mitoguazone and Carcinoma--Small-Cell

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.

Topics: Aged; Carcinoma, Small Cell; Drug Evaluation; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mitoguazone

Topics: Adult; Aged; Carcinoma, Small Cell; Drug Evaluation; Female; Guanidines; Humans; Lung Neoplasms; Male; Middle Aged; Mitoguazone; Recurrence

Fifty-two patients with metastatic or recurrent non-small-cell lung cancer (NSCLC) were treated, during a phase II trial, with methylglyoxal-bis-(guanylhydrazone) (MGBG). Of the 44 patients who had adequate trials, 4 had partial responses (PR), for an overall 9% PR rate. Response durations ranged from 3 to 5+ months. Prior treatment with chemotherapy may have adversely affected response rate; 15% of previously untreated patients responded, compared to only 4% of previously treated patients. A syndrome of weakness and fatigue was the most serious side effect. Anorexia and weight loss, stomatitis, nausea and vomiting, diarrhea, and peripheral neuropathy were the other toxic effects. We conclude that MGBG has activity in NSCLC, especially in previously untreated patients, and further studies are indicated in that population.

Topics: Adenocarcinoma; Anorexia; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Drug Evaluation; Fatigue; Female; Guanidines; Humans; Lung Neoplasms; Male; Mitoguazone