Temozolomide
DESCRIPTION
Temozolomide is a cytotoxic agent of the imidazotetrazine class. It is a second generation alkylating agent and a methylating agent. While chemically related to another methylating agent, dacarbazine (DTIC), unlike DTIC, it does not require hepatic metabolism for activation. Administered orally or by injection, temozolomide is spontaneously hydrolyzed to its active state with rapid, near-100% bioavailability even in oral form. Temozolomide enters the spinal fluid and its cytotoxicity is thought to be primarily due to alkylation of DNA but, as with other methylating agents (i.e., procarbazine, streptozotocin and DTIC), it forms no DNA crosslinks. Temozolomide has activity against a variety of solid tumors and demonstrates minimal, non-cumulative myelosuppression that is rapidly reversible
An example of a preparation of temozolomide is Temodar®.
REFER TO DECISION SUPPORT TREE
POLICY
Temozolomide for the treatment of the following is considered medically necessary if the medical appropriateness criteria are met: (See Medical Appropriateness below.)
Anaplastic astrocytoma
Glioblastoma multiforme
Melanoma
Temozolomide for the treatment of other conditions/diseases is considered investigational. (See Applicable Tennessee State Mandate Requirements below.)
MEDICAL APPROPRIATENESS
Temozolomide for the treatment of ANY ONE of the following is considered medically appropriate if the following criteria are met:
Anaplastic astrocytoma with ALL of the following:
Individual is 18 years of age or older
Disease is refractory (i.e., disease progression on drug regimen containing nitrosurea and procarbazine)
Glioblastoma multiforme with ALL of the following:
Individual is 18 years of age or older
Disease is newly diagnosed
Initial treatment concomitant with radiotherapy (Note: Once temozolomide is initially given concomitantly with radiotherapy, it may be used as an adjuvant maintenance treatment)
Melanoma with ALL of the following:
Individual is 18 years of age or older
Disease is metastatic
Treatment is monotherapy
APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS
Tennessee State law requires coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is relative to life-threatening illnesses, such as cancer, AIDS, and coronary heart disease and recognized in one of the standard reference compendia (As defined in the statute: The United States Pharmacopoeia Drug Information, The American Medical Association Drug Evaluations, & The American Hospital Formulary Service Drug Information) or in the medical literature. This law is applicable to all fully insured members. The law is not applicable to self-funded accounts, but coverage for off-label uses may be provided based on the contractual agreement.
The NCCN Drugs & Biologics Compendium recognizes the use of temozolomide for additional uses beyond the FDA-approved labeling in the treatment of the following conditions (the NCCN Drugs & Biologics Compendium/ NCCN Clinical Practice Guidelines contains detailed recommendations):
Bone cancer - Ewing’s sarcoma
Central nervous system cancers
Metastatic central nervous system lesions (i.e., Brain metastases)
Primary central nervous system tumors (i.e., Adult low-grade infiltrative supratentorial astrocytoma/oligodendroglioma [excluding pilocytic astrocytoma], anaplastic gliomas, primary central nervous system lymphoma)
Neuroendocrine tumors - Islet cell tumors
(Note: NCCN rates the use of temozolomide in neuroendocrine carcinoid tumors for management of regional/mesenteric lymph node, lung, or liver metastases in individuals with carcinoid syndrome, clinically significant tumor burden, significant progression, or local effects as an NCCN category 3; thus, these indications are not included among the list of state mandate covered conditions/diseases.)
NHL - Mycosis fungoides/Sézary syndrome
Soft tissue sarcomas
Extremity/trunk
Retroperitoneal/intra-abdominal
Solitary fibrous tumor/hemangiopericytoma
ADDITIONAL INFORMATION
For appropriate dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., The American Hospital Formulary Service Drug Information).
Well-designed, randomized, controlled trials with long-term follow-up are not available to determine long-term benefits of temozolomide for the treatment/prevention of other conditions/diseases.
SOURCES
Lexi-Comp Online. (2010). AHFS DI. Temozolomide. Retrieved November 4, 2010 from Lexi-Comp Online with AHFS.
MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2010). Temozolomide. Retrieved November 4, 2010 from MICROMEDEX Healthcare Series.
National Comprehensive Cancer Network. (2010). NCCN Drugs & Biologics Compendium™. Temodar®. Retrieved November 4, 2010 from the National Comprehensive Cancer Network.
U. S. Food and Drug Administration. (2010, April). Center for Drug Evaluation and Research. Product Information. Temodar® (temozolomide). Retrieved November 4, 2010 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021029s018lbl.pdf.
ORIGINAL EFFECTIVE DATE: 3/10/2005
MOST RECENT REVIEW DATE: 4/14/2011
ID_BT
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
Pharmaceutical Decision Support Tree
Temozolomide (Temodar®)
Is the individual 18 years of age or older?
If yes, go to question #2
If no, this does not meet medical necessity and/or medical appropriateness criteria
Does the individual have a diagnosis of refractory anaplastic astrocytoma (i.e., disease progression on drug regimen containing nitrosurea and procarbazine)?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #3
Does the individual have newly diagnosed glioblastoma multiforme that will be treated concomitantly with radiotherapy?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #4
Does the individual have glioblastoma multiforme that was treated initially with temozolomide and radiotherapy and now requires maintenance therapy?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #5
Does the individual have a diagnosis of metastatic melanoma and requests temozolomide monotherapy?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
This document has been classified as public information.