Temozolomide (TMZ) is the chemotherapy drug approved by the FDA to increase survival in
glioblastoma (GBM) patients beyond surgical resection and radiation therapy alone. Give its
activity in astrocytomas, TMZ is commonly used in grade III anaplastic astrocytoma (AA) as
well. Both grade III AA and grade IV GBM are high grade gliomas (HGG). The short half-life of
this drug and known oscillations in DNA damage repair make it an ideal candidate for
chronotherapy.
Chronotherapy is the improvement of treatment outcomes by minimizing treatment toxicity and
maximizing efficacy through delivery of a medication according to the timing of biological
rhythms within a patient. Chronotherapy has improved outcomes through the reduction of side
effects and increase in anti-tumor activity for a variety of cancers, but has never been
applied to the treatment of gliomas.
Based on the preliminary preclinical data for chronotherapeutic TMZ treatment of intracranial
glioma xenografts and the success of chronotherapy in the treatment of other cancers, the
invesitgators hypothesize that the timing of TMZ treatment will alter its efficacy and
toxicity.