Lonidamine + Vindesine

The combination of lonidamine and vindesine has been studied as a treatment for non-small cell lung cancer (NSCLC), particularly in elderly patients. Lonidamine interferes with the energy metabolism of cancer cells by inhibiting aerobic glycolytic activity through its effect on mitochondrially-bound hexokinase (HK). Vindesine is a vinblastine derivative with antineoplastic activity. A Phase III randomized FONICAP trial evaluated the efficacy and treatment compliance of this combination in elderly patients (over 70 years) with advanced NSCLC. The trial results showed limited efficacy, with only 3 partial responses among 104 evaluable patients and an overall median survival of 170 days, with neither drug nor the combination showing significant impact on survival. Treatment compliance was poor, with 9.4% of patients refusing to continue. Toxicity was generally mild but included myalgia, fatigue, and testicular pain (from lonidamine) and leukopenia (from vindesine or the combination). Researchers concluded that the low response rate and survival, combined with poor treatment compliance, did not support the usefulness of these "gentle" chemotherapies in elderly NSCLC patients. Other studies also investigated lonidamine in combination with other chemotherapy regimens for NSCLC.