Phase II trial of methylglyoxal bis-guanylhydrazone (MGBG) in refractory small cell lung cancer

Abstract

Methylglyoxal bis-guanylhydrazone (MGBG), a potent inhibitor of polyamine synthesis, has demonstrated single agent activity against a number of tumor types including malignant lymphomas and head and neck, esophageal and non-small cell lung cancers. The growth of small cell lung cancer (SCLC) cell lines can be arrested by polyamine inhibition. Therefore a phase II trial was conducted in twenty-four patients with refractory SCLC. MGBG was administered by intravenous infusion at a dose of 500 mg/m2 per week for four cycles and then every two weeks thereafter. The dose was escalated by 100 mg/m2 every two weeks in the absence of toxicity greater than or equal to grade 2. One patient achieved a partial response of objectively measurable lung disease and supraclavicular adenopathy. Three patients had stable disease. Dose limiting toxicity consisted primarily of mild to moderate nausea, vomiting, stomatitis and/or diarrhea. Myelosuppression was uncommon and rarely dose limiting. We conclude that MGBG in the dose and schedule used does not have significant activity as a single agent in previously treated small cell lung cancer.