http://www.usatoday.com/story/news/nation/2013/06/03/drug-shortages-cancer-patients/2382597/

Most cancer specialists say their patients have been affected by shortages of critical cancer drugs, mostly caused by manufacturing problems at pharmaceutical plants.

Shortages of critical cancer drugs are threatening the care of patients who are already fighting for their lives, a new study shows.
About 83% of cancer specialists reported a drug shortage in the past six months, and 92% said patients' care has been affected, according to a survey of 245 doctors to be presented Monday in Chicago at the annual meeting of the American Society of Clinical Oncology.
According to the new survey, 38% of doctors switched from a generic to a more expensive, name-brand drug, a practice that can vastly increase the cost of treatment, according to the study, co-authored by Keerthi Gogineni at the University of Pennsylvania School of Medicine.
The oral drug capecitabine, for example, costs 140 times as much as a generic intravenous drug, 5-FU, which is the backbone of chemotherapy regimens for many gastrointestinal tumors.
There were 251 drug shortages of all kinds in 2011 and 121 in 2012, according to the Food and Drug Administration.
In February, the University of Utah Drug Information Service, which closely tracks shortages, reported national and regional shortages of 320 drugs, the highest since 2010.
The survey of cancer specialists who couldn't provide the most appropriate drug — at any price — said they were forced to make painful choices:
• 79% switched chemotherapy regimens, which may be less effective.
• 43% delayed treatment, which can give cancers more time to spread.
• 37% chose among patients, leaving some patients to go without a critical medication.
• 29% omitted doses, which can reduce the chance of controlling cancer.
• 20% reduced doses, which also may harm a patient's chances of surviving.
• 17% sent patients to other doctors.
Some hospitals hold the equivalent of lotteries to decide which patients get a drug, says cancer researcher William Li, executive director of the Angiogenesis Foundation, which sponsors research of blood vessel growth.
Chemotherapy regimens have been carefully studied in clinical trials to give patients the highest chance of survival and lowest risk of serious side effects, Gogineni says.
In many cases, doctor's don't know how disrupting these meticulously planned regimens will affect a patient's health. "There is a lot of improvisation when trying to make educated guesses about what is the safest alternative," Gogineni says. At her hospital, "we were upfront with everybody about the fact that we might need to make a modification."
A December study from St. Jude Children's Research Hospital linked drug shortages to higher relapse rates among young people with Hodgkin lymphoma enrolled in a national clinical trial. The number of patients who were cancer free after two years fell from 88% before the shortage to 75% after the shortage when doctors had to substitute an alternate drug.
While none of the children and young adults in the trial died, those who relapsed will need additional intensive therapies — including high-dose chemo and a bone-marrow transplant — that increase their risk of infertility and other health problems in the future.
In a March survey from St. Jude, 16% of hospital pharmacists and others said drug shortages have caused patients' cancers to get worse, treatment-related complications or other problems. One hospital blamed a patient death on a drug shortage.
All fields of medicine have been hit by drug shortages, which have limited supplies of everything from ADHD medications to painkillers.
Cancer patients have been hit especially hard, however, because many of the shortages involve sterile injectable drugs, which are commonly used in oncology, Gogineni says.
Shortages of intravenous vitamins also have affected cancer patients, who often have special nutritional needs.
And although shortages aren't a new problem, 70% of doctors said their hospitals or practices had no formal guidelines about how to allocate scarce drugs, the survey found.
About two-thirds of drug shortages in recent years were related to quality problems that led manufacturers to stop production, said Margaret Hamburg, commissioner of the Food and Drug Administration, in an April interview with USA TODAY's editorial board.
Some of the "very real" quality concerns have included rubber fragments, glass shards or microbial contamination in liquid medications, Hamburg said.
"Most of these are made at facilities that are very old," she said.
Because older generic drugs are less profitable than newer, branded ones, there may be only one or two companies still making them, Gogineni says. If one manufacturer shuts down, that leaves a huge void.
She says she's concerned about manufacturers prioritizing the most profitable drugs, rather than the most life-saving.
"Some manufacturers have diverted existing production capacity from less profitable agents to more expensive agents," Gogineni says.
Since 2012, manufacturers have been required to alert the FDA of impending shortages. That can give the FDA time to approve drugs from a different manufacturer or allow importation from overseas.
The FDA used these methods to avert 280 drug shortages last year, Hamburg says.
While doctors have praised the FDA's efforts, some say more needs to be done.
"It baffles the mind that this is happening in a modern society," Li says.
Chemotherapy drugs most commonly reported to be in short supply, according to a survey of 245 oncologists:
1. Leucovorin, 68% (used to treat colorectal cancer).
2. Liposomal doxorubicin, 63% (used in ovarian cancer, multiple myeloma, others).
3. 5-FU, 19% (used in many gastrointestinal cancers).
4. Bleomycin,18% (used in testicular cancer, Hodgkin lymphoma and others).
5. Cytarabine, 7% (used to treat acute myeloid leukemia, non-Hodgkin lymphoma, others).