An ongoing shortage of some crucial chemotherapy drugs is driving up the cost of the products and forcing oncologists to scramble for supplies or to find therapeutically equivalent alternatives, if there are any.
In some cases, oncologists are creating a triage system whereby the patient who is most likely to be cured will receive the therapy that’s in short supply.
Periodic shortages of pharmaceuticals are not unusual, but a number of factors have converged to create a unique squeeze in oncology – one that clinicians see as a mounting public health threat.
Dr. Michael Neuss said that the shortage will become a crisis only "when the first high-profile patient dies." Despite active concern and action by the American Society of Clinical Oncology, the shortage hasn’t reached the crisis point yet, at least in the public’s eye, said Dr. Neuss, immediate past chair of ASCO’s Clinical Practice Committee and a physician in private practice with Oncology Hematology Care in Cincinnati.
"There is no smoking gun that makes this obvious to people," he said.
Dr. Neuss sees the invisible hand of the free market as a not-beneficial guiding force in the shortage. Once a shortage occurs, distributors buy up the supplies and essentially corner the market, he said, citing conversations with his purchasing agent. That results in inflated prices for purchasers who have no alternative.
And cancer patients who need the therapies ultimately suffer, said Dr. Neuss.
Many Drugs Affected
At press time, both the Food and Drug Administration and the American Society of Health-System Pharmacists were reporting shortages of many drugs, including cisplatin, doxorubicin (both lyophilized powder and solution for injection), etoposide solution for injection, leucovorin calcium lyophilized powder for injection, levoleucovorin (Fusilev) 50-mg single-use vials, and some sizes of vincristine.
Cytarabine injection (powder for reconstitution) was added to the list in mid-December, and there’s also an ongoing shortage of certain vial sizes of Procrit (epoetin alfa) because of a manufacturing-related recall that took place in September.
Recently, there have been shortages of cyclophosphamide, daunorubicin, epirubicin, fluorouracil, mitomycin, paclitaxel, and vinblastine, among other chemotherapeutics.
The FDA – which, according to its Web site, has a policy "to help prevent or alleviate shortages, primarily of medically necessary drug products, since these can have significant public health consequences" – is monitoring the shortages. The agency does "see an end to these shortages based on the plans reported by the manufacturers," said Capt. Valerie Jensen, associate director of the FDA’s Center for Drug Evaluation and Research Drug Shortage Program, in an e-mail.
But, she added, "many of these shortages involve older sterile injectable drugs, and we’ve continued to see a trend of increasing shortages developing over the past several years for this group of drugs."
Fewer companies are interested in making the low-profit injectables, and those firms that do go into the market have limited manufacturing capability, said Capt. Jensen. Many of the companies in the market have had issues with accessing raw materials, or problems meeting the FDA’s quality guidelines.
Then there’s the manufacturing itself. "Sterile injectables have a long manufacturing lead time and a complex process, and when one of the few firms making these products experiences a problem, a shortage almost always occurs, since it is extremely difficult for the remaining firms to keep up with demand," she said.
Leucovorin: Canary in the Coal Mine
One of the biggest players in injectables – and generics – is Teva Pharmaceuticals. In April, the company began a voluntary manufacturing hold at its Irvine, Calif., plant to update systems and processes. The plant was the primary manufacturing site for all its injectables. The stoppage has had a domino effect, shifting demand to other manufacturers. Some have managed, but the shortage continues – especially for leucovorin and etoposide.
Teva spokeswoman Denise Bradley said, "We continue to work towards resuming manufacturing at that facility," but gave no indication as to when that might occur.
Capt. Jensen said that Teva should be back online by April 2011. In the meantime, the FDA has looked for additional manufacturers for leucovorin, including those overseas, as it also had to do to manage a shortage of propofol, an anesthetic agent. The agency has not found a suitable overseas candidate, but is working with another generic manufacturer to "have their product ready for the U.S. market as soon as possible."
For now, though, clinicians are struggling to figure out how to make do. Dr. George Kovach, medical director at Iowa Cancer Specialists in Davenport, said that his practice has not been affected by other shortages, but that getting leucovorin has been a challenge. Financially managing the shortage has also been an issue, said Dr. Kovach in an interview.