High-dose methotrexate in small cell lung cancer. Lack of efficacy in preventing CNS relapse

Few studies have incorporated high-dose methotrexate (MTX) with leucovorin rescue in the treatment of small cell lung cancer (SCLC). Potentially therapeutic levels of MTX can be achieved in the central nervous system (CNS) by systemic administration of high doses of this drug. Utilizing a combination chemotherapy program of Adriamycin, vincristine, cyclophosphamide, and methotrexate, 31 patients were sequentially assigned to receive either low-dose MTX (40 mg/m2), or high-dose MTX (500 mg/m2) with leucovorin rescue. Radiation therapy to the primary site was also administered. At these dosage levels there were no statistically significant differences in response rate or survival between the two groups. High-dose MTX did not prevent the appearance of CNS disease; there being 2/15 and 3/15 CNS relapses in the HD MTX and LD MTX treated groups, respectively. The occurrence of CNS disease did not significantly affect overall survival as compared to patients not similarly affected.