Phase II trial of merbarone in patients with malignant brain tumors

Ummekalsoom R. Malik, Janice P. Dutcher, Geralyn Caliendo, Patrick A. LaSala, Robin Mitnick, Peter H. Wiernik

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The standard treatment for patients with primary malignant glioma includes surgical resection, radiotherapy, and nitrosourea. Despite this multimodality approach, adults with newly diagnosed glioblastoma multiforme (GBM) and high-grade astrocytoma have a median survival duration of 50 weeks and 150 weeks respectively. Chemotherapy has had a limited impact on the survival of these patients. Merbarone (5-phenylcarboxamide-2-thiobarbituric acid) is a nonsedating derivative of barbituric acid that crosses the blood brain barrier. Antitumor activity of merbarone has been described against L1210, B16 melanoma cell line and the M5076 sarcoma cells in phase I studies. Merbarone inhibits DNA synthesis and tumor growth by inducing single strand breaks in DNA. It also inhibits RNA and protein synthesis. We evaluated merbarone in a phase II trial in patients (pts) with recurrent or refractory GBM (7 pts) and high grade anaplastic astrocytoma (7 pts). Fourteen patients (nine males, five females) were treated with merbarone at a dose of 2000 mg per me per day by continuous intravenous infusion for 5 days every 3 weeks. Every patient received at least two cycles of treatment. No complete or partial responses were observed, although one patient had stable disease lasting 20 weeks. Our conclusion is that merbarone is ineffective against GBM and high-grade anaplastic astrocytoma at the dose and schedule in which it was administered in this trial.

Original languageEnglish (US)
Pages (from-to)159-162
Number of pages4
JournalMedical Oncology
Volume14
Issue number3-4
StatePublished - Sep 1997

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merbarone
Brain Neoplasms
Astrocytoma
Glioblastoma
Single-Stranded DNA Breaks
Experimental Melanomas
Survival
Blood-Brain Barrier
Intravenous Infusions
Glioma
Sarcoma

Keywords

  • Brain tumor
  • Glioblastoma multiforme
  • Merbarone

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Malik, U. R., Dutcher, J. P., Caliendo, G., LaSala, P. A., Mitnick, R., & Wiernik, P. H. (1997). Phase II trial of merbarone in patients with malignant brain tumors. Medical Oncology, 14(3-4), 159-162.

Phase II trial of merbarone in patients with malignant brain tumors. / Malik, Ummekalsoom R.; Dutcher, Janice P.; Caliendo, Geralyn; LaSala, Patrick A.; Mitnick, Robin; Wiernik, Peter H.

In: Medical Oncology, Vol. 14, No. 3-4, 09.1997, p. 159-162.

Research output: Contribution to journalArticle

Malik, UR, Dutcher, JP, Caliendo, G, LaSala, PA, Mitnick, R & Wiernik, PH 1997, 'Phase II trial of merbarone in patients with malignant brain tumors', Medical Oncology, vol. 14, no. 3-4, pp. 159-162.
Malik UR, Dutcher JP, Caliendo G, LaSala PA, Mitnick R, Wiernik PH. Phase II trial of merbarone in patients with malignant brain tumors. Medical Oncology. 1997 Sep;14(3-4):159-162.
Malik, Ummekalsoom R. ; Dutcher, Janice P. ; Caliendo, Geralyn ; LaSala, Patrick A. ; Mitnick, Robin ; Wiernik, Peter H. / Phase II trial of merbarone in patients with malignant brain tumors. In: Medical Oncology. 1997 ; Vol. 14, No. 3-4. pp. 159-162.
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