Chemotherapy drug shortages leave medical experts scrambling

NEW YORK, June 19 (UPI) -- Unprecedented shortages of key cancer drugs in the United States could disrupt treatment for tens of thousands of patients with various forms of the disease in coming months, experts told UPI.

With more than 10 drugs used for chemotherapy in treating cancer among the dozens considered to be in short supply by the Food and Drug Administration, hospitals have been forced to find new suppliers or adjust patient doses to limit disruptions in life-saving care, the experts said.

"Current shortages of cancer drugs are impacting clinical practice for all health systems across the United States," Jeffrey Pilz, assistant director of pharmacy, medication safety and drug policy for the Ohio State University Comprehensive Cancer Center in Columbus, told UPI in an email.

"The severity and duration of the shortages has been unprecedented, with even large cancer centers having to use down most of their inventory," he said.

The shortages have forced cancer centers to adjust doses of chemotherapy drugs, identify new suppliers and distributors and use other treatments, Pilz said.

Earlier this month, the FDA authorized temporary importation of an unapproved chemotherapy drug from China to ease shortages in supplies of cisplatin.

The drug is used in a variety of cancers, including testicular cancer, ovarian cancer, cervical cancer, bladder cancer, lung cancer and brain tumors.

"Thankfully, our [centers] have been able to maintain patients on treatments thus far," Pilz said.

"However, as many chemotherapy agents age and fewer companies produce them, there is a real concern for the long-term outlook in obtaining the preferred drugs for patients for healthcare in general," he said.

Remnant of COVID-19

The FDA attributes current drug shortages to disruptions in the supply chain caused by the COVID-19 pandemic. These disruptions have affected the availability of pharmaceutical ingredients and components, as well as "finished dose forms," the agency said.

However, drug shortages "are not a new issue" in the United States and have occurred previously because many products are produced, experts said.

"Dramatic shortages have periodically impacted healthcare for the last decade, even for critical and essential medications like chemotherapy," Pilz said.

Still, "these ongoing cancer shortages are a unique and troubling concern," he said.

That's because many of them impact drugs used to treat blood and bone marrow cancers, according to Dr. Leo I Gordon, co-director of the Hematologic Malignancies Program at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago.

In addition to cisplatin, among the drugs used in cancer patients considered to be in short supply recently include azacytidine, which is used to treat bone marrow cancers as well as some forms of leukemia, or blood cancers, according to the FDA.

Other drugs used to treat leukemia and non-Hodgkin's lymphoma, another blood cancer, such as cytarabine and fludarabine, also have been on the agency's shortage list.

Similarly, dacarbazine, a drug used to treat Hodgkin's disease, another form of lymphoma, has experienced shortages recently, according to the agency.

Collectively, about 60,000 people in the United States will be diagnosed with these cancers this year, the National Cancer Institute said.

"Multiple clinical service lines across oncology are being affected by shortages at the moment," Nicole Soriano, a hematology and oncology clinical pharmacist at Northwestern Memorial Hospital in Chicago, told UPI in an email.

"In particular, we have been affected by the dacarbazine and fludarabine shortages," she said.

Other chemotherapy agents in short supply include carboplatin, which is used to treat ovarian cancer, and lutetium Lu 177/vipivotide tetraxetan, a drug marketed as Pluvicto used to treat some forms of prostate cancer.

Since receiving FDA approval for the drug in April, Novartis has been "ramping up" production at its New Jersey facility, with plans to "continue to increase" capacity "through the year helping to ensure stable, reliable supply," according to a statement from the company's media relations department.

The company also is expanding its manufacturing network in both the United States and globally, including a new facility in Indianapolis expected to open "as soon as the end of this year," it said.

In addition to chemotherapy drugs, several products administered to cancer patients to manage the side effects associated with treatment have experienced supply chain issues.

These include amifostine, which manages kidney damage caused by chemotherapy; indigotindisulfonate sodium, a contrast dye marketed as Indigo Carmine and used in CT scans and magnetic resonance imaging; and dexamethasone, given to cancer patients to prevent allergic reactions to treatment and nausea and vomiting, a common side effect.

"It is concerning to both our providers and institution as a whole that these shortages keep occurring and pose a threat to patient care," Soriano said.

"Patients should be able to receive curative therapy at the appropriate doses without having to worry about shortages impacting their ability to properly treat their cancer," she said.

Dealing with the dilemma

In response to these shortages, cancer centers nationally have taken steps to identify new suppliers and ration treatments to maintain supplies, experts told UPI.

This has led to an increase in the use of generic forms of chemotherapy drugs, some of which also are experiencing shortages, according to the FDA.

Some cancer centers have also been forced to switch patients to older, potentially less effective chemotherapy drugs that are less affected by shortages, Ohio State's Pilz said.

In addition, "some institutions have implemented actions like rationing of available inventory, which may cause interruption or delay in patient treatment," he said.

As part of a rationing approach that has a basis in science, a technique called "dose rounding," clinicians take a patient's prescribed dose of chemotherapy -- usually determined by body weight -- and adjust it down to the nearest vial size, according to the National Comprehensive Cancer Network.

Dose rounding is typically used to reduce drug waste, and usually is limited to within 5% or 10% of the prescribed amount, the alliance of 33 cancer centers said.

The approach doesn't appear to impact the effectiveness of chemotherapy in the short-term, but few studies have assessed its clinical impact, experts said.

For some, treatments have not been impacted.

"Our patients have not experienced [treatment] interruptions," Kate Berlin, a hematology and oncology clinical pharmacist at Northwestern Memorial Hospital, told UPI in an email.

However, "we are aware that the shortages are disrupting treatment across the country, resulting in absent or insufficient doses for patients including at community oncology centers," she said.

In recent months, the Ohio State University Comprehensive Cancer Center, which includes the James Cancer Hospital, also in Columbus, has seen increases in the number of patients referred to it from smaller cancer centers in the region, according to Pilz.

This is because these smaller health systems have fewer resources to combat the effects of shortages, he said.

Increased "importation of foreign, unapproved drug products" like the Chinese-manufactured cisplatin also is an option, Pilz said.

However, this is not a straightforward process, because "it is only viable if sufficient product exists overseas, which is not always the case due to the global impact of modern shortages," he said.

The FDA considers safety and "any differences between the imported and U.S.-approved medications" in making its recommendations, he added.

Still, in the case of cisplatin, the imported version has labeling in Chinese only, meaning distributors have to relabel products to ensure proper dosing, according to Pilz.

"As a clinician, it is more concerning to run out of product entirely than using an imported item, knowing that the FDA is still vetting the import source and product," Pilz said.

"There are operational challenges that make this less than ideal -- it is really a Band-Aid to the larger systemic issues driving shortages," he said.