title: Results of a phase II study of 506U78 in cutaneous T-cell lymphoma and peripheral T-cell lymphoma: CALGB 59901.
abstract: Nelarabine (compound 506U78), a novel purine nucleoside, is a soluble pro-drug of 9-beta-D-arabinofuranosylguanine (ara-G). Nelarabine is rapidly demethoxylated in blood by adenosine deaminase to ara-G. Pre-clinical and clinical studies have demonstrated the selective cytotoxicity of ara-G to T-lineage derived cells. CALGB Protocol 59901 was a Phase II study of nelarabine in patients with systemically untreated cutaneous T-cell lymphoma (CTCL) or refractory/relapsed systemic T-cell lymphoma (STCL). The objectives were to determine response rate, remission duration and safety profile associated with nelarabine given at 1.5 g m(-2) per day on days 1, 3 and 5 as an intravenous infusion every 21 days for a minimum of two cycles and to continue up to two cycles beyond CR up to a maximum of eight cycles. Nineteen patients were enrolled in the study: 11 CTCL and eight STCL patients. Grade 3 or 4 adverse events were documented in 50% and 28%, respectively. In particular, 33% of patients experienced Grade 3 or 4 neurologic toxicities. There were two partial remissions lasting 3 months and 5.5 months, respectively. Median event-free survival was 1.2 months and median overall survival was 3 months. Due to lack of efficacy and excessive toxicity, nelarabine is not recommended as monotherapy in adult patients with CTCL and STCL at this dose schedule.
authors.affiliation: Roswell Park Cancer Institute, Buffalo, NY 14263, USA. myron.czuczman@roswellpark.org
authors.forename: Myron S
authors.initials: MS
authors.lastname: Czuczman
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Porcu
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Johnson
authors.forename: Donna
authors.initials: D
authors.lastname: Niedzwiecki
authors.forename: Michael
authors.initials: M
authors.lastname: Kelly
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
authors.forename: James R
authors.initials: JR
authors.lastname: Cook
authors.forename: George
authors.initials: G
authors.lastname: Canellos
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Cheson
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001087:Arabinonucleosides / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000401:mortality; D016411:Lymphoma, T-Cell, Peripheral / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011355:Prodrugs / Q000009:adverse effects / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D011355:Prodrugs; C104457:nelarabine