Temozolamide (TMZ)

Owners of pets with cancer frequently ask if there are orally administered alternatives to injectable chemotherapy drugs. Often this is out of misconception that oral drugs afford fewer side effects.  Unfortunately, any cytotoxic medication has the potential to cause adverse effects, regardless of route of administration.

Many owners also feel treating their pet with an oral chemotherapy drug will be a less stressful option for their pet.  Whether actual or perceived, if an owner feels their animal will experience distress or anxiety from an injection of a drug, they will seek another form of treatment, or potentially decide to not pursue treatment at all. The idea of their pet taking their chemotherapy as a “treat” is often a far more appealing and viable option.

downloadOwners also may be familiar with oral chemotherapy because they, or a friend or family member, have been prescribed such drugs themselves. As is the case for much of veterinary oncology, there are far more of such options available for people with cancer than for animals.

One such relatively unexplored option for veterinary patients with cancer is a drug called temozolamide (TMZ). TMZ is an oral alkylating chemotherapy agent of the imidazotetrazine family.

In people, TMZ is used to treat primary and metastatic brain tumors, melanoma, and cutaneous lymphoma. Its use in veterinary oncology has generally been restricted to treating relapsed or refractory lymphoma in dogs, however other tumor types could be responsive as well.

The metabolism and mechanism of action of TMZ are similar to those of dacarbazine (DTIC), which is a chemotherapeutic frequently prescribed in veterinary medicine. Unlike DTIC, which requires activation by the hepatic cytochrome p-450 system, TMZ is activated non-enzymatically via hydrolysis in the bloodstream. Another advantage of TMZ is that it is administered orally, whereas DTIC is given over a prolonged intravenous infusion (5-8 hours) or as a daily bolus for 5 consecutive days.

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One study examined treating dogs with relapsed or refractory lymphoma with TMZ combined with either doxorubicin or dactinomycin. The response rates, remission duration, and frequency of gastrointestinal side effects were comparable to dogs treated with combinations of either DTIC and doxorubicin or DTIC and dactinomycin. However, the frequency of hematological toxicity was greatly reduced. The ease of administration of TMZ and less chance of causing leukopenia or thrombocytopenia (as compared to DTIC) makes it an attractive option for treating dogs with relapsed or refractory lymphoma.

TMZ has been evaluated for use in cats with a variety of tumor types.  Responses to treatment were detected in feline patients with refractory lymphomas, however unacceptable and unanticipated toxicities occurred, therefore the study was terminated prior to target enrollment. Further investigation into the use of TMZ in cats is therefore carefully warranted.

Having options is important to owners of pets with cancer. It’s important to listen to their goals and expectations and devise a treatment plan that provides the best chance of success, but also empowers owners in the decision making process. If you have a patient you believe could be a candidate for treatment with oral TMZ treatment, please do not hesitate to contact the Hope VS Oncology Department at 610-296-2099 or email: [email protected]

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