Clinicians, Cooperative Groups Work through Leucovorin Shortage
A shortage of the chemotherapy drug leucovorin
is raising some concern about patient care and the conduct of clinical trials, researchers and patient advocates have reported in recent weeks.
Although it is used to treat several cancers, leucovorin in combination with another chemotherapy drug, fluorouracil (often called 5-FU), is particularly important as part of the first-line therapy in patients with metastatic colorectal cancer and adjuvant therapy for earlier stage disease, explained Dr. Meg Mooney, head of Gastrointestinal and Neuroendocrine Cancer Therapeutics in NCI's Division of Cancer Treatment and Diagnosis.
Leucovorin calcium (Image courtesy of Bedford Laboratories)
It's unclear whether the shortage has had a demonstrable impact on patient care across the country. According to Kate Murphy from the Colorectal Cancer Coalition, the organization has not received many calls from patients reporting problems with their care because of lack of access to the drug.
“We've been hearing it more from the people in the clinical trials who are concerned about amending protocols,” Ms. Murphy said. Even so, she added, that is no guarantee that more wide-spread issues won't arise.
Managing the Shortage
NCI's Cancer Therapy Evaluation Program (CTEP) has provided general instructions to Cooperative Groups conducting CTEP-supported clinical trials on how to address the leucovorin shortage with regard to their specific protocols.
At Fox Chase Cancer Center in Philadelphia, the shortage initially “caused a fair amount of scrambling,” said Dr. Steven J. Cohen, a lead investigator on colorectal cancer trials at the center. The Eastern Cooperative Oncology Group, which runs a large number of colorectal cancer trials, quickly got word to facilities about the shortage, Dr. Cohen noted, so the staff worked with the pharmacy to secure enough levoleucovorin (Fusilev), an alternative form of leucovorin, to meet patient demand. Although levoleucovorin is not approved by the FDA for the treatment of colorectal cancer, it is often used off-label to treat it, according to a clinical alert issued by the American Society of Clinical Oncology.
“We wanted to make sure that for patients coming in to receive standard therapy, we had something for them,” he said. Sometimes that means alternating between standard leucovorin and levoleucovorin. Although dosing differences are an issue with levoleucovorin, the larger concern may be its vastly higher price tag, which is approximately 60 times higher than the generic leucovorin, Dr. Cohen said.
The experience differs from facility to facility, though. At Swedish Cancer Institute in Seattle, the leucovorin supply has been stable to date and has not had an impact on patient care or clinical trials, said Dr. Philip Gold, program leader of gastrointestinal cancers at that institute.
What's Behind It?
The shortage appears to have been brought on by manufacturing interruptions. Two companies produce leucovorin, Bedford Laboratories and Teva Pharmaceuticals. According to the most recent statement from Bedford, released nearly 5 weeks ago, supply interruptions of its leucovorin product are due to ongoing efforts at its Ohio manufacturing facility to expand production capacity.
“We anticipate resolution of these issues in the near future. Until such time, we will work diligently to fulfill our order commitments,” the December 18 statement said.
Teva has had no manufacturing issues that would slow production of its leucovorin product, according to a company spokesperson. However, in response to the shortage it has ramped up production and is releasing product as frequently as it can, the spokesperson said.