Drug Shortages Roiling Oncology Practices, Impinging on Patient Care

The alternative, Fusilev, costs about ten times as much as leucovorin. And Medicare reimburses only $750 of the $1,200 cost for Fusilev, said Dr. Kovach, a member of the Association of Community Cancer Care Centers (ACCC) board of trustees. For many patients, the practice would "eat the loss." Other patients were sent to the hospital outpatient department for treatment. The shortage seems to have lessened for the time being, but reimbursement continues to be an issue, said Dr. Kovach.

The leucovorin shortage has "impacted many colorectal cancer regimens," at the Maine Center for Cancer Medicine in Scarborough, said Steven L. D’Amato, a clinical pharmacy specialist, in an interview. "Clinics like ours lose money with every dose administered, but we’ve done this to maintain patients’ treatment schedules," said Mr. D’Amato.

"With leucovorin, we literally decide how much we have every day," said Dr. Neuss. Patients are prioritized to receive the drug based on whether administration would be curative. His practice has managed to procure adequate supplies of Fusilev, but it is, as noted, much more expensive.

And oncologists "really don’t know" whether Fusilev is equivalent, Dr. Neuss said. The FDA also warns on its shortage page that "there is potential for dosing errors when interchanging leucovorin and levoleucovorin (Fusilev)."

Forced to Alternatives

Similarly, there is an alternative to IV etoposide – an oral version. But with oral administration, "myelosuppression can be more erratic," said Dr. Lawrence Einhorn, a past president of ASCO and a distinguished professor and Lance Armstrong Foundation Chair in Oncology at Indiana University, Indianapolis, in an interview on the ASCO Web site. "Oral etoposide is a substitute, but a poor substitute for IV etoposide," he said.

Dr. Neuss said that his practice had been doubling the dose of the oral version as a substitute. "Is that the exact right conversion? I’m not sure," he said.

There are four manufacturers of the injection form: Teva, Bedford, APP, and Bristol-Myers Squibb. Because Teva has halted production, the FDA has worked with the others to increase production, said Capt. Jensen.

Mr. D’Amato said that the Maine Center is no longer experiencing etoposide shortages, but that getting doxorubicin has been a challenge. The shortage is starting to alleviate, but the lack of the therapy has affected investigational protocols and "all of our anthracycline-containing regimens," he said.

The situation has been more dire in Cincinnati, said Dr. Neuss. His practice has been unable to find an adequate supply. "We hold it back for patients that are getting curative therapy," he said.

Mr. D’Amato also notes recent shortages of bleomycin, desmopressin, and heparin. "Heparin flush solutions are still not available to us, so we prepare our own from higher concentrations of heparin. This is time consuming and also costly," he said.

And, the Maine Center just began experiencing problems getting melphalan tablets (Alkeran), which were produced by GlaxoSmithKline but will now be manufactured by ApoPharma. "They have no release date for the product, which is very problematic for existing patients being treated for multiple myeloma," said Mr. D’Amato.

Pediatric oncology seems to be hit particularly hard, as the intent for most children is to cure them of their cancer. Thus, a shortage could mean the difference between life and death. "I think those children need to be protected," said Dr. Neuss.

In an interview with ASCO’s Web site, pediatric oncologist and ASCO President-Elect Michael Link said that there are few acceptable alternatives for many of the therapies used in children. "Almost all children are treated on clinical trial protocols, and have been for many years, so we have a very large evidence base for many of the common drugs that we use – but are lacking evidence for substitutions, particularly in complex multi-drug regimens," Dr. Link said.

Where Next?

In early November, ASCO, ASHP, the American Society of Anesthesiologists, and the Institute for Safe Medication Practices convened a summit to talk about causes of the shortages and to discuss potential solutions. The FDA and many drug manufacturers – including APP, Bedford, Hospira, and Teva, which had the most shortages in 2010 – attended the meeting.

According to a statement, the FDA told attendees that it had managed to prevent 24 shortages in the past year by working with the industry.

The ASHP said that work groups had been formed and would continue to develop action plans to "carry out the summit’s recommendations."

In early December, Sen. Amy Klobuchar, a Minnesota Democrat whose district includes the Mayo Clinic, wrote to FDA Commissioner Margaret Hamburg, urging an "immediate solution to the shortage of chemotherapy drugs."