June 23, 2011 -- A shortage of Taxol, an intravenous chemotherapy workhorse for ovarian, breast, lung and colon cancers, demonstrates once again how vulnerable U.S. hospitals and clinics are to an increasingly unreliable pharmaceutical supply chain, leaving patients at risk.
Paclitaxel, the generic version of Taxol, joins 196 other drugs on a shortage list compiled by the American Society of Health-System Pharmacists in Bethesda, Md.
Although no one has been able to quantify the number of lives jeopardized by the shortages, the lengthy list underscores that the country is in the midst of a "public health crisis of drugs overall," said Cynthia Reilly, director of the group's practice development division.
Paclitaxel made the list May 13, with a June 16 update. Additions in the last month include such chemotherapy mainstays as doxorubicin, daunorubicin, carboplatin, vincristine and cytarabine; the quick-acting anesthetic propofol; the injectable painkiller Fentanyl and injectable forms of several powerful antibiotics: clindamycin, ciprofloxacin and gentamicin.
For more than a year, "we've been having a crescendoing of drugs that are in short supply. This has been going on for some time now," said Dr. Michael P. Link, a Stanford University pediatric oncologist who serves as president of the American Society of Clinical Oncology. He called the paclitaxel crunch "another add-on."
Although some drug shortages can be eased with simple substitutions, regimens that use paclitaxel often lack equally effective substitutes. "That's what makes not just this, but all of the chemotherapy shortages significant," Reilly said. "There's cancer patients who will die because of this. This could change their survival."
Some chemotherapy shortages have been making it harder to treat certain malignancies, Link said. "Without cytarabine and daunorubicin, you cannot treat leukemia," he said.
At Stanford's Lucile Packard Children's Hospital, where he practices, the daunorubicin shortage means "we are at risk for having to triage our patients; which patients we'll be able to give the drugs to. We're hoping to get more so we don't face that awful crisis. Other practices have."
Shelly Burgess, a spokeswoman for the Food and Drug Administration, said the paclitaxel shortage was "not a complete national outage" because most of the five generic manufacturers still had some of the drug on hand. Bedford Laboratories of Bedford, Ohio, had paclitaxel on back order and "plans to have supplies available again by the end of the month," she said.
Bedford, which has 20 percent of the market for three doses of the drug, expects to release paclitaxel vials into the marketplace soon, said spokesman Jason Kurtz. The company's backlog increased the pressure on the other manufacturers to expedite production.
Teva Pharmaceuticals USA, based in North Wales, Pa., anticipates "some constraint through the summer," said spokeswoman Denise Bradley.
Dan Rosenberg, a spokesman for Hospira of Lake Forest, Ill., said he didn't "have a time frame" for when Hospira could deliver more medication to the marketplace, but it was working to help fill the supply gap.
Debra Lynn Ross, a spokeswoman for APP Pharmaceuticals of Schaumburg, Ill., did not provide an immediate response to questions about the shortage.
Shortages Disproportionately Affect Smaller Hospitals
Stanford's Link described the shortages of paclitaxel as geographically variable and partly dependent on the size and clout of institutions. "Large institutions have multiple suppliers, multiple distributors to work with," he said. "They're likely to have more leverage and more options in terms of getting in a supply of drugs."
But most adult cancer patients in the United States are treated in smaller practices in their communities, he said, which "tend to operate more on an order-as-needed basis." With less leverage and fewer alternate suppliers, he said, "they're really getting killed."
The American Society of Clinical Oncology has been collecting anecdotes to get a feel for some of the impact. "We've heard horror stories where patients have actually gone to another state to get their own supply of the drug," he said.
In response to an ABC News request for comment about their paclitaxel supplies, a dozen major U.S. hospitals and medical centers said they hadn't experienced a shortage. Among them: the Fred Hutchinson Cancer Research Center in Seattle; Duke University in Durham, N.C., the University of Rochester Medical Center in New York; the University of Michigan Comprehensive Cancer Center in Ann Arbor; Maimonides Cancer Center in Brooklyn, N.Y.; Georgetown University's Lombardi Comprehensive Cancer Center in Washington, D.C. and Indiana University-Purdue University in Indianapolis.
Still, some of the largest and most renowned U.S. medical centers reported being short of paclitaxel, along with other important drugs. "In my 25 years as a cancer MD, I have never, never seen this," said Dr. Jay Brooks, chairman of hematology-oncology at the Ochsner Clinic Foundation and Hospital in New Orleans, where 800 doctors and 20 oncologists "work together to shift drugs where needed for patients."
At the University of Medicine and Dentistry of New Jersey, where paclitaxel is "our No. 1 drug," some paclitaxel has been stashed away "and we are continually ordering from various sources to try to maintain a continual supply," said Dr. Lillian Pliner, acting director of hematology/oncology. If the drug becomes unavailable, "we would have to look at alternate treatment protocols."
Dr. Roy B. Jones, professor of medicine at the MD Anderson Cancer Center in Houston, called the shortage "manageable but worrisome," and said his medical center was handling it "with fingers crossed." He said he was aware of "many" chemotherapy drugs in short supply, including four at critically low levels and another 20 that he considered "worrisome."
Beaumont Hospital in Royal Oak, Mich., is paying 3.5 times its usual contract cost for paclitaxel to make sure patient care isn't interrupted, Annette Karageanes, assistant director of its pharmacy supply chain, said Thursday. Paclitaxel was "one of 40 products that we evaluated this morning during our drug shortage meeting," she said.
Some Big Medical Centers Managing for Now
Three other large, academic medical centers reported being aware of the paclitaxel shortage but managing to mitigate any effect on cancer patients. Dr. Julian Schink, chief of gynecologic oncology at Northwestern University in Chicago, where ovarian cancer patients receive paclitaxel plus either carboplatin or cisplatin, said his pharmacy "pro-actively identified this issue and stocked up" on Teva's paclitaxel.
Dr. James Speyer, medical director of the NYU Clinical Cancer Center, said NYU worked with several suppliers "so that we have not had to delay treatment of patients." And pharmacist Anita A. Garcia, interim director of investigational drugs at the Cancer Therapy and Research Center at the University of Texas Health Sciences Center in San Antonio, said the center's distributors "are rationing the use of the drug."
Burgeoning drug shortages in the past decade, particularly among injectable generics, suggest that the U.S. pharmaceutical business is operating under "an economic model that apparently is no longer tenable," said Dr. Neal J. Meropol, chief of hematology and oncology at University Hospitals Case Medical Center in Cleveland.
He suggested the system might need to change if producers cannot make adequate profits on low-cost generic drugs "to make it worthwhile to continue producing them with a high degree of reliability."