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Blood, 15 March 2002, Vol. 99, No. 6, pp. 2241-2244
BRIEF REPORT
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, and
Grazia Graziani
From the Department of Neuroscience, University of Rome
Tor Vergata; Istituto Dermopatico dell'Immacolata, Rome; Experimental
Chemotherapy Laboratory, Regina Elena Cancer Institute, Rome; and
Department of Experimental Medicine and Pathology, University of Rome
La Sapienza, Italy.
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.
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