Tony Shepard learned this spring that he had vocal cord cancer, but was encouraged when his doctor said he had an 88 percent chance of being cured with chemotherapy and radiation.
That outlook has begun to deteriorate in recent weeks, however, after the oncology practice he attends in Central California began sporadically running out of the critical medication he needs.
Since Mr. Shepard’s doctor informed him of the deficiency, each treatment session has felt like a game of “Russian roulette,” he said, knowing that failure would mean the removal of his vocal cords and the disappearance of his voice.
“I try not to even think about it,” says 62-year-old Mr. Shepard, a gas station manager in Madera, a city in California’s Central Valley. “It’s a scary thing that you don’t really want to think about — but you know it’s a reality.”
The country’s months-long shortage of highly potent cancer drugs continues, forcing patients and their doctors to face an even grimmer reality than that cancer typically presents. Thousands of patients like Mr. Shepard face heartbreaking options, treatment delays and a potentially bleak future.
Oncologists are concerned that the alternatives to two crucial chemotherapy drugs are much less effective at treating certain cancers, and are sometimes even more toxic. The backup therapies, or lack thereof, pose a particularly troubling outlook for patients with ovarian, testicular, breast, lung, and head and neck cancers, they say.
There are few, if any, signs that the deficit will diminish any time soon. A factory that was a major producer of the more popular drugs shut down late last year and has not reopened, depleting supplies. The easing of restrictions on medicines imported from China this month has provided some relief, but doctors said the influx has not yet made a major dent. Some companies that sell the drugs predict the shortage will continue into the fall or beyond.
So far, neither a group of experts organized by the Biden administration nor prominent medical organizations have found a way to avoid rationing the crucial chemo drugs.
To bridge the gaps, some doctors are extending care intervals and skimming precious milliliters to stretch doses. Others are turning to a strategy of surgery first and chemo later, counting on a resumption of supplies.
One of the nation’s top cancer care groups, the American Society of Clinical Oncology, is now advising doctors with small amounts of the drugs to administer them to patients with a chance of a cure — and to withhold them from patients with recurrent or widespread disease .
“We’re in a situation where patients are left to fend for themselves, and we’re really concerned that survival could be compromised by the lack of chemotherapy,” says Dr. Angeles Alvarez Secord, president of the Society of Gynecologic Oncology and professor at Duke University School of Medicine.
Two major chemotherapy drugs, cisplatin and carboplatin, are being deployed as first-line drugs in cocktails used to shrink or eliminate tumors. More than a dozen cancer drugs are also officially in short supply, as are hundreds of other drugs, including antibiotics and sterile injectable fluids. Still, doctors predict that the absence of the powerful chemotherapy will harm patients the most.
Cisplatin and carboplatin are cheap: They cost $15 and $23 per vial, according to the US Pharmacopeia, a nonprofit organization focused on medication safety and supply. But manufacturing the drugs requires a reliable supply of platinum, a metal used, as well as a sterile factory and special controls to protect workers from the drugs’ toxic effects. As a result, few companies make them.
The most recent shortages of these commonly used drugs occurred when a leading manufacturer, Intas Pharmaceuticals, halted production in December after the Food and Drug Administration conducted a surprise inspection of its facility in Ahmedabad, India. The U.S. agency released a report saying workers were acid shredding, ripping and pouring on quality control records and noted a “cascade of failures” at the site.
The company’s subsidiary, Accord Healthcare, in Durham, North Carolina, recently said it was still making factory improvements needed to restart production.
This spring, the effects of the closure of Intas were deeply felt. A National Comprehensive Cancer Network survey of academic treatment centers published earlier this month found that 93 percent of the 27 centers that responded were deficient in carboplatin. As a result, 36 percent of them reported changing treatments for their patients, resorting to lower doses and longer intervals between therapies.
At the cCare Cancer Center in Fresno, California, where Mr. Shepard receives care for his vocal cord cancer, efforts to stretch supply have given way to sporadic availability. For the past six weeks, vials of the platinum drugs have been unavailable about half the time, said an oncologist, Dr. Ravi Rao.
He said Mr. Shepard’s chance of being cured without the drugs would drop from about 90 percent to about 45 percent. Fortunately, Mr. Shepard said, the drugs are available for the first two of seven treatments.
Ovarian cancer patients face the worst outlook, said Dr. Rao, because of how common the disease is and how central platinum drugs have been in tackling it for decades. Without those drugs, a patient with extensive ovarian cancer has a survival rate of about 30 percent, he said.
“This shortage will lead to people’s deaths,” said Dr. Rao, who is also a board member of the Community Oncology Alliance. “There’s just no escaping it. You cannot remove these life-saving drugs and not have bad results.
Others facing increased threats are testicular cancer patients, as cisplatin has a known record of curing even advanced cases, said Dr. Julie Gralow, the ASCO chief medical officer, in her testimony before a House subcommittee earlier this month.
“This is critical and may affect as many as half a million Americans with just these two drugs,” said Dr. Gralow.
For Florida Cancer Specialists, with more than 90 locations, the shortfall initially meant retaining 10 to 15 percent of a patient’s dose to stretch supplies, said Dr. Lucio Gordan, president of the practice.
That wasn’t enough, so doctors started giving the drugs only to patients with a chance of a cure or to patients participating in clinical trials. The practice found some products at wildly inflated prices – apparent price gouging – but bought them anyway.
Still, practice in May was 12 days without carboplatin and eight days without cisplatin, said Dr. Gordon.
Arias Pitts, 33, who was diagnosed with aggressive breast cancer in April, hit the shortfall when she arrived May 16 to begin treatment. The carboplatin her doctor had ordered for the first of six rounds of chemotherapy was not available.
“Of course I had questions and concerns,” said Ms. Pitts, an academic advisor at the University of South Florida and a single mother of a 4-year-old. She added, “It’s stressful.”
The FDA has taken steps to reduce the shortfall. It oversaw the testing and release of batches of the platinum drugs made by Intas in India before the shutdown, but that supply has now been depleted.
It also temporarily allows China-based Qilu Pharmaceuticals to ship its cisplatin to the United States.
Jordan Berman, a vice president of Apotex Pharmaceuticals, a Toronto-based company that imports the Qilu drugs, said it received shipments of cisplatin on June 6 and began routing them through major U.S. distributors.
Oncologists and supply chain experts said there was so far little data to measure the effect of the imports. About 600 vials of cisplatin from China arrived at Florida Cancer Specialists earlier this month, said Dr. Gordon. But that wasn’t enough for the practice to offer the drugs back to patients with advanced or recurrent cancers.
“It’s about six days of treatment for us,” said Dr. Gordon. “We’re messing around.”
Studies in the 1980s and 1990s showed that the platinum drugs were a vast improvement over existing treatments, performed best when combined with other drugs, and doubled response rates for ovarian and head and neck cancers. The platinum drugs pushed the five-year survival rate for testicular cancer to 95 percent from about 10 percent.
While newer immunotherapy treatments have improved outcomes for patients with certain types of cancer, such as melanoma, oncologists are also incorporating them into cocktails with the platinum drugs to prolong their lives and increase survival potential.
“Overall, we haven’t seen these cancer home runs in recent years,” said Dr. Mikkael Sekeres, a University of Miami oncologist and former FDA oncology advisor.
Oncologists advising the field amid the current shortages have urged those treating early stage lung cancer patients to send them to a center that has the drugs, noting “there are no equally effective alternatives.”
Dr. Evan Myers, a researcher at Duke University in the department of obstetrics and gynecology, said he planned to measure the effects of the shortages. A study of another drug deficiency in children and adolescents with Hodgkin lymphoma found that the replacement drug was “significantly less effective” and reduced the survival rate for the young people who received the backup treatment.
Dr. Myers said this year’s shortfalls would at least likely have an effect on the quality of life of people undergoing treatment. “They’ll wait for the other shoe to drop,” he said.
Doctors also struggle to deliver such devastating news, said Dr. Prasanthi Ganesa, medical director of the Center for Cancer and Blood Disorders in Fort Worth. Her practice looks at each case individually, but also prioritizes critical doses for patients with potential cures.
“I can imagine a patient listening to this and saying, ‘You know, I’m trying to live longer, that’s my priority. So I need that medicine, doctor,” she said. “We feel really powerless.”
The situation requires action, said Dr. Karen Knudsen, executive director of the American Cancer Society. The White House and Congress, which have discussed the problem, have put forward few concrete solutions.
“The need for a lasting solution is growing day by day,” said Dr. Knudsen, adding, “Patients stick around.”
