Dihydro-5-azacytidine in malignant mesothelioma. A phase II trial demonstrating activity accompanied by cardiac toxicity. Cancer and Leukemia Group B.

Abstract

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.

• Authors: N J Yogelzang, J E Herndon 2nd, C Cirrincione, D C Harmon, K H Antman, J M Corson, Y Suzuki, M L Citron, M R Green
• Journal: Cancer (Cancer) Vol. 79 Issue 11 Pg. 2237-42 (Jun 01 1997) ISSN: 0008-543X [Print] United States
• PMID: 9179072 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antimetabolites, Antineoplastic
• 5,6-dihydro-5-azacytidine
• Azacitidine

Topics

• Adult
• Aged
• Aged, 80 and over
• Antimetabolites, Antineoplastic (adverse effects, therapeutic use)
• Arrhythmias, Cardiac (chemically induced)
• Azacitidine (adverse effects, analogs & derivatives, therapeutic use)
• Chest Pain (chemically induced)
• Female
• Humans
• Male
• Mesothelioma (drug therapy, mortality)
• Middle Aged
• Pleural Neoplasms (drug therapy, mortality)