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mesothelioma chemotherapy

Off-Label Drugs for Mesothelioma Treatment

What is off-label use?

Off-label use refers to the use of an approved treatment for any purpose, or in any manner, other than what is described in the treatment's labeling. Off-label use of an approved treatment is not the same as expanded access or special exemption, which are mechanisms allowing patient access to investigational treatments not yet approved by the FDA.

Off-label use of drugs is common in cancer treatment, although no one is sure of how common. The medical journal Lancet published a survey of studies finding between 6% and 33% of chemotherapy drugs are used off-label.

New treatments can be legally marketed in the United States only after approval by the U.S. Food and Drug Administration (FDA). Approval is the final stage of a multi-year process of study and testing to establish that the new treatment is safe and effective for the proposed use.

Any given cancer treatment rarely receives approval for general use against cancer. Instead, a treatment is approved for use in treating a specific stage of a particular kind of cancer, for which it has been tested in patients. The specific approved use is called an indication. The indication is described in the labeling for the drug or biologic, which consists of a printed insert included in the treatment's packaging. The insert also describes in detail the chemical composition of the treatment, how it works in the body, and the possible adverse effects of taking it.

However, the FDA - although responsible for ensuring that a treatment is safe and effective for the specific approved indication - does not regulate the practice of medicine. This means that once the FDA approves a treatment, licensed physicians can prescribe it for any purpose they consider medically appropriate.

Off-label uses may include giving an approved treatment:

  • for a disease other than the disease it is approved for,
  • at a different dose or frequency than specified in the product's labeling, or
  • to treat a child when the product is approved to treat adults.


An off-label use of a product can cease to be off label if the product's maker submits a supplemental application and obtains FDA approval for the new use. The FDA encourages, but does not require, drug makers to do this.

To submit a supplemental application, the drug maker must conduct studies to show that the product is safe and effective for the proposed new use. Unless the drug company expects to gain a significant commercial benefit from expanded approval of a drug already on the market, it may decide not to invest time and money in such additional studies.

Why is off-label use of drugs so common in mesothelioma treatment?


A 1991 study by the U.S. General Accounting Office found that one-third of the drug treatments performed by cancer doctors were off-label; more than half of cancer patients received at least one drug for an off-label indication. A 1997 survey of 200 cancer doctors by the American Enterprise Institute and the American Cancer Society found that 60 percent of them prescribed drugs off-label. Frequently the standard of care for a particular type or stage of cancer involves the off-label use of one or more drugs.

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.

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.
The regimens might include one or more drugs not approved specifically for mesothelioma. 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.

Mesothelioma 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.

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.

Congress passed a law in 1993 requiring Medicare to cover off-label drugs used in cancer treatment when the use is supported by:

  • a citation in at least one of the following authoritative drug reference books.
    • The American Society of Health-System Pharmacists' American Hospital Formulary Service (AHFS). There is a regularly updated online version.
    • U.S. Pharmacopeia Drug Information
  • two or more peer-reviewed articles published in respected medical journals.

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 mesothelioma?
  • 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?

 

This website is sponsored by Brad Cooper* of The Cooper, Hart, Leggiero, & Whitehead, PLLC. Cooper, Hart, Leggiero, & Whitehead is located in The Woodlands, Texas (Greater Houston Area) and can be reached toll free at 1-800-998-9729 for more information on mesothelioma. Brad Cooper is not a medical doctor. The information on these pages is for the education of mesothelioma patients and their families regarding potential medical and legal options. Patients are advised to consult with a medical doctor.

*  Licensed by the Supreme Court  of Texas.

 

 

 

The use of chemotherapy in patients with advanced malignant pleural mesothelioma: a clinical practice guideline.

Advances in the systemic therapy of malignant pleural mesothelioma

Kinase Inhibitors for Mesothelioma Treatment

journal abstracts

Active symptom control with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma (MS01): a multicentre randomised trial

The second wave in kinase cancer drugs

Cisplatin and vinorelbine first-line chemotherapy in non-resectable malignant pleural mesothelioma


Cytoreductive surgery and intraperitoneal chemotherapy for peritoneal mesothelioma.