BlueCross BlueShield of Tennessee Medical Policy Manual

Mitoxantrone (Systemic)

DESCRIPTION

Mitoxantrone is a synthetic antineoplastic anthracenedione structurally similar to the anthracyclines doxorubicin and daunorubicin. Its exact mechanism of action is unknown but it is a DNA-reactive agent. Mitoxantrone intercalates into DNA through hydrogen bonding causing crosslinks and strand breaks. Additionally, it interferes with RNA and is a potent inhibitor of topoisomerase II, an essential enzyme active in virtually every cellular DNA process. Mitoxantrone shows a cytotoxic effect on both proliferating and non-proliferating cultured human cells suggesting that it lacks cell-cycle specificity.

An example of a preparation of mitoxantrone is Novantrone®.

REFER TO DECISION SUPPORT TREE

POLICY

Mitoxantrone for the treatment of multiple sclerosis is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Mitoxantrone for the treatment of prostate cancer is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Mitoxantrone for the treatment of nonlymphocytic leukemia (ANLL) is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Mitoxantrone for the treatment of breast carcinoma is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Mitoxantrone for the treatment of non-Hodgkin’s lymphoma is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Mitoxantrone for the treatment of other conditions/diseases, including, but not limited to, the following: acute lymphoblastic leukemia and primary progressive multiple sclerosis is considered investigational. (See Applicable Tennessee State Mandate Requirements below.)

MEDICAL APPROPRIATENESS

Mitoxantrone is considered medically appropriate for the treatment of ANY ONE of the following:

Secondary (chronic) progressive, or progressive relapsing, or worsening relapsing-remitting multiple sclerosis
Prostate cancer with ALL of the following:

The agent is used in combination with corticosteroids
Initial palliative treatment of pain related to advanced hormone- refractory prostate cancer

Acute nonlymphocytic leukemia (ANLL) (includes myelocytic, promyelocytic, monocytic, erythroid) in adults (18 years or older) when used as combination therapy
Locally advanced or metastatic breast carcinoma when used alone or in combination with other agents
Non-Hodgkin’s lymphoma when used as a component of combination therapy

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.

Drugdex recognizes the use of mitoxantrone in the treatment of:

Children with acute myeloid leukemia when used as combination therapy
Liver carcinoma
Ovarian cancer

The NCCN Drugs & Biologics Compendium recognizes the use of mitoxantrone for additional uses beyond the FDA-approved labeling in the treatment of the following conditions (Refer to the NCCN Drugs & Biologics Compendium or NCCN Clinical Practice Guidelines for detailed recommendations):

Classical Hodgkin lymphoma
Lymphocyte predominant Hodgkin lymphoma

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).

No controlled studies were found in the published literature that validate the use of Mitoxantrone for the treatment of other conditions/diseases.

SOURCES

Drugs for breast cancer. (2005, January). Treatment Guidelines from The Medical Letter, 3 (Issue 29), 1-6.

Lexi-Comp Online. (2009). AHFS DI. Mitoxantrone hydrochloride. Retrieved July 16, 2009 from Lexi-Comp Online with AHFS.

MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2009). Mitoxantrone. Retrieved July 16, 2009 from MICROMEDEX Healthcare Series.

National Comprehensive Cancer Network. (2009). NCCN Drugs & Biologics Compendium™. Mitoxantrone. Retrieved July 16, 2009 from http://www.nccn.org/professionals/drug_compendium/mainpage.aspx.

U. S. Food and Drug Administration. (2008, August). Center for Drug Evaluation and Research. FDA Label Information. Novantrone®. July 15, 2009 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019297s030s031lbl.pdf.

ORIGINAL EFFECTIVE DATE: 11/1/2004

MOST RECENT REVIEW DATE: 12/12/2009

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

Mitoxantrone (Systemic) (Novantrone®)

Is the requested medication being used to treat acute lymphoblastic leukemia or primary progressive multiple sclerosis?

If yes, this does not meet medical necessity and/or medical appropriateness criteria

If no, go to question #2

Is the agent being used to treat secondary (chronic) progressive, or progressive relapsing, or worsening relapsing-remitting multiple sclerosis?