Hyperfractionated radiation therapy and concurrent chemotherapy for advanced head and neck cancer

To investigate the feasibility of combining hyperfractionated radiotherapy regimen with concomitant chemotherapy and to assess its toxicity in patients with advanced head and neck carcinoma (HNC). Progression free survival (PFS) and overall survival (OS) were set as secondary end points.

Between November 2003 and November 2007, 48 patients with stage III and IV HNC who met the eligibility criteria were enrolled in the study. Hyperfractionated Radiation consisted of 120 Gys twice daily, 6 hours apart, for a total of 69.6 Gys in 58 fractions over 6 weeks and boost of 6 Gys in 3 fractions in case of residual disease. Three cycles of concurrent chemotherapy in the form of Cisplatin 75 mg/ m² on day 1 and Fluorouracil 750 mg/m² 24 hour infusion on day 1-4 during weeks 1, 4 and 6 of irradiation.

48 patients have completed the treatment to date. The median radiation dose was 72 Gys including the boost to residual lymph node or primary site. The treatment was delivered in a median overall period of 54 days, with a recorded median delay of 7 days. Grade 4 skin toxicity was experienced by 4.1% of patients only. Therapy was well tolerated (grade 3 mucositis in 21%, grade 4 in 26%, grade 3 leukopenia in 10%). Weight loss of more than 10 kg was reported in 10 (16.7%) of the cases. The most common late toxicity was mild to moderate xerostomia which was encountered in 34 (70.8%) cases and improved thereafter. Hypothyroidism was encountered in 7 (14.6%) of the cases. Complete response (CR) was observed in 40 patients (83.3%). Partial response (PR) was achieved in the remaining 8 patients (16.7%). Disease relapse occurred in 9 patients (18.8%) after complete response and 2 patients developed progressive disease after partial response. 3 patients relapsed locally, 5 patients developed distant metastasis and 1 patient developed both local and distant metastasis. 2 patients (4.1%) died of treatment complications, 8 patients (16.7%) died with progressive locoregional, and metastatic disease. The 2- year disease free survival was 77% and the 2- year overall survival was 79%.

Hyperfractionated radiotherapy and concurrent chemotherapy is tolerable. Results regarding LC and OS are encouraging as compared to conventional radiotherapy and concurrent chemotherapy.