New Cancer Treatments : Off-Label Drugs

by National Cancer Institute

(Page 5 of 6)

Off-label use of drugs is widespread in cancer treatment for several reasons. Some cancer drugs are found to be effective against a variety of tumor types.

The mechanism of action of a drug or biologic (the way it works in the body) often suggests that it might be effective against tumor types other than those for which it is approved.

For example, cisplatin (brand name, Platinol®) works to halt the uncontrolled growth of cancer cells by interrupting the copying of DNA in growing cells. Because uncontrolled cell growth is part of most cancers, cisplatin is often used in the treatment of thyroid and lung cancers although it is only approved to treat bladder, testicular and ovarian cancers.

Some cancer drugs are approved because they effectively act on a specific biological target present in a particular type of tumor. Examples of such targeted drugs include:

imatinib mesylate or STI571 (brand name Gleevec™), which blocks the bcr-abl protein in chronic myelogenous leukemia,

trastuzumab (brand name Herceptin®), which blocks the HER 2 protein in breast cancer, and

tamoxifen (brand name Nolvadex®), which blocks the estrogen receptor in breast cancer.

However, once a drug is on the market further research may show that it also acts on different biological targets present in other kinds of cancer. Doctors may then begin to use the drug off label to treat those other cancers.

Cancer chemotherapy often involves the use of multiple drugs.

Multiple-drug treatment regimens have been shown to be effective in several types of cancer, including lymphoma, leukemia, bladder, testicular, and breast cancer. The regimens might include one or more drugs not approved specifically for that disease. Also, the FDA generally does not approve multidrug regimens themselves, in part because such regimens are so numerous as to make separate approvals impractical. Multidrug regimens change over time as doctors try different combinations and observe which regimens seem to produce the greatest benefit for patients.

Cancer treatment is always evolving.

Researchers continually conduct studies to determine new uses for already marketed drugs and to find effective combinations of drugs for new indications. The results of these studies are published in peer-reviewed medical journals. When a new treatment approach seems to produce better outcomes for patients, other doctors adopt it and it may become a new standard of care.

Can off-label drug use be harmful?

Use of a drug off label may cause harm when the drug's effect against a kind of cancer has not been demonstrated and there is no medical reason to believe the drug might be an effective treatment for that kind of cancer. All drugs have side effects; the side effects of cancer drugs vary depending on the kind of cancer being treated. When a drug's effect against a type of cancer has not been demonstrated, and its side effects are unknown, the possible risks of giving the drug may outweigh the possible benefits.

For example, the FDA approved the use of Gleevec to treat chronic myelogenous leukemia (CML). However, as of November 2001, its effect against chronic lymphocytic leukemia (CLL) had not been studied. The biological process that leads to the development of CLL is quite different from that which causes CML. Currently, there is little scientific data to support using Gleevec to treat CLL. Furthermore, it is not known what side effects the drug might cause in patients with CLL. For these reasons, the off-label use of Gleevec to treat CLL is generally not advised.

Will my health insurance cover drugs used off label for cancer treatment?

Some managed care organizations and health insurance providers decline to reimburse the cost of drugs used off label to treat cancer. Some insurers argue that when a drug is used for an unapproved indication, the use is experimental and therefore, excluded from coverage.

However, because changes frequently occur in the standard of care for cancer treatment, some insurance providers may be unaware of new combination drug regimens or new uses for approved drugs. In some cases, insurers may attempt to limit a doctor's choice of drugs to those that are lower in cost.

Since drugs used off label are often the standard of care for a particular kind of cancer, insurers' denial of coverage for such treatment means that patients may not receive what their doctors consider the best available treatment for their disease. To address this problem, federal and state lawmakers have passed laws that require coverage of off-label drug use for cancer treatment when the use is documented in certain authoritative drug reference books or in the medical literature.

Medicare coverage policy is not binding on private health insurance providers, although some insurers have adopted coverage policies consistent with Medicare's. Many states have passed laws or issued regulations requiring state-regulated private health insurers to provide coverage similar to Medicare's for off-label drug use in cancer treatment. However, organizations (usually large companies) funding their own health insurance coverage are exempt from these state laws and regulations, although many comply voluntarily.

The complexity of the laws and regulations governing health insurance coverage means there is no simple answer to the question of whether your own health plan covers drugs used off label for cancer treatment. When considering off-label drug use, you and your doctor should carefully check your plan's coverage policy.

If coverage is initially denied, it may be helpful for the doctor to provide the insurer with copies of peer-reviewed journal articles or other documents supporting the proposed off-label use.

What questions should I ask my doctor about off-label drug use?

The following are some questions you may wish to ask your doctor about off-label drug use in cancer treatment.

• What evidence is there to support the off-label use of this drug to treat the type of cancer that I have?
• Is the off-label use of this drug likely to be more effective that the use of an approved drug?
• What are the risks and benefits of off-label treatment with this drug?
• Will my health insurance cover off-label treatment with this drug?
• If my treatment involves a multidrug regimen and one of the drugs is being used off label, will my health insurance cover it?

What states require insurance coverage of off-label cancer drugs?

As of November 2001, the following states required some state-regulated health insurance providers to cover the off-label use of FDA-approved drugs for cancer treatment. Except where indicated, state law requires the coverage.

Although the wording of these laws varies from state to state, most require off-label uses to be covered when documented in authoritative drug reference books. Many, but not all, laws also require coverage when an off-label use is documented in the peer-reviewed medical literature.

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