Several widely used branded and generic cancer drugs are in short supply, causing some people to be treated with less-effective medications or even die while waiting for the medication to become available.
Pluvicto, used to treat advanced prostate cancer, and injectable methotrexate, cisplatin, and fluorouracil — chemotherapy drugs that target many different cancers — are all becoming scarce, according to the U.S. Food and Drug Administration (FDA). A fifth drug, BCG, used to treat bladder cancer, is also dwindling, according to the University of Minnesota.
A delay in cancer treatment of even just a few weeks can affect a person's survival. A study published in the November 2020 BMJ found that every month of delayed treatment was associated with a 10 percent increased risk of death.
“Drug shortages have been a major challenge for the last decade, especially in acute-care hospitals,” says Jeffrey Pilz, PharmD, an assistant director of pharmacy, medication safety, and drug policy for the Ohio State University Wexner Medical Center and the James Cancer Hospital and Solove Research Institute in Columbus.
Recent disruption in global supply chains and production issues have combined to create shortages for a greater number of drugs, longer-lasting shortages, and less product availability during a shortage, says Dr. Pilz.
“Current drug shortages also are impacting ever more important medications, not just older generics that are no longer first-line therapies. For 2023, the number of drug shortages is forecast to reach a record number,” says Pilz.
At a minimum, drug shortages are a frustrating and inconvenient experience for patients, says Pilz. “At their worst, drug shortages historically have been deadly for patients,” he says.
What Cancer Drugs Are Affected by Shortages and Why?
There are currently five drugs used in cancer treatment that are running low. Shortage severity varies by institution and region, adds Pilz.
Pluvicto (injectable lutetium vipivotide tetraxetan) This medication is used to improve survival time in people with advanced prostate cancer. In a pivotal study announced in December 2022, men who received the drug lived a median of 15 months, which is 4 months longer than the median for patients who didn’t get the drug.
Pluvicto is currently made in just a single factory in Italy, notes Pilz. “Because it is a radiopharmaceutical [a drug that contains a radioactive substance], it can only be produced in small batches within a few days of when it needs to be delivered to patients. Any interruption in production or delivery may delay doses,” he says.
Although Novartis is running the factory at full capacity, the high demand for this agent and previous delivery interruptions have led to a backlog in production and the resulting shortage, says Pilz.
There is a prioritization program for patients who have already received at least one dose so that they can complete the course of therapy, according to the company. Long term, there are plans to increase production of the drug with two new manufacturing sites in the United States.
Meanwhile, these delays have had tragic consequences for some cancer patients. At Dana-Farber Cancer Institute in Boston, delays to starting treatment on Pluvicto went from 41 days in May 2022 to three months by October. During that period, 127 patients were approved for the drug and 6 died waiting, according to a report from the Wall Street Journal.
Bacillus Calmette-Guerin (BCG) BCG is considered an “essential drug” in the treatment of bladder cancer, according to the University of Minnesota. The drug has been in shortage since 2019.
Because this drug, too, has only one manufacturer and is produced in only one facility, an increased global demand has led to a prolonged shortage, says Pilz. “Plans are underway to open at least one new facility, but this will take several years before authorized,” says Pilz.
In the United States alone, the shortage has caused more than 8,000 people with moderate to advanced bladder cancer to receive less-than-optimal care, according to the End Drug Shortages Alliance (EDSA).
Injectable cisplatin, methotrexate, and fluorouracil These generic drugs are widely used to treat common cancers in adults and children.
Methotrexate treats acute lymphoblastic leukemia in children and a number of cancers in adults, including breast, head and neck, lung, bone, and uterine cancers. The drug has been scarce since March 14, according to the American Society of Health System Pharmacists (ASHP).
Supplies of cisplatin, used to treat metastatic ovarian and bladder cancer, have been tight since March 6, per ASHP.
The fluorouracil shortage was first reported on March 14, according to ASHP. The injectable drug is used to treat colon, breast, pancreas, and stomach cancer.
Manufacturing Issues Create Shortages
Unfortunately, drug shortages are not a new problem, says William Dahut, MD, the chief scientific officer at the American Cancer Society. “Shortages tend to occur with drugs that are no longer on patent and are made by only one or two manufacturers,” he says.
The factories that manufacture generic drugs are often old, and if there’s a problem at the primary site of production, the impact can be significant. “Since production sites are limited, there are no options to easily make up the deficits,” says Dr. Dahut.
From the perspective of frontline clinicians, it can be hard to determine the specific causes of individual drug shortages, says Pilz. “There is a lack of transparency with the pharmaceutical industry as to causes of drug shortages, timeline to resolution, and even where products are made. Some manufacturers may volunteer this detail when known, but it is not required outside of the mandatory reporting elements to the FDA,” he says.
Ultimately, inexpensive (less than $9 a dose) medications that are only available as generics provide little financial incentive for manufacturers to reinvest in the production line or expand production capability, says Pilz.
Even though they are commonly used, many of the traditional chemotherapy agents fall in this category, he says.
“However, shortages may still impact newer, branded medications such as Pluvicto due to production issues,” says Pilz.
More Transparency Would Minimize the Impact of Shortages on Patients
Although there has been more attention focused on shortages lately, Pilz believes there needs to be significant investment by the pharmaceutical industry, significant regulatory changes, or both to find meaningful solutions to the underlying problems.
“The lack of transparency in the manufacturing and supply chain for pharmaceuticals is one area where change could be implemented relatively quickly,” he says.
If manufacturers provided information on issues with specific production sites, the amount of medication available, and a timeline for getting back up to speed after a production problem, that would allow healthcare providers to make better plans to mitigate shortages and minimize patient impact, he says.
What to Do if You or a Loved One Is Affected by a Drug Shortage
It’s reasonable to check in with your healthcare team about possible shortages before starting treatment, says Dahut. “If this is a concern, discuss potential alternatives with them. If a shortage occurs during therapy, ask about alternative routes of administration [oral versus IV], similar drugs in the class of agents, or potentially different therapeutic strategies,” he suggests.
“If you are struggling to find an outpatient prescription product, ask your provider or pharmacist if there are other locations where the product may be available or if there is a reasonable alternative therapy,” says Pilz.