Two of the most widely used cancer drugs are in short supply amid one of the worst chemotherapy shortages in decades, forcing clinics across the U.S. to ration the lifesaving medicines.
Centers are altering treatment regimens, restricting the therapies to the cases most likely to be cured or sending patients to hospitals with greater access to the drugs.
“We have changed regimens for hundreds of patients so far because we can’t get the drugs,” said Lucio Gordan, president and managing physician of Florida Cancer Specialists & Research Institute, which operates 90 clinics across the state. “In 21 years in oncology, I’ve never had to do this before.”
The mess highlights the fragility of a U.S. pharmaceutical supply chain that stretches around the world and remains under stress since periodic outages began over a decade ago. Overall drug shortages have soared to a five-year peak as low profit margins discourage investment in generic manufacturing, allowing small disruptions to become dangerously magnified. While oncologists devise workarounds, the White House has formed a task force focused on the issue and committees in the U.S. House and Senate are investigating.
In a May survey of some of the nation’s biggest oncology centers, 93% reported shortages of the cancer drug carboplatin, while 70% reported shortages of related cisplatin. Nine centers reported lacking sufficient carboplatin to treat all patients according to plan.
The crunch began when an Intas Pharmaceuticals Ltd. plant in Ahmedabad, India, that makes generic cancer drugs for the U.S. stopped manufacturing. The halt followed an FDA inspection late last year that found numerous problems, including a truckload of shredded quality-control documents and a worker pouring acid on test results.
Intas said it prioritizes safety and efficacy and that it voluntarily stopped making and distributing products from the facility after the FDA report. The company said it’s “implementing remediation measures” and working on a plan to resume production, but declined to provide a timeline for when this would happen. It was allowed to ship some drugs after enhanced quality checks, but said late Wednesday that it no longer has any cisplatin inventory.
Half of the U.S.’s cisplatin and 20% of its carboplatin come from Intas, said Erin Fox, director of the University of Utah’s drug information service that tracks shortages. The cancer drugs cost less than $50 a vial compared with thousands of dollars for doses of newer, advanced immunotherapies.
The price far underestimates their value: Cisplatin, first sold in the U.S. in 1978, is so widely used it’s sometimes called the penicillin of cancer drugs. It’s irreplaceable for treating some bladder tumors and can cure some testicular cancers.
Women have been particularly impacted as carboplatin is “the No. 1 agent” against many ovarian and endometrial cancers, and cisplatin is a key drug for certain cervical cancers, said Jennifer Rubatt, a gynecologic oncologist in the Denver area. In April, she began making drug substitutions and sending some patients to other institutions with better supply.
As news of cisplatin shortages spread and hospitals tried to stock up on the drug, orders spiked early this year, according to Premier, which helps about half of U.S. health systems buy medicines. The four other cisplatin manufacturers couldn’t keep up with demand, according to the U.S. Food and Drug Administration.
From February to May, hospitals ordered twice the normal amount of cisplatin but received less than half the regular supply, Premier’s data show. That was followed by a shortage of carboplatin, which is sometimes used as a substitute.
Centers of all sizes are affected, but community oncology practices like Florida Cancer Specialists appear to be the worst hit. Even after cutting the size of carboplatin doses in April to preserve supply, the chain ran out entirely for 12 days the next month, forcing many patients to be switched to other drugs.
Jennifer Bradley, 49, started a regimen including carboplatin after being diagnosed with tumors in both breasts in January. When she came in for a scheduled treatment at Florida Cancer Specialists in May, carboplatin wasn’t available. While she responded well to treatment without some doses, she worries it will leave her more vulnerable to a recurrence.
“You don’t anticipate that in America you are not going to be able to get the drugs you need for your full treatment program,” she said.
The chain has carboplatin back in stock and received a shipment of cisplatin Wednesday, said Gordan, the president.
The University of Wisconsin’s cancer center rationed carboplatin for two weeks through early June. Patients with potentially curable tumors received preference over those with advanced cases where the goal was merely slowing the disease, said Lee Wilke, senior medical director of clinical cancer services at UW Health, the university’s health system.
“It was one of the hardest decisions to make,” Wilke said. “These are life-prolonging and lifesaving drugs.”
The center now has enough carboplatin to avoid rationing, but it is still lowering doses, Wilke said. And questions persist about switching drugs in the middle of treatment – data are almost nonexistent, said Utah’s Fox.
Other manufacturers are trying to ease the shortage: Pfizer upped carboplatin production to seven days a week from five, and Fresenius is making more cisplatin and carboplatin, although at the expense of other products. The American Society of Clinical Oncology published guidelines for treating gastrointestinal and breast cancers without the drugs.
Meanwhile, the FDA began allowing China’s Qilu Pharmaceutical to sell a version of cisplatin in the U.S. – even though the agency hasn’t approved it. The FDA is permitting imports of unapproved versions of two other chemotherapy drugs, fludarabine and streptozocin, because of shortages.
A solution to the longterm problem – low prices that give drugmakers little incentive to produce excess supply – remains out of sight.
“The problem is basic economics,” said Ted Okon, executive director of the Community Oncology Alliance, a Washington lobbying group for cancer clinics. “We are not going to fix this until we have a dose of reality about the financial issues here.”
(c) 2023, Bloomberg · Robert Langreth, Ike Swetlitz
Source: Matzav
