Pattern of Failure in Long-Term Survivors after Radio-Chemotherapy for Inoperable Head and Neck Cancer

Abstract

Background: After conventionally fractionated radical radiotherapy for advanced unresectable squamous cell carcinoma of the tongue, the floor of mouth and the supraglottic larynx, oro- and hypopharynx loco-regional tumor control rates rarely exceed 30%. Therefore, cytotoxic chemotherapy has been added in an attempt to improve loco-regional tumor control rates and reduce the incidence of distant spread and ultimately long-term survival. Still, in these patients comorbidity may often compromise possible improvements achieved by treatment intensification. Patients and Methods: In a prospective phase II study from 1984 to 1989, patients with loco-regionally advanced head and neck carcinoma were treated with 3 courses of simultaneous radio-chemotherapy. Radiotherapy was administered in two fractions per day 1.8 Gy each. During one course from day 3 to day 11 23.4 Gy were delivered in 13 fractions. Chemotherapy consisted of cis-Platin 60 mg/m2, leucovorin 50 mg/m2 intravenous bolus and 5-FU 350 mg/m2 intravenous bolus on day 2 and leucovorin 100 mg/m2/24-hour continuous infusion and 5-FU 350 mg/m2/24 h from day 2 to 5. Treatment was repeated on days 22 and 44, total radiation dose was 70.2 Gy. From day 12 to 21 and 34 to 43 treatment breaks were scheduled. Results: 105 patients are evaluable with a follow-up from 36 to 105 months in surviving patients. The crude overall survival rate at 5 years is 29% the probability of progression-free survival is 39% (Kaplan-Meier estimations). Loco-regional recurrences were observed in 52 patients after a median interval of 11 (2-81) months. 16 patients developed distant metastases after a median interval of 21 (6-81) months. Conclusions: Compared with data from the literature the pattern of relapse is very similar to that observed after radical radiotherapy alone. Median interval to distant spread appears to be prolonged by simultaneous chemotherapy but this may be due to prolonged follow up. Three-year figures of loco-regional control and survival are valid parameters to apreciate long-term data. Since nearly a third of patients are long-term survivors chronic toxicity deserves special attention in future trials.