Optimal dosing for TMZ: 1 hour prior to RT versus bedtime

In clinical trials, temozolomide (Temodar) has been administered 1 hour prior to radiotherapy; however, most medical oncologists prescribe dosing at bedtime. Is there a difference in dosing (1 hour prior to radiotherapy vs bedtime) with tempzolomide plus radiotherapy for glioblastoma multiforme (GBM)? —Gayle Groshko, RN, BSN, OCN

Temozolomide, or TMZ, (Temodar) capsules should be taken with a glass of water, and given that absorption can be influenced by food, it should be taken on an empty stomach or at bedtime to reduce episodes of nausea or vomiting. In addition, TMZ should not be administered with other medications through the same IV line, which prohibits IV injection of radioactive materials. A review of existing literature does not demonstrate a significant difference between giving TMZ 1 hour prior to RT versus bedtime dosing in patients receiving combination therapy with RT for GBM, but studies have indicated a synergistic effect may be experienced with the combination of RT, arsenic trioxide, and TMZ. The administration of RT followed by arsenic trioxide and TMZ demonstrated striking synergy in U251T human glioma cell.

TMZ is an antineoplastic or alkylating agent (triazene) approved for the treatment of newly diagnosed, high-grade glioma, glioblastoma multiforme (a severe form of brain cancer). Temozolamide received accelerated approval in 1999 for the refractory anaplastic astrocytoma which later lead to a full approval based on results in adults with newly diagnosed glioblastoma multiforme. During a phase III study conducted by the European Organization for Research and Treatment of Cancers in patients with newly diagnosed GBM, the safety and efficacy of TMZ was established in 573 patients who were randomized to either TMZ + radiotherapy (RT) or RT alone. It was identified that those who received TMZ + RT treatment required prophylaxis against pneumocystsis carini pneumonia despite lymphocyte count and this was to continue until the recovery of lymphocytopenia was established. —Abinbola Farinde, PharmD, MS, BCPP, CGP, LCDC, PM/PRC, FACP, FACA, FNAP, Rsci, ARSPharmS

 

REFERENCES

·     1. Miglierini P, Bouchekoua M, Rousseau B, et al. Impact of the per-operatory application of GLIADEL wafers (BCNU, carmustine) in combination with temozolomide and radiotherapy in patients with glioblastoma multiforme: efficacy and toxicity.  Clin Neurol Neurosurg. 2012;114(9):1222-1225.

·     2. Portnow J, Gaur S, Synold TW. A clonogenic study of arsenic trioxide (ATO) and temozolomide (TMZ) together and in combination with radiation therapy (RT) in a human glioma cell line. J Clin Oncol (Meeting Abstracts). 2006;24(18 suppl):11506.