Dihydro-5-azacytidine in malignant mesothelioma. A phase II trial demonstrating activity accompanied by cardiac toxicity. Cancer and Leukemia Group B.
(Clinical Trial;Journal Article;Multicenter Study)
BACKGROUND: Malignant mesothelioma is a disease that is refractory to chemotherapy. Therefore, the objective of this multi-institutional, cooperative group Phase II trial was to determine the efficacy of dihydro-5-azacytidine (DHAC), a pyrimidine analogue, in the treatment of malignant mesothelioma. METHODS: Forty-one patients with histologically confirmed malignant mesothelioma received 120-hour continuous infusions of DHAC (1,500 mg/m2/day every 21 days) until maximal response, intolerable toxicity, or disease progression. RESULTS: One patient had a complete response, two had objective partial responses, and four had regression of evaluable disease. The overall response rate was 17%. The one complete responder remains without disease progression at 6 years. Chest pain and nausea were the most common toxicities. Supraventricular tachycardia and pericardial effusion occurred in 20% and 15% of patients, respectively. In most patients, gastrointestinal effects were manageable. There was no significant hematologic toxicity. CONCLUSIONS: In malignant mesothelioma, a disease that is refractory to chemotherapy, dihydro-5-azacytidine has definite antitumor activity. Its modest hematologic toxicity profile favors its use in combination with other agents. Caution regarding cardiac arrhythmias and pericardial effusion is necessary.
Yogelzang, NJ; Herndon, JE; Cirrincione, C; Harmon, DC; Antman, KH; Corson, JM; Suzuki, Y; Citron, ML; Green, MR
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