Mairéad McInerney will never know if modifications to her treatment plan diminished her chances of surviving stage 3 triple-negative breast cancer. Critical drug shortages have compelled her to change course not once but twice.
Taxol (paclitaxel), one of the two drugs she was due to take, was unavailable the first time around, according to McInerney, who was diagnosed in December 2022. She explained that McInerney began the other two chemotherapeutic agents (Adriamycin and Cytoxan) in the regimen first, which was not the standard treatment approach.
The second time, after McInerney concluded the Adriamycin-Cytoxan infusions, she was to begin 12 weeks of Taxol combined with carboplatin. Taxol was restocked at the Abramson Cancer Centre of Penn Medicine in Philadelphia, where McInerney is receiving treatment. However, carboplatin was only accessible during the first ten weeks of the 12-week protocol.
For McInerney, who has one of the most aggressive forms of breast cancer, the alterations felt like a series of emotional blows.
McInerney, a 38-year-old Philadelphia suburb-dwelling healthcare executive, said, “You navigate so much and engage in all these mental gymnastics to wrap your head around enduring your infusions and your treatments.” “And then to hear that something is unavailable is yet another gut punch because you are still powerless.”
In recent weeks, cancer physician groups have become increasingly vocal about national shortages of essential medications, including long-standing generics such as carboplatin and cisplatin. According to the National Comprehensive Cancer Network, a nonprofit alliance of academic cancer centers, these medicines form the backbone of potentially curative treatments for breast, lung, prostate, and gynecologic cancers, as well as several types of leukemia and lymphoma.
According to a survey conducted by the National Comprehensive Cancer Network in late May, nearly all cancer centers—93%—have reported a carboplatin shortage, and 70% have cisplatin supply problems. Medical organizations have issued guidelines for rationing the existing supply.
The Society of Gynecologic Oncology, for instance, has issued a series of statements, including one on May 24 recommending that platinum drugs be “prioritized for curative intent or in settings where prolonged clinical benefit is anticipated.”
The deficits force patients and physicians to make difficult decisions amidst the already overwhelming stress of a cancer diagnosis. McInerney recalled asking her doctor if there was a suitable replacement for the two missing carboplatin doses, to which he responded that there was none.
In other circumstances, cancer physicians say, a patient may receive an alternative drug, but one that is not the standard drug of choice or that may have more adverse effects. Or patients may have to travel further to obtain the necessary medications.
“We are all at the end of our rope,” said Brian Orr, a gynecologic oncologist at the Hollings Cancer Centre at the Medical University of South Carolina in Charleston.
According to Orr, the platinum drugs carboplatin and cisplatin offer the greatest chance of curing patients with cervical, ovarian, uterine, and other gynecologic cancers. Outside of a select few [treatment] advancements, platinum has been the most significant addition to our cancer care in terms of survival, according to Orr. Therefore, it is essential.
Orr explained that clinicians at Hollings Cancer Centre began rationing platinum drugs shortly before the Society of Gynecologic Oncology issued its recommendations. According to him, as of the end of June, the dose for each carboplatin infusion had been reduced marginally, but patients were still receiving the recommended total number of treatments.
Regarding the availability of carboplatin, Orr stated, “We may have only a few weeks’ worth of stock left before we run out.” As a result, an influx of new patients have been traveling an hour and a half from Beaufort, South Carolina, to Hollings Cancer Centre to receive chemotherapy, as local practices have run out of carboplatin or cisplatin, he said.
In recent weeks, California oncologist Ravi Rao estimated that only one-third of his chemotherapy-bound patients could receive cisplatin or carboplatin on any given day. “If we run out today and someone comes in tomorrow for treatment, if we don’t have the drug, we just don’t give it,” said Rao, a member of a large practice in Fresno and board member of the Community Oncology Alliance, a non-profit organization that represents community oncologists.
In certain instances, such as for a protocol used with breast cancer patients, Rao has altered the order of infusion medications, beginning the portion containing a platinum drug later in the sequence in the hope that it will be available by then. If platinum pharmaceuticals are out of stock, there are viable alternatives for other patients, such as those with lung cancer, he said.
Rao, describing a recent decision involving a 79-year-old man with stage 2 bladder cancer, stated that there are instances when there are no viable alternatives. The individual, who has been undergoing radiation therapy, was also scheduled to receive carboplatin and Taxol. However, the more efficacious of the two drugs, carboplatin, was unavailable for three of the six recommended cycles of chemotherapy.
For the fourth cycle, Rao prescribed mitomycin, a treatment for bladder cancer that is typically avoided in elderly patients because it is a “difficult drug” with a greater likelihood of severe side effects, such as vomiting and diarrhea. If the pharmacological treatment is unsuccessful, the man’s bladder will likely be removed, he said.
“I told him, ‘I’ve never given it to someone at age 79. But I’ll give you some,'” Rao stated. “I decreased the dosage and am keeping my fingers crossed. I would be horrified if he went through the entirety of his treatment without receiving a single dose of efficacious chemotherapy.”
Andrew Shuman, a cancer surgeon and medical ethicist at the University of Michigan, stated that cancer physicians may be required to make these types of drug charges on brief notice, with limited information about when a drug will be unavailable and when it will be restocked.
“The vast majority of cancer treatments are based on high-quality evidence from clinical trials,” testified Shuman before a congressional committee in March regarding drug shortages. And drug shortages force us to make decisions that are not based on evidence because we are simply doing the best we can, which is an extremely uncomfortable position for cancer physicians to be in.
In the meantime, patients like Molly Young read the news, tally their pills, and attempt to remain calm. Young had only six doses of the targeted therapy Tukysa (tucatinib), which she takes twice daily as part of a multidrug regimen for stage 4 breast cancer, remaining at the end of June. At her previous two appointments at Walter Reed National Military Medical Centre in Bethesda, Maryland, the medication was unavailable.
Young ultimately obtained more drugs before she ran out. Nevertheless, the 36-year-old singer and voice/piano instructor stated that uncertainty can be unbearable at times.
“You worry even if you have all of your medications,” she said. “Will they function? Am I enduring pain for a reason? Is this truly going to save my life? So the added anxiety of “Do I even have these poisonous medications that are so difficult to take and so difficult to handle?”
Emotions spanning from anger and fear to a sense of being overwhelmed and possibly anxiety or depression can make living with cancer psychologically challenging. In a 2018 study of 3,724 adult patients, 50 percent reported elevated psychological distress. This anxiety was associated with physical issues, including fatigue and sleep disturbances.
Rao is especially concerned about ovarian cancer patients, as research indicates that platinum-based medications increase the likelihood of a cure. Each year, nearly 20,000 women are diagnosed with ovarian cancer; roughly half of them will survive for at least another five years. Rao stated that, for patients with advanced cancer, missing even one platinum dose “will have an effect on the cure rate. However, I cannot tell you how much.”
Although cisplatin and carboplatin are equally effective against ovarian cancer, Dr. Rao prefers carboplatin because it is less likely to cause nausea, fatigue, and other adverse effects. When Christina Castro-Garcia first met with Dr. Rao earlier this year after being diagnosed with stage 3 ovarian cancer, he assured her that the prescribed regimen of carboplatin and Taxol would result in relatively mild adverse effects.
During her first cycle of chemotherapy, she received both medications and felt mostly exhausted and slightly nauseous. During the second cycle, however, only Taxol was accessible. For the subsequent two regimens, carboplatin was unavailable, so Castro-Garcia received cisplatin and Taxol instead. She experienced the increased side effects immediately.
Last month, the 44-year-old woman described her sluggish recuperation from the most recent cycle: “This last time, I was probably sick for a full day.” “Basically, I was vomiting for three days. But for an entire day, I couldn’t even keep water down.”
Castro-Garcia attributes her ability to deal with drug shortages and illness to her husband’s support and her religious beliefs. She added, “It feels like you’re literally walking in the dark, never knowing what the day will bring.”
McInerney, who is clinically trained as a social worker, stated that she has witnessed the emotional impact of these shortages on her cancer care team, whom she lauds for working tirelessly on behalf of patients. McInerney questioned what happens to cancer patients in more rural areas of the country if large institutions such as the University of Pennsylvania struggle to obtain enough of these medicines.
When McInerney inquired about the impact of the two missed dosages of carboplatin, her cancer care team stated that they believed she had received sufficient chemotherapy.
“But I’m still angry,” she said. “I will admit that if I experience a recurrence in the future, this will be in the back of my mind. Is it because I began in such a manner because Taxol was unavailable? Is it because I did not receive the final, comprehensive protocol for those two treatments?”