 25 patients (28%) developed a grade 3 leukopenia, and 2 out of 25 patients (8%) experienced a grade 4 eutropenic infection. Dysphagia was a significant late toxicity. Out of 24 patients, 4 (17%) developed a grade 3 dysphagia and 1 (4%) patient developed a grade 3 xerostomia. An osteoradionecrosis was seen in 2 out of 24 (8%) patients.
CONCLUSION: This very aggressive radiochemotherapy protocol yielded excellent response and overall survival rates; however it is associated with a very high rate of acute toxicity. Therefore, in such cases where acute toxicity resulted, extensive supportive care is required.