title: Phase I study of YK-176 (2'-deoxycoformycin) in patients with adult T-cell leukemia-lymphoma. The DCF Study Group.
abstract: YK-176 is a newly isolated 2'-deoxycoformycin (DCF), a potent inhibitor of adenosine deaminase, produced by Aspergillus nidulans. In a cooperative phase I study, YK-176 was administered to 22 patients, comprising 18 with adult T-cell leukemia-lymphoma (ATL), two with cutaneous T-cell lymphoma (CTCL), one with lymphoblastic lymphoma of T-cell type and one with carcinoma of the uterine cervix. Doses of YK-176 ranged from 3.0 to 9.0 mg/m2 and were given intravenously for three consecutive days. General malaise, anorexia, nausea, vomiting and low grade fever were frequently encountered, but were transient and not dose-related. At all dose levels hematological toxicities were mild. Two of seven patients receiving 7.0 mg/m2 for three consecutive days developed hepatocellular enzyme elevations (grade 2) and one patient, proteinuria (grade 2). One of two patients given 9.0 mg/m2 for three consecutive days manifested a life-threatening (grade 4) disturbance of consciousness and dyspnea, presumably ascribable to the drug-related toxicity of YK-176. The results suggest that 7.0 mg/m2 i.v. for three consecutive days is the maximum acceptable dose of YK-176. Central nervous system, pulmonary and possibly renal toxicities appeared to be dose-limiting. Out of the 20 patients evaluable for therapeutic response, partial remissions were observed in four, three with ATL and one with CTCL, who received less than 7.0 mg/m2 for three consecutive days. We conclude that YK-176 is an active agent against ATL at doses that may not be associated with prohibitive toxicity. A starting dose of 5.0 mg/m2 for three consecutive days is recommended for further phase II studies on ATL.
authors.affiliation: Department of Medical Oncology, National Cancer Center Hospital, Tokyo.
authors.forename: K
authors.initials: K
authors.lastname: Tobinai
authors.forename: M
authors.initials: M
authors.lastname: Shimoyama
authors.forename: S
authors.initials: S
authors.lastname: Inoue
authors.forename: S
authors.initials: S
authors.lastname: Takayasu
authors.forename: C
authors.initials: C
authors.lastname: Mikuni
authors.forename: M
authors.initials: M
authors.lastname: Kozuru
authors.forename: S
authors.initials: S
authors.lastname: Oda
authors.forename: H
authors.initials: H
authors.lastname: Nakajima
mesh_terms: D000328:Adult; D000368:Aged; D001066:Appetite / Q000187:drug effects; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D015649:Pentostatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D014839:Vomiting / Q000139:chemically induced
chemical_list: D015649:Pentostatin