A randomized phase II and pharmacokinetic study of dacarbazine in patients with recurrent glioma

Vincent S. Rajkumar, J. M. Reid, P. J. Novotny, S. L. Safgren, B. W. Scheithauer, Steven P. Johnson, S. Nair, R. F. Morton, A. K. Hatfield, J. E. Krook, M. M. Ames, J. C. Buckner

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

We conducted a randomized phase II study to determine the efficacy of dacarbazine (DTIC) in recurrent gliomas. Patients were randomly assigned to receive either DTIC 750 mg/m2 IV day 1 every 28 days (Arm A) or DTIC 200 mg/m2 IV days 1-5 every 28 days (Arm B). Pharmacokinetics were studied in 6 patients on each arm using HPLC analysis. Thirty-nine patients (30 male, 9 female), ages 27-67 years (median 53) were entered on the study (20 on Arm A, 19 on Arm B). No objective responses were seen. Median time to progression was 3 months. Median survival was 8 months. Treatment was generally well tolerated. Major toxicities were grade 1-2 nausea (33%), lethargy (28%), diarrhea (15%), alopecia (15%), and grade 3 neutropenia (8%). Four patients on Arm A had mild self-limited episodes of intravascular hemolysis occurring immediately after drug infusion, the mechanism of which is unknown. Mean AUC for DTIC, HMMTIC (5-[3-hydroxymethyl-3-methyl-1-triazeno] imidazole-4-carboxamide), and MTIC (5-[3-methyl-1-triazeno] imidazole-4-carboxamide), in Arm A were 14.8, 0.17, and 1.15 mM min, respectively. Corresponding values for Arm B (on day 1 of 5) were 1.7, 0.06, and 0.29 mM min, respectively. The predicted HMMTIC and MTIC exposure over 5 days for Arm B, based on the day 1 data, is higher than with Arm A. We conclude that DTIC is well tolerated but does not have activity in patients with recurrent gliomas. The 5-day schedule appears less toxic, and pharmacokinetics studies show that it provides greater exposure to MTIC and HMMTIC compared to the one-day schedule.

Original languageEnglish (US)
Pages (from-to)255-261
Number of pages7
JournalJournal of neuro-oncology
Volume49
Issue number3
DOIs
StatePublished - Dec 1 2000

Keywords

  • Brain tumors
  • Chemotherapy
  • DTIC
  • Dacarbazine
  • Glioblastoma
  • Recurrent gliomas

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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    Rajkumar, V. S., Reid, J. M., Novotny, P. J., Safgren, S. L., Scheithauer, B. W., Johnson, S. P., Nair, S., Morton, R. F., Hatfield, A. K., Krook, J. E., Ames, M. M., & Buckner, J. C. (2000). A randomized phase II and pharmacokinetic study of dacarbazine in patients with recurrent glioma. Journal of neuro-oncology, 49(3), 255-261. https://doi.org/10.1023/A:1006454427026