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Medline ® Abstract for Reference 201

of 'Overview of neurologic complications of non-platinum cancer chemotherapy'

Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-cell malignancies: a report from the Children's Oncology Group.
Berg SL, Blaney SM, Devidas M, Lampkin TA, Murgo A, Bernstein M, Billett A, Kurtzberg J, Reaman G, Gaynon P, Whitlock J, Krailo M, Harris MB, Children's Oncology Group
J Clin Oncol. 2005;23(15):3376.
PURPOSE: Nelarabine (compound 506U78), a water soluble prodrug of 9-b-d-arabinofuranosylguanine, is converted to ara-GTP in T lymphoblasts. We sought to define the response rate of nelarabine in children and young adults with refractory or recurrent T-cell disease.
PATIENTS AND METHODS: We performed a phase II study with patients stratified as follows: stratum 1:>or = 25% bone marrow blasts in first relapse; stratum 2:>or = 25% bone marrow blasts in>or = second relapse; stratum 3: positive CSF; stratum 4: extramedullary (non-CNS) relapse. The initial nelarabine dose was 1.2 g/m2 daily for 5 consecutive days every 3 weeks. There were two dose de-escalations due to neurotoxicity on this or other studies. The final dose was 650 mg/m2/d for strata 1 and two patients and 400 mg/m2/d for strata 3 and four patients.
RESULTS: We enrolled 121 patients (106 assessable for response) at the final dose levels. Complete plus partial response rates at the final dose levels were: 55% in stratum 1; 27% in stratum 2; 33% in stratum 3; and 14% in stratum 4. There were 31 episodes of>or = grade 3 neurologic adverse events in 27 patients (18% of patients).
CONCLUSION: Nelarabine is active as a single agent in recurrent T-cell leukemia, with a response rate more than 50% in first bone marrow relapse. The most significant adverse events associated with nelarabine administration are neurologic. Further studies are planned to determine whether the addition of nelarabine to front-line therapy for T-cell leukemia in children will improve survival.
Texas Children's Cancer Center, Baylor College of Medicine, 6621 Fannin St, MC3-3320, Houston, TX 77030, USA. sberg@txccc.org