National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
February 8, 2011 • Volume 8 / Number 3

FDA Update

Another Radioactive Tracer Approved for Bone Scans

As a first step toward solving the ongoing shortage of a drug used in bone scans, called Technetium-99m (Tc-99m), NCI has won Food and Drug Administration (FDA) approval for a radioactive positron emission tomography (PET) tracer called Sodium Fluoride F18. This drug was originally approved in 1972 but was withdrawn in 1975, when a less-expensive alternative became available. This new approval covers a different dose and strength.

Radioactive tracers are used for bone scans with PET to diagnose skeletal metastases from primary cancers elsewhere in the body. Bone metastases are a serious issue for many types of cancer, particularly for patients with breast and prostate cancers.

One reason NCI submitted a New Drug Application (NDA) for Sodium Fluoride F18 was to make it possible for manufacturers to develop cheaper generic versions of the drug. The manufacturing of generic drugs could not begin until the NDA had been approved.

“We put together the NDA, and now that the drug has been approved, academic and commercial sites can file an abbreviated new drug application for generic versions,” said Dr. Paula M. Jacobs, acting associate director of NCI’s Division of Cancer Treatment and Diagnosis.

FDA approval is also important for reimbursement, noted Dr. Jacobs. The Centers for Medicare & Medicaid Services released a statement this week that it would reimburse for Sodium Fluoride F18 when patients are enrolled in a registry, and this could lead private insurers to do so, as well.

Until now, the only approved radioactive tracer has been Tc-99m. Over the last 5 years, there have been widespread shortages of that drug, which is a decay product of molybdenum-99 (Mo-99). The shortages, which are expected to continue for several more years, have been caused by problems with the few aging nuclear reactors that manufacture Mo-99, according to information from NCI’s Cancer Imaging Program.

A shortage of Mo-99 that lasts more than a week or two leads to immediate market shortages and can prevent clinicians from obtaining medical scans that use this agent. In 2007, more than 2.5 million patients underwent bone scans. Although not all of these scans used Tc-99m, millions of patients each year undergo scans involving radioactive tracers, noted Dr. Jacobs.

“The new approval will certainly help with the supply of these drugs going forward, and it will facilitate reimbursement,” she said.

See a history and rationale behind NCI’s filing of a New Drug Application for Sodium Fluoride F18.

Rituximab Approved as Maintenance Therapy for Follicular Lymphoma

On January 28, the FDA approved rituximab (Rituxan) as a maintenance therapy for patients with follicular lymphoma who responded to initial treatment with rituximab in combination with chemotherapy. The approval is the drug’s sixth cancer indication since it was initially approved in 1997 as a second-line treatment for non-Hodgkin lymphoma (NHL). In addition to several NHL indications, rituximab is also approved for the treatment of chronic lymphocytic leukemia.

The FDA granted the new indication based on the international phase III PRIMA trial, which involved 1,200 patients. Those in the trial who responded to initial treatment with rituximab and chemotherapy, and who continued to receive rituximab every 2 months for the next 2 years, had a 46 percent improvement in progression-free survival compared with patients who did not receive the maintenance therapy. After 2 years, 82 percent of patients in the maintenance therapy arm compared with 66 percent of patients in the control arm were still alive with no progression of their disease.

The PRIMA trial results were presented last year at the American Society of Clinical Oncology’s annual meeting.

FDA Investigates Breast Implants and a Rare Lymphoma

The FDA is investigating a possible association between breast implants and a very rare form of cancer called anaplastic large cell lymphoma, or ALCL. Based on a review of the scientific literature and discussions with experts, the agency said that women with breast implants may have a very low but increased risk of developing ALCL compared with women who do not have breast implants. The announcement came in a January 26 news release.

At this time, there is not enough information available to determine whether the implants might be a cause of ALCL, and the FDA is not recommending breast implant removal in patients without symptoms or other abnormalities. Nevertheless, the FDA said it would work with breast implant manufacturers to update their product labeling materials for patients and health care professionals in the coming months.

To date, FDA scientists have learned of approximately 60 cases of ALCL in women with breast implants worldwide, though they said the actual number of cases could be difficult to determine. (An estimated 5 to 10 million women have breast implants.) The agency is working with the American Society of Plastic Surgeons and other experts to establish a registry of breast implant patients, which researchers could use to study the possible association.

“We need more data and are asking that health care professionals tell us about any confirmed cases they identify,” said Dr. William Maisel, chief scientist and deputy director for science in FDA’s Center for Devices and Radiological Health, in a statement.

ALCL is diagnosed in about 1 out of 500,000 women in the United States each year and appears in different parts of the body, including the lymph nodes and skin. ALCL located in breast tissue is found in only about 3 out of every 100 million women nationwide without breast implants.

“Health care providers should be aware ALCL in women with breast implants is a very rare condition,” said the authors of an FDA white paper on the subject. Currently, it is not possible to identify a type of implant (silicone versus saline) or a reason for implant (reconstruction versus aesthetic augmentation) associated with a smaller or greater risk, the authors added.

Some researchers have suggested that breast implant-associated ALCL may represent a new clinical entity with less-aggressive (indolent) behavior. However, in view of the small number of cases and the short median duration of follow-up, the FDA said it is premature to draw conclusions regarding the prognosis of ALCL in women with breast implants.

For more information see the FDA’s Questions and Answers about Anaplastic Large Cell Lymphoma (ALCL) and a Consumer Update.

The NCI Fact Sheet on breast implants is here.