Lack of efficacy of high-dose methotrexate by 30-hour infusion in patients with progressive small cell carcinoma of the lung

Seventeen patients with small cell carcinoma of the lung (SCCL) refractory to at least one combination chemotherapy regimen were treated with a high-dose methotrexate (HDMTX) program consisting of 1500 mg/m² of MTX by iv infusion at a constant rate over 30 hrs following a priming dose of 50 mg/m² of MTX iv. Administration of calcium leucovorin was begun at the end of the infusion. Treatment was repeated every 2 weeks. No complete or partial responses were observed, and the median time to tumor progression was 4 weeks. Hematologic toxicity was much more severe than anticipated, with five patients having thrombocytopenic bleeding requiring platelet transfusions. This HDMTX regimen was both ineffective and unexpectedly toxic in our heavily pretreated patients with SCCL. Literature review discloses little evidence that HDMTX programs have superior activity to standard doses of MTX in this disease.