DOUBLE-BLIND RANDOMIZED STUDY OF LONIDAMINE AND RADIOTHERAPY IN HEAD AND NECK-CANCER

Purpose: Preclinical studies showed lonidamine to potentiate the effec ts of x-irradiation by inhibiting the repair of potentially lethal dam age. This Phase III double blind, placebo-controlled study was perform ed to evaluate whether lonidamine can increase the tumor control of ra diotherapy in the treatment of advanced head and neck cancer without a ny synergistic toxic effects on the exposed normal tissues. Methods an d Materials: Ninety-seven patients with Stages II-IV squamous cell car cinoma of the head and neck were enrolled. Separate analyses were done on the 96 eligible patients and the 90 patients who completed the pre scribed treatment regimen. Patients received radiotherapy up to a plan ned total of 60-66 Gy, in 2 daily fractions of 1.5 Gy each and either lonidamine (450 mg p.o. in three divided daily doses) or placebo, give n continuously for 3 months or up to 1 month after the end of radiothe rapy. Results: The rate of tumor clearance was 66% (32/48) in the loni damine group and 65% (31/48) in the placebo group, while the subsequen t failure rate was 50% and 77%, respectively (p < 0.05). The 3 and 5 y ear locoregional control rates in the adequately treated patients achi eving complete tumor clearance were 66% and 63% for lonidamine vs. 41% and 37% for placebo. The disease-free survival in adequately treated patients was significantly better in the lonidamine group (p < 0.03), with 3 and 5 year rates of 44% and 40%, respectively, vs. 23% and 19% in the placebo group. The overall survival rate for all eligible patie nts at both 3 and 5 years was 44% in the lonidamine group and 44% and 31%, respectively, in the placebo group. Both acute and late radiation reactions were similar in the two groups. Myalgia and testicular pain were the most frequent side effects of lonidamine with an incidence o f 8.5% and 4.2%, respectively. Conclusion: The addition of lonidamine to hyperfractionated radiotherapy was correlated with a statistically and clinically significant proportion of long-term disease-free patien ts. The toxicity of radiotherapy was not aggravated by the drug and th e overall tolerance of the combined regimen was acceptable.