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

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

  • Blood. 2002 Mar 15;99(6):2241-4. doi: 10.1182/blood.v99.6.2241.
Lucio Tentori 1 Carlo Leonetti Marco Scarsella Giulia d'Amati Ilaria Portarena Gabriella Zupi Enzo Bonmassar Grazia Graziani
Affiliations

Affiliation

  • 1 Department of Neuroscience, University of Rome Tor Vergata, Via di Tor Vergata 135, 00133 Rome, Italy. [email protected]
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.

Figures
Products