LONIDAMINE PLUS CYCLOPHOSPHAMIDE IN THE TREATMENT OF ADVANCED NONSMALL CELL LUNG-CANCER IN THE ELDERLY - A PHASE-II STUDY

Aim and background: The aim of this Phase II trial was to verify the t herapeutic activity and tolerability of chemotherapy with lonidamine ( LND) plus cyclophosphamide (CTX) in advanced non-small cell lung cance r (NSCLC) in the elderly. The rationale of the combination is reported . CTX showed mild toxicity, with a 12% objective response (OR) in mono chemotherapy; LND potentiated the in vitro antiproliferative activity of alkylating agents, mainly CTX, without increasing myelotoxicity, pa rticularly important in the elderly. Methods: The schedule consisted o f CTX, 600 mg/m(2)/i.v. on day 1 every 21 days for 6 cycles; LND, 450 mg/die/p.o. from day 1 to progression. Results: Between November 1990 and April 1991, 41 patients with stage III-IV NSCLC were enrolled; 35 were assessable for response, Median age was 73 years (range, 71-79 ye ars); 13 patients (32%) presented stage III A, 20 (49%) stage III b, a nd 8 (19%) stage IV disease. Cardiovascular conditions and/or chronic respiratory failure contraindicated surgical treatment in stage III A patients. Of enrolled patients, 14.6% experienced PR, 48.8% SD and 14. 6% dropped out of the study. Median time to progression was 4 months ( range, 2-9 months) and median survival 9 months (range 3-45 months). N o patient showed WHO grade IV LND-related toxicity. In 1 patient (2.5% ), LND was discontinued after 5 therapy cycles due to WHO grade III my algia; in 80% of patients, LND oral dosage was reduced to 300 mg/day d ue to WHO grade II myalgia, and 20% of patients completed treatment wi th the full dose. Conclusions: CTX plus LND can be considered a well t olerated therapeutic approach in the elderly with NSCLC with good PS a nd good liver, renal and cardiac conditions, but 14.6% PR is a slightl y better result as compared with 12% PR obtainable with CTX alone as r eported in the literature, even though most patients presented with ad vanced disease and no specific toxic effect was observed. Therefore, a confirmatory randomized trial (CTX vs CTS plus LND) would hardly be u seful.