A phase II study of VM-26 plus lonidamine in pretreated small cell lung cancer

SCLC relapsing or refractory after induction chemotherapy is a chemoresistant tumor. The outcome of salvage chemotherapy is poor, with low response rates (< 30%) and short survival times (3-4 months). The development of drug resistance is considered the major cause of failure of treatment. VM-26 is one of the most active drugs in SCLC. Lonidamine has shown to enhance in both vivo and vitro antitumor activity of several cytotoxic drugs acting on drug resistance mechanisms.

VM-26 and lonidamine were employed as salvage chemotherapy in 30 small cell lung cancer patients. The doses of chemotherapy used were: VM-26 100 mg/m2, i.v., days 1 to 3; lonidamine 600 mg, p.o., days 1 to 5, recycled every 3 weeks.

We observed 13.3% of objective response and a median survival of 4 months. All the responses were obtained in patients relapsing after a response to induction chemotherapy. Toxicity was moderate with no toxic death.

Our study shows that Lonidamine failed to increase the VM-26 activity in pretreated small cell lung cancer patients.