title: 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.affiliation: Section of Hematolog/Oncology, University of Chicago Medical Center, Illinois 60637-1470, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Yogelzang
authors.forename: J E
authors.initials: JE
authors.lastname: Herndon
authors.forename: C
authors.initials: C
authors.lastname: Cirrincione
authors.forename: D C
authors.initials: DC
authors.lastname: Harmon
authors.forename: K H
authors.initials: KH
authors.lastname: Antman
authors.forename: J M
authors.initials: JM
authors.lastname: Corson
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: M L
authors.initials: ML
authors.lastname: Citron
authors.forename: M R
authors.initials: MR
authors.lastname: Green
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001374:Azacitidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002637:Chest Pain / Q000139:chemically induced; D005260:Female; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000401:mortality
chemical_list: D000964:Antimetabolites, Antineoplastic; C013938:5,6-dihydro-5-azacytidine; D001374:Azacitidine