Lonidamine plus cyclophosphamide in the treatment of adanced non-small cell lung cancer in the elderly: a phase II study.

AIM AND

BACKGROUND

The aim of this Phase II trial was to verify the therapeutic activity and tolerability of chemotherapy with lonidamine (LND) plus cyclophosphamide (CTX) in advanced non-small cell lung cancer (NSCLC) in the elderly. The rationale of the combination is reported. CTX showed mild toxicity, with a 12% objective response (OR) in monochemotherapy; LND potentiated the in vitro antiproliferative activity of alkylating agents, mainly CTX, without increasing myelotoxicity, particularly important in the elderly.

METHODS

The schedule consisted of CTX, 600 mg/m2/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 years); 13 patients (32%) presented stage III A, 20 (49%) stage III b, and 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). No 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 myalgia; in 80% of patients, LND oral dosage was reduced to 300 mg/day due to WHO grade II myalgia, and 20% of patients completed treatment with the full dose.

CONCLUSIONS

CTX plus LND can be considered a well tolerated therapeutic approach in the elderly with NSCLC with good PS and good liver, renal and cardiac conditions, but 14.6% PR is a slightly better result as compared with 12% PR obtainable with CTX alone as reported in the literature, even though most patients presented with advanced disease and no specific toxic effect was observed. Therefore, a confirmatory randomized trial (CTX vs CTS plus LND) would hardly be useful.