* Some mainstay generic chemotherapy drugs in short supply
* Slim profit margins offer little drugmaker incentive
* Clinicians face difficult treatment choices
By Debra Sherman and Julie Steenhuysen
CHICAGO, June 7 Cancer medicines desperately
needed by sick children and adults are in short supply,
undermining the ability of U.S. doctors to administer
treatments, top oncologists warned this week.
Many drugs are scarce because there is no incentive for
drugmakers to manufacture low-cost generics, which have slim
profit margins for pharmaceutical companies. Doctors do not
expect that equation to change any time soon, making them
scramble to find acceptable alternatives, or to ration or delay
treatment when they cannot.
Generic chemotherapy drugs are in particularly tight supply
at the nation's hospitals, including mainstay cancer treatments
such as cisplatin, doxorubicin, cytarabine and leucovorin.
"These are chestnuts. These are not old-fashioned drugs.
They remain incredibly important drugs which serve as the
backbone for treating many of the most common and treatable
cancers," said Dr. Robert Mayer of the Dana-Farber Cancer
Institute in Boston and a past president of American Society of
Clinical Oncology (ASCO) which held its annual meeting in
Chicago this week. (For full coverage, see: [ID:nN05141382] )
Cisplatin is used to treat testicular, bladder and ovarian
cancers that have spread. The drug, also used to treat lung
cancers, is sold under multiple brand names, originally by
Bristol-Myers Squibb (BMY.N). A generic form is sold by Teva
Pharmaceutical Industries Ltd TEVA.O, among others.
Doxorubicin, also available under multiple brands and as a
generic from Teva and others, is used to treat non-Hodgkin's
lymphoma, multiple myeloma, acute leukemias and other cancers.
Cytarabine, produced by Hospira Inc HSP.N and others, is
used to treat certain types of leukemia. Leucovorin, also sold
by Teva, is used along with certain chemotherapy drugs to treat
colorectal, head and neck and other cancers.
Dr. Michael Link, a pediatric oncologist at the Mayo Clinic
and current ASCO president, called it a disheartening crisis.
"Here we have highly effective drugs, they've been shown
they work and to think we don't have them available is almost
unconscionable," Link said. "We don't see an end in sight."
In some cases, doctors can substitute another drug for one
that is in short supply.
"It's still uncomfortable to say that this is ideally what
we'd like to do, but unfortunately we don't have it," Link
said. "You can imagine the conversation and I'm sure they're
going on all over -- doctors have to tell their patients or
their patients' parents that we can't give them the proven drug
because we don't have it."
For some of these medicines in short supply, there may not
be acceptable alternatives.
"One could say that substituting Pepsi for Coca-Cola
doesn't make a difference. Maybe it does and maybe it doesn't,"
Mayer said. "But more often it might be substituting 7-UP for
Coca-Cola, and that might make a difference."
Leucovorin, a form of folic acid that is used to enhance
the effectiveness of other chemotherapy drugs, is one example.
"This is the one that I hear the most about from my
colleagues. If you don't have it, you just have to omit it. It
certainly isn't in the best interest of patients. It is a very
inexpensive drug," Mayer said.
Sophia Parhas, a pharmacy manager at Children's Memorial
Hospital in Chicago, said if there is a shortage of the
generic, the hospital will often buy the branded product.
"We make some substitutions ... so doctors will go back and
forth between daunorubicin and doxorubicin, depending upon
which one is short," she said.
Another option is for doctors to flip the order that drugs
are given depending on the supply situation. Allen Vaida,
executive vice president of the Institute for Safe Medical
Practices, which has been tracking the shortage, said doctors
have also been forced to delay or ration treatments.
"Patients are started on a therapy and they may go through
four or five or six cycles. When a drug becomes short, your
cycle may be coming up a month later than planned," he said.
"Oncologists, especially in major cancer centers, are in a
quandary. 'Do I start my patient on therapy? Do I save what I
have for patients who started two cycles ago?'"
Dr. Richard Schilsky, cancer specialist at the University
of Chicago and a past ASCO president, said the shortages have
been going on for about nine months with no sign of abating.
"When you talk to the drug companies, they say there are
manufacturing problems or they are taking plants offline and
then it takes a while to get them back up," he said.
"They point the finger at the FDA (Food and Drug
Administration), saying the FDA is under-resourced and they
can't get plants inspected to allow resumption of drug
production. The drug suppliers are in the middle of this as
well," he said.
But underlying all of this, he said, is a dearth of
financial incentive to make the lower-cost cancer drugs,
especially when new cancer drugs command huge premium prices.
"The return on investment of manufacturing generic drugs is
pretty low. If something goes wrong, it may be that some
manufacturers decide to pull out rather than fix the problem."
Hospira spokesman Dan Rosenberg said shortages arise for
many reasons -- capacity constraints, commodity shortfalls, or
when a competitor withdraws its product for some reason or when
competitors have shortfalls. It is not always possible for
Hospira to ramp up production that quickly, Rosenberg said.
"We are doing everything we can to ensure access to these
products for clinicians and patients," he said. "Often, we
continue manufacturing products at a loss because we realize
there is a critical medical need and we are the only company
that provides the medication."
A Teva spokesman said its California plant that makes
injectable drugs, which was closed last year due to quality
issues, is now back up. But the plant will not reach full
capacity until the end of this year.
To address the shortages, U.S. senators Amy Klobuchar, a
Democrat from Minnesota, and Robert Casey, a Democrat from
Pennsylvania, introduced a bill in February that would make
drug companies inform the FDA about supply problems or plans to
stop making a drug. The FDA would then have time to work with
other suppliers to make the drugs or arrange for imports.
"That is a canary in the coal mine," Schilsky said. "It
doesn't really resolve the fundamental problem."
(Reporting by Debra Sherman and Julie Steenhuysen; Editing by
Michele Gershberg and Matthew Lewis)