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Phase I study of 506U78 administered on a consecutive 5-day schedule in children and adults with refractory hematologic malignancies.

Publication ,  Journal Article
Kurtzberg, J; Ernst, TJ; Keating, MJ; Gandhi, V; Hodge, JP; Kisor, DF; Lager, JJ; Stephens, C; Levin, J; Krenitsky, T; Elion, G; Mitchell, BS
Published in: J Clin Oncol
May 20, 2005

PURPOSE: A phase I study was conducted to determine the maximum-tolerated dose (MTD), toxicity profile, and pharmacokinetics of a novel purine nucleoside, nelarabine, a soluble prodrug of 9-beta-D-arabinosylguanine (araG; Nelarabine), in pediatric and adult patients with refractory hematologic malignancies. PATIENTS AND METHODS: Between April 1994 and April 1997, 93 patients with refractory hematologic malignancies were treated with one to 16 cycles of study drug. Nelarabine was administered daily, as a 1-hour intravenous infusion for 5 consecutive days, every 21 to 28 days. First-cycle pharmacokinetic data, including plasma nelarabine and araG levels, were obtained on all patients treated. Intracellular phosphorylation of araG was studied in samples of leukemic blasts from selected patients. RESULTS: The MTDs were defined at 60 mg/kg/dose and 40 mg/kg/dose daily x 5 days in children and adults, respectively. Dose-limiting toxicity (DLT) was neurologic in both children and adults. Myelosuppression and other significant organ toxicities did not occur. Pharmacokinetic parameters were similar in children and adults. Accumulation of araGTP in leukemic blasts was correlated with cytotoxic activity. The overall response rate was 31%. Major responses were seen in patients with T-cell malignancies, with 54% of patients with T-lineage acute lymphoblastic leukemia achieving a complete or partial response after one to two courses of drug. CONCLUSION: Nelarabine is a novel nucleoside with significant cytotoxic activity against malignant T cells. DLT is neurologic. Phase II and III trials in patients with T-cell malignancies are encouraged.

Duke Scholars

Published In

J Clin Oncol

DOI

ISSN

0732-183X

Publication Date

May 20, 2005

Volume

23

Issue

15

Start / End Page

3396 / 3403

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Survival Rate
  • Risk Assessment
  • Recurrence
  • Oncology & Carcinogenesis
  • Neoplasm Staging
  • Neoplasm Invasiveness
  • Middle Aged
  • Maximum Tolerated Dose
  • Male
 

Citation

APA
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MLA
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Kurtzberg, J., Ernst, T. J., Keating, M. J., Gandhi, V., Hodge, J. P., Kisor, D. F., … Mitchell, B. S. (2005). Phase I study of 506U78 administered on a consecutive 5-day schedule in children and adults with refractory hematologic malignancies. J Clin Oncol, 23(15), 3396–3403. https://doi.org/10.1200/JCO.2005.03.199
Kurtzberg, J., T. J. Ernst, M. J. Keating, V. Gandhi, J. P. Hodge, D. F. Kisor, J. J. Lager, et al. “Phase I study of 506U78 administered on a consecutive 5-day schedule in children and adults with refractory hematologic malignancies.J Clin Oncol 23, no. 15 (May 20, 2005): 3396–3403. https://doi.org/10.1200/JCO.2005.03.199.
Kurtzberg J, Ernst TJ, Keating MJ, Gandhi V, Hodge JP, Kisor DF, et al. Phase I study of 506U78 administered on a consecutive 5-day schedule in children and adults with refractory hematologic malignancies. J Clin Oncol. 2005 May 20;23(15):3396–403.
Kurtzberg, J., et al. “Phase I study of 506U78 administered on a consecutive 5-day schedule in children and adults with refractory hematologic malignancies.J Clin Oncol, vol. 23, no. 15, May 2005, pp. 3396–403. Pubmed, doi:10.1200/JCO.2005.03.199.
Kurtzberg J, Ernst TJ, Keating MJ, Gandhi V, Hodge JP, Kisor DF, Lager JJ, Stephens C, Levin J, Krenitsky T, Elion G, Mitchell BS. Phase I study of 506U78 administered on a consecutive 5-day schedule in children and adults with refractory hematologic malignancies. J Clin Oncol. 2005 May 20;23(15):3396–3403.

Published In

J Clin Oncol

DOI

ISSN

0732-183X

Publication Date

May 20, 2005

Volume

23

Issue

15

Start / End Page

3396 / 3403

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Survival Rate
  • Risk Assessment
  • Recurrence
  • Oncology & Carcinogenesis
  • Neoplasm Staging
  • Neoplasm Invasiveness
  • Middle Aged
  • Maximum Tolerated Dose
  • Male