A Scary Shortage Of A Colon Cancer Drug
11 CommentsBy Ed Silverman // December 17th, 2008 // 8:41 am
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, according to Forbes.
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, 5-flurouracil. A drug cocktail of 5FU and leucovorin is now a backbone of colon cancer chemo, the mag writes. 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 and Bedford Labs, a subsidiary of Boehringer Ingelheim. In November, the FDA said both drugmakers were unable to make an adequate supply, but hard info about the shortage has been difficult to obtain, beyond what is posted on the FDA Web site.
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,” Kate Murphy, director of research communication for the Colorectal Cancer Coalition, a patient advocacy group, tells Forbes. 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, according to Murphy. “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,” an FDA spokeswoman tells Forbes. “Bedford and Teva are both releasing product currently, and we are continuing to monitor this situation.”
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,” Forbes writes. 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,” a spokeswoman tells the mag. “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 leucovorin, according to Forbes.
“We’ve been fielding phone calls from institutions that are running out,” 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, tells the mag. “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 today to try to figure out how to handle ongoing clinical trials if more leucovorin does not emerge, Forbes reports. 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 Avastin.
“This is starting to be an issue nationally,” Leonard Saltz, a leading colon cancer doctor and researcher at Memorial Sloan-Kettering Cancer Center in New York, tells Forbes. He warns 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,” Michael Katz, a cancer survivor who is chair of a committee of patients that advises ECOG, tells Forbes. He worries 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 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. “How many drugs are out there that are just being produced by the grace of God?”
Dan A.
http://en.wikipedia.org/wiki/Folinic_acid
Interesting supplement….
Welcome To The Future
Too many post’ers on this site seem to relish in the demise of the pharma industry.
Welcome to the future.
It turns out that our nation actually needs a pharma industry. Lack of new and innovative medicines reaching patients in-need. Lack of existing medicines, once generic, from being made available in necessary quantities.
Good luck to us all “re-importing” our way out of these (and plenty of other) future crises.
Condor
Hey “Welcome” — this is the case of a little boy crying wolf.
The shortage of this one drug is lamentable, but it is no more evidence of a VAST a pardigm-shift, than the suggestion made, by PhRMA — last week, in trupeted press-releases — that Pharma is now *closely-allied* with the new, incoming Administration on how to improve access for all Americans.
It. is. simply. not. true. at. all.
[PhRMA is all about getting "theirs" -- FIRST!]
Said in a more cryptic form, “the singular form of the word ‘data’ — is ‘anecdote’. . .”
Cheers!
Condor
Perhaps I should have been clearer, above — to blame this shortage — on generic-drugs’ availabilty, generally — is a classic non-sequitur.
To REALLY ensure supplies, price supports (yes, EVEN FOR GNERICS!) would be needed (if we are to follow the logic, such as it is, here)– NOT some goofy return to OVER-priced branded compounds — with endless exclusivity periods.
Namaste.
Salmon
I just read in the Washington Post that we shouldn’t worry about the automobile industry disappearing because we still have a lot of US based manufacturing and exporting, especially pharmaceuticals.
Even if we do allow preemption etc. these companies are still outsourcing manufacturing to India and China (along with R&D). Preemption won’t change that.
Plus if preemption passes it’s the taxpayers who are stuck with the bills for paying for the health care of all the people being maimed.
I certainly want a strong and vigorous US pharmaceutical industry, however I don’t want the US to be left with a mess and the bill with almost nothing in return.
Nathan
Condor writes: “I just read in the Washington Post that we shouldn’t worry about the automobile industry disappearing because we still have a lot of US based manufacturing and exporting, especially pharmaceuticals.”
I guess the writers at the Washington post haven’t been reading this website. BMS is getting rid of 20% of staff. Wyeth chopped 10%. Merck 10%. Pfizer - who knows - at least 10%. Those layoffs don’t include the “shift” of resources from US sites to sites in India/China. I believe that at last count Ed’s running total was in the range of 80,000 jobs being lost in the pharma industry over the last year or so. (note that the entire “big-three” in Detroit employ about 200,000)
I certainly do not consider pharma to be the “bright spot” of the American economy.
Nathan
Woops - that was Salmon, not Condor, who wrote the above Washington Post quote.
Philip Rudnick
“A Scary Shortage of A Colon Cancer Drug”?
If people’s lives were not at stake, I’d say,”Don’t make me laugh.” Like all other cancer patients, the lives of colon cancer patients are *totally* in the hands of their oncologists, and that is what oncologists want and insist on. They want their patients to be totally dependent on them. Specifically, they warn their patients not to “stray”, i.e.,not to be taken in by nutritional “quacks” and “quackery”. They say this even though
they are almost completely ignorant of the vast, documented, scientific literature on nutraceuticals vs. cancer.
The comments below are addressed to colon cancer patients, but similar information is available for cancer patients in general.
If you want to exercise a modicum of intellectual independence and control over your life:
The non-inclusive list below is one of nutraceuticals which have been documented in the medical literature to have anti-colon-cancer activity. You can verify this statement by first going to the link to the National Library of Medicine, or Medline,
http://gateway.nlm.nih.gov/gw/Cmd
and in the “Search” box, entering in (two examples):
“colon cancer ellagic acid” or
“colon cancer Vitamin D”, etc. (Leave out the quotation marks.)
A partial list of safe, non-prescription, readily-avaialable anti-colon-cancer nutraceuticals:
propolis
quercetin (in onions, apples…)
ginger
phytic acid (in grains)
CLA (or conjugated linoleic acid)
aged garlic extract (or AGE)
green tea
EGCG (in green tea)
ellagic acid (in berries)
Vitamin D
folic acid
tart cherries
flaxseed lignans
grape seed (available as a powder)
lycopene (in cooked tomatoes)
tocotrienols (in wheat germ)
N-butyrate
berberine
L-carnitine
I3C and its metabolite DIM (in broccoli)
gamma tocopherol(in NATURAL Vitamin E)
lutein
MSM (methyl sulfonyl methane)
omega-3 fatty acids (in fish oil)
rice bran (stabilized only)
milk thistle
turmeric and curcumin
cranberries
phaseolus (mung beans)
cocoa
resveratrol
black raspberries
selenium
Vitamin B6
I’m a retired chemistry professor and have no commercial interest in any of these nutraceuticals. You are welcome to contact me at pbrudnick@yahoo.com
Philip Rudnick
Anne M
This is a pretty sick thing to even think that this drug so highly depended upon is not available….and you don’t even know when it will be or get a straight answer. With the cancer rate so high and what cancer patients have to go through just depending on some drug or doctor to keep them alive on a daily basis. How terrible. It is all amount the bottom line not the lives of these poor people just trying to live day to day and survive this alful dreaded disease.
Greg Pawelski
Leucovorin is a faster acting and more potent form of folic acid, used as a rescue after dose-intense 5FU therapy to lessen and counteract the effect of 5FU toxicity and other folic acid antagonists. Patients are given resuce drugs for any incident in which the use of a medication may have harmed the patient. Cancer sufferers are taking doses of potentially toxic treatments that are possibly well in excess of what they need. Many cancer drugs may be just as effective and produce fewer side effects if taken over shorter periods and in lower doses.
Government auditors found some years ago that the price of Leucovorin calcium listed for $18.44. Medicare paid 95%, or $17.52, but some physicians bought it for $2.77. Marketing the Spread occurs when a drug maker uses the differences between the price paid for a drug by public health care programs and the actual cost of the drug charged to doctors as a tool for selling products. The GAO reported that the 86% Spread for Leucovorin meant that a Medicare beneficiary’s co-pay alone would actually be more than the physician paid for the drug.
Xeloda (capecitabine) offers fewer side-effects and 85% less time with the doctor or at the hospital. Again, would a clinical trial to show when drugs are selected with and without the presence of profit differential, clinical outcomes would be the same? Most oncologists use injectable treatment because they are more profitable than oral therapies, and remains an important source of income for their practices. Is this better for the patient?
Xeloda is proving much more convenient, has fewer side effects, and has shown it is giving colon cancer patients a better chance of surviving the disease. Yes, Xeloda is more expensive than Leucovorin, but Leucovorin can more renumerative for the oncologist.
Mrs Cancer
My spouse is a recent colon cancer dx. He began his postsurgical chemo last friday 1/23/09. I knew he would be on a 3 drug cocktail incl leucovorin as this is common protocol for his stage of disease. When they handed us phamplets on only 2 drugs, I didnt think much about it until I read about the FDA shortage of leucovorin - which kind of makes sense now. I dont really appreciate the oncologists not sharing this critical missing information with us, and just assumed we’re regular dummies who dont know nothing unless we’re told. Everyone deserves to be fully aware of outcomes that affect our lives directly, and withholding drug shortage info from us ‘poor cancer’ patients just perpetuates the myth that we’re expendable and you dont care enough to have the honor of having doctor in front of your name.