Lonidamine in head and neck cancer: an overview

Lonidamine (LNM) has been employed in the treatment of advanced head and neck cancer (H & N) primarily with radiotherapy. It has been proposed that LNM potentiates the effects of radiation by inhibiting repair of potentially lethal damage by interfering with the mitochondrial associated repair processes. In addition, LNM appears to be more effective with fractionated doses of radiotherapy, which in light of the current emphasis on hyper/accelerated fractionation schemes may make it more efficacious. Initial H & N studies comparing LNM treated patients to historical controls report a complete response (CR) rate of 65% versus 45% respectively. All major H & N sites were included. Subsequent nonrandomized Phase II studies, although containing small numbers of patients, showed LNM to be ineffective as a single agent in patients previously treated with chemotherapy and not significantly different when radiotherapy was given with conventional dose rates. In a randomized Phase III study in which patients received an accelerated radiotherapy schedule (150 cGy bid) with either lonidamine or placebo, the CR rate was not significantly different, however, the local regional control rate was 48% versus 25% in favor of the LNM group. In addition, the 3 and 5 year duration of resonse (44% and 42% versus 26% and 17%) was improved in the LNM group. However, the 3-year actuarial survival rate was not different (49% v 43%). In summary the role of LNM as a radiopotentiator in advanced head and neck cancer appears to improve the local control rate, although survival was not significantly changed. However, future studies employing hyperfractionation schemes may show that the improved local control rate will translate into improved survival.