
Temozolomide is a new chemotherapy agent, which is taken orally.  It is a prodrug, and is hydrolyzed [changed by the body] to the active agents once taken.  These are the same active agents that dacarbazine provides.  Dacarbazine, or DTIC, is an older, but intravenous, chemotherapy agent.  These two drugs are very closely related.
Temozolomide as a sole agent is an effective agent for Uterine LMS, giving a response rate around 40%, for a period of time.  It is not so effective against nonuterine LMS. However there is a clinical trial of temozolomide coupled with thalidomide [Thalomid] that is showing some promising results.

Temozolomide's main toxicities are nausea [well controlled with Zofran or Kytril] and myelosuppression [bone marrow suppression].  Being an oral tablet, it disrupts lives less than intravenous treatments do.

It has been called an optimal agent to develop in combination with other cytotoxic, biologic, and targeted therapeutics for patients with relevant malignancies. Temozolomide is sometimes paired with other agents. Thalidomide (Thalomid) exhibits antiangiogenic activity and other biological modulatory effects that may provide additive or synergistic [working with another agent] antitumor effects when given at the same time as another chemotherapy agent. A phase I/II study of thalidomide and temozolomide in the treatment of Uterine LMS is in progress. Preliminary results of this combination therapy in metastatic melanoma have shown significant antitumor activity, including some striking responses in brain metastases. It will be interesting to see if there is a preventative effect on the incidence of brain metastases in Uterine LMS.

In a study comparing the effects of Dacarbazine [DTIC] and Temozolomide therapy in melanoma patients: 
	* Temozolomide therapy improved health-related quality of life.
	* Systemic exposure (area under the curve) to the parent drug and the active metabolite, MTIC, was higher after treatment with oral temozolomide than after IV administration of DTIC. 
	* The conclusion was that Temozolomide demonstrates efficacy equal to that of DTIC and is an oral alternative for patients with advanced metastatic melanoma. 

Of note is the usefulness of Temozolomide in treating brain tumors.  Since it can penetrate the blood brain barrier, it might decrease the incidence of brain metastases in LMS, or at least be able to be used to treat such metastases.
