title: Phase II study of cladribine (2-chlorodeoxyadenosine) in relapsed or refractory adult T-cell leukemia-lymphoma.
abstract: Adult T-cell leukemia-lymphoma (ATL) is a retrovirus-associated T-cell malignancy with an extremely poor prognosis; the median survival time of ATL patients with the acute or lymphoma type is less than 1 year with various combination chemotherapies. Cladribine (2-chlorodeoxyadenosine; 2-CdA), a purine analog resistant to degradation by adenosine deaminase, has shown definitive clinical activity against various lymphoid malignancies, including hairy cell leukemia, indolent lymphoma, and cutaneous T-cell lymphoma. An in vitro study showed the sensitivity of T-lymphoblastoid cell lines to cladribine, and a preceding Japanese phase I study of cladribine showed that 1 refractory patient with ATL achieved an objective response. To evaluate the therapeutic efficacy of cladribine in treating ATL, we conducted a multicenter phase II study. The plan was to administer cladribine to 30 ATL patients as 0.09 mg/kg per day by 7-day continuous intravenous infusion every 4 weeks for up to 3 courses. Before the planned interim analysis, 16 patients with relapsed or refractory ATL were enrolled, 15 of whom were eligible. Only 1 of the 15 eligible patients showed an objective response (overall response rate, 7%; 90% confidence interval, 0% to 28%), and 11 patients (73%) showed progressive disease, mostly during the first course of treatment. Because the upper limit of the 90% confidence interval of the overall response rate did not reach 30% in the interim analysis, the Independent Monitoring Committee advised us to discontinue patient enrollment. In conclusion, cladribine is not worthy of further investigation for the treatment of ATL.
authors.affiliation: Hematology Division, National Cancer Center Hospital, Tokyo, Japan. ktobinai@ncc.go.jp
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
authors.forename: Naokuni
authors.initials: N
authors.lastname: Uike
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Saburi
authors.forename: Takaaki
authors.initials: T
authors.lastname: Chou
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Etoh
authors.forename: Masato
authors.initials: M
authors.lastname: Masuda
authors.forename: Fumio
authors.initials: F
authors.lastname: Kawano
authors.forename: Masao
authors.initials: M
authors.lastname: Matsuoka
authors.forename: Hirokuni
authors.initials: H
authors.lastname: Taguchi
authors.forename: Torahiko
authors.initials: T
authors.lastname: Makino
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Asano
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tamura
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohashi
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000633:toxicity; D017338:Cladribine / Q000008:administration & dosage* / Q000633:toxicity; D018450:Disease Progression; D005260:Female; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D016879:Salvage Therapy / Q000379:methods*; D017211:Treatment Failure
chemical_list: D000970:Antineoplastic Agents; D017338:Cladribine