Doctors and patient advocates say a shortage
of a key drug for colorectal cancer could deprive thousands of patients of
appropriate treatment and stall the testing of new experimental drugs.
Leucovorin, a modified B vitamin, has been a key ingredient in
chemotherapy regimens for 30 years, ever since studies found it tripled the
number of patients whose tumors shrank when given another drug, called
5-flurouracil. A drug cocktail of 5FU and leucovorin is now a backbone of colon
cancer chemotherapy. Newer drugs like Erbitux and Avastin have never been
tested without it.
But leucovorin, which is generic, is made by only two companies:
Teva Pharmaceuticals of Jerusalem and Bedford Laboratories, a Bedford, Ohio,
subsidiary of the German drug giant Boehringer Ingelheim. In November, the Food
and Drug Administration said that both companies were unable to make an
adequate supply, but hard information about the shortage has been difficult to
obtain, beyond what is posted on the FDA Web
More than 140,000 Americans are diagnosed with colorectal cancer
annually, but it is not clear how many are affected by the shortage, as the
degree of rationing varies. M.D. Anderson Cancer Center says it anticipated the
shortage and just received a bulk shipment, but at the University of
California, San Francisco, "the average patient" is not getting leucovorin,
says UCSF oncologist Alan Venook, and a committee meets weekly to decide how to
use the existing supply.
"This is a very serious and scary situation for patients," says
Kate Murphy, director of research communication for the Colorectal Cancer
Coalition, a patient advocacy group. Murphy has personally survived three bouts
of colon cancer over a 25-year period, the most recent last year.
"There are no answers at the FDA, and there are no answers at the
manufacturers as to what is causing the shortage or how soon it might be
resolved." Murphy says. "With no leucovorin in the pipeline, patients are just
faced with no good alternatives."
Multiple requests for comment by Forbes to Teva were unanswered,
and Boehringer had no immediate comment. The FDA is "aware that leucovorin
injection is in shortage due to manufacturing delays," says Karen Riley, an FDA
spokeswoman. "Bedford and Teva are both releasing product currently, and we are
continuing to monitor this situation," she says.
But the Web site of the American Society of Health-System
Pharmacists says that leucovorin powder for injection from both Teva and
Bedford is on back order, that the companies "cannot estimate a release date,"
and that "the manufacturers will not provide a reason
for the shortage"
On an Internet chat room support group called the
Colon Club, one patient wrote of not receiving any leucovorin at a
scheduled infusion of the cancer drug Eloxatin, made by Sanofi-Aventis.
"Neither the distributor nor the manufacturer had any in stock." Another
patient reported being switched from Eloxatin to Xeloda, a pill made by Roche
that does not require intravenous leucovorin. Camptosar, a competing drug from
Pfizer, is also administered with leucovorin. Sanofi-Aventis is "aware of the
situation," says spokeswoman Noelle Boyd. "We are currently looking into the
implications both from a research and a commercial perspective."
The Eastern Cooperative Oncology Group (ECOG), an independent
group of academic cancer doctors that has played a key role in testing new
cancer medicines, started hearing from hospitals that they were almost out of
"We've been fielding phone calls from institutions that are
running out," says Albert Benson, head of clinical investigation at the Robert
H. Lurie Cancer Center and chairman of an ECOG committee that oversees
colon-cancer drug studies. "There may be institutions that have a good supply,
but it is getting harder and harder to find. This is going to affect a lot of
people, and we need to have some answers."
ECOG and other similar clinical trial groups are holding an
emergency conference call Tuesday to try to figure out how to handle ongoing
clinical trials if more leucovorin does not emerge. These groups are running
100 studies of cancer drug regimens that might improve on current cancer drug
regimens. Genentech says the shortage is not yet affecting research on its drug
"This is starting to be an issue nationally," says Leonard Saltz,
a leading colon cancer doctor and researcher at Memorial Sloan-Kettering Cancer
Center in New York. He warns that there is short supply for "a number of
drugs," including vinblastine for lymphoma, and dexraxozane, used to protect
the heart from another chemotherapy, doxorubicin.
In a blog post on the
Web site of HemOnc Today, a trade publication for cancer doctors, oncologist
Noelle LoConte of the University of Wisconsin writes that there are ongoing
shortages of other drugs, including cyclosporine and doxorubicin.
"There is no clear endpoint in the shortage," she writes, "and
clearly some patients need it without question." She adds that as rumors of the
shortage spread, some doctors have stockpiled the drug. "One of my partners was
at a site yesterday which had two years of leucovorin stored! The drug will
likely expire before they can use it all!"
UCSF oncologist Venook says he is not sure leucovorin is
necessary. It was added when 5FU was a new drug, and its not clear whether
there will be a real impact from removing it. Still, the shortage is leading to
general fears about access to generic cancer drugs.
"I've never heard of anything like it," says Michael Katz, a
cancer survivor who is chair of a committee of patients that advises ECOG. He
worries that the leucovorin shortage is a "red flag" that the cheap generic
drugs cancer doctors use in addition to the pricey drugs like Avastin, made by
Genentech and Roche, and Erbitux, from Eli Lilly and Bristol-Myers Squibb.
"This could be something that could occur much more frequently
with generic drugs, because the margins of generic drugs are so thin. And many
of the drugs that are the most important drugs in the cancer armamentarium are
the drugs that have gone off patent," says Katz. He wonders why there is no
system to catch such shortages and prevent them from harming patients or
halting clinical trials.
Katz asks, "How many drugs are out there that are just being
produced by the grace of God?"