Combined treatment with temozolomide and poly(ADP-ribose) polymerase inhibitor enhances survival of mice bearing hematologic malignancy at the central nervous system site

Lucio Tentori, Carlo Leonetti, Marco Scarsella, Giulia D'Amati, Ilaria Portarena, Gabriella Zupi, Enzo Bonmassar, Grazia Graziani

Research output: Contribution to journalArticlepeer-review

Abstract

Temozolomide (TZM) is a DNA-methylating agent that has recently been introduced into various clinical trials for treatment of solid or hematologic neoplasias, including brain lymphomas. In the current study, we have investigated whether the antitumor activity of TZM could be selectively enhanced at the central nervous system (CNS) site by intracerebral injection of a poly(ADP-ribose) polymerase (PARP) inhibitor. Mice were injected intracranially with lymphoma cells. The PARP inhibitor NU1025 (1 mg/animal) was delivered intracerebrally, whereas TZM was given as a single or a fractionated dose of 200 mg/kg by intraperitoneal administration. Results indicated that this drug combination significantly enhanced the survival of tumor-bearing mice and that this fractionated modality of treatment was the most effective schedule. Increased survival time was related to a marked reduction of tumor growth, as evidenced by histologic studies. Treatment with TZM alone was ineffective. This is the first report exploring in vivo the combination of TZM with PARP inhibitor for intracerebral neoplasias.

Original languageEnglish
Pages (from-to)2241-2244
Number of pages4
JournalBlood
Volume99
Issue number6
DOIs
Publication statusPublished - Mar 15 2002

ASJC Scopus subject areas

  • Hematology

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