Patient Adherence, a Challenge of Oral Chemotherapy

• An extended series of visits to a treatment center,
• Where the patient would be hooked up to an IV, often for hours, and infused with a heavy dose of anticancer drugs and supportive care medicines,
• All while being constantly monitored by healthcare professionals.

Nowadays, that same process often can be accomplished by simply sending the patient home with a bottle of pills.

That’s because advances in oral chemotherapy are radically changing the way doctors, pharmacists, and their patients manage cancer.

Jim Schwartz, RPh, a registered pharmacist for nearly 4 decades, has witnessed this sea change in treatment firsthand.

“Twenty-five years ago there were 8 oral drugs, and they were all oral forms of intravenous drugs,” says Schwartz, executive director of pharmacy operations at Texas Oncology.

Treatment options began to change radically after the Human Genome Project was completed in 2003. The research, which identified the genes and sequencing of human DNA, allowed researchers to determine genetic alterations in many types of cancers, and create tailor-made drugs to treat them.

“Right now there are probably 75 or 80 oral drugs, including the original 8,” Schwartz says. “These new drugs are specifically designed as orals without intravenous equivalents.”

Many of the new pharmaceuticals are a far cry from older infusion therapies, which often took a “shotgun” approach to treatment, killing both cancerous and non-cancerous cells, a strategy that led to a host of adverse effects, including hair loss, low white blood cell counts, and leukemia.

“The new oral drugs are specially designed for specific cancer markers,” Schwartz explains. “They target specific receptors and work like a lock-and-key mechanism with specific cells to prevent the cancer from duplicating.”

The list of oral oncolytics continues to expand each year, with a half dozen or more new drugs being introduced annually.

“It’s really exploded over the last 5 to 7 years,” notes Nancy Egerton, area manager of pharmacy services for New York Oncology Hematology.

The Challenge of Adherence

But for all its promise, oral therapy introduces a new variable: patient adherence. Because unlike traditional infusion oncology—where doctors, nurses and pharmacists directly oversee the process—oral chemotherapy requires the patients themselves to correctly administer the drug.

“These drugs are very toxic, with a lot of side effects and dosed accordingly with scheduled breaks,” Egerton says. “So the regimen is essential.”

But following the proper regimen—taking the correct dose at the correct time in the correct manner—is sometimes easier said than done. Scheduling alone can present a challenge.

Some drugs, such as lenalidomide (Revlimid), which is used to treat multiple myeloma, follow a relatively simple regimen: 2 or 3 weeks on, followed by a week of rest.

Others have much more complicated schedules. TAS-102 (Lonsurf), an oral chemotherapy for colon cancer, is taken twice a day for 5 days, followed by 2 days of rest for 2 weeks,

followed by another 2 full weeks of rest before the entire process starts over again. And dosages sometimes require a combination of pills, depending on the patient’s weight.

“When it first came to market, it was like ‘you gotta be kidding me, how complex can it get?’” Egerton recalls. “So it’s really critical that someone is keeping up with patients and

making sure they take their drugs.”

Adherence is a multi-faceted issue. Is the patient following instructions? Is the drug being stored correctly? Is the patient spreading out doses to make the prescription last longer? Is the patient cutting back on doses due to side effects?

“With intravenous treatment we have direct control,” says Jan Merriman, RPh, BCOP, director of clinical and pharmacy services for Minnesota Oncology. “We set up the appointment, we put the drug into them and we know that the dose is correct.

“With oral chemotherapy, the process is no longer under our direct control. When the patients are taking the drug at home, we never really know if they are taking it correctly.”

Patients in the United States don’t have a great track record when it comes to taking any long-term medication. Overall adherence estimates range from 17% to 80%, with an average of around 50%, according to several studies. Adherence rates for oral cancer drugs are little better.

Writing in theJournal of Hematology Oncology Pharmacy, Lea Ann Hansen, PharmD, BCOP, notes the “common assumption that adherence to oral anticancer agents would be higher, due to the severity of the disease, has been proven untrue. Studies indicate the adherence rates for cancer therapy are 15% to 97%.”

The ramifications for patients with cancer not properly following their regimens can be severe, warns Egerton. Non-adherence can lead to disease progression, additional physician visits, longer hospital stays, and increased mortality.

“Compliance in this country is terrible to begin with,” she says. “But with cancer, compliance becomes absolutely critical.”

Factors Driving Non-Adherence

Yet, even with their health or sometimes their very lives at stake, some patients with cancer still won’t take their medicine. Why? Oncology pharmacists blame this therapeutic failure on a number of factors, including:

Adverse effects:As with any medicine, anticancer drugs can have a number of immediate and long-term adverse effects. Chemotherapy can cause fatigue, decreased blood cell counts, neuropathy, mouth sores, and other complications.

Schwartz notes that orals tend to have different adverse effects than transfusion drugs, including more dermatological reactions, as well as kidney and liver complications. “A lot of times patients won’t tell you they’re having side effects,” he says. “They’ll just quit taking the drug.”

Adherence issues with everolimus (Afinitor), for instance, have been well documented. The drug, which was created to treat renal cancer but is now used mostly for long-term treatment of breast cancer, can cause mouth sores. They’re usually mild, but are still one reason why patients discontinue therapy.

And then there’s nausea. Along with fatigue, it’s one of the most common adverse effects of any chemotherapy, and one that can be proactively managed in a clinical setting.

But outside of the clinic, it’s another matter entirely, notes Egerton.

“Sometimes people don’t take their medicines because they’re at home and they don’t feel well,” she says. “If you’re nauseous, the last thing you want to do is take a pill.”

Confusion:While coping with any illness can be an unsettling, receiving a cancer diagnosis is particularly devastating. In addition to comprehending what’s wrong with them, patients also must struggle with treatment decisions, insurance issues, lifestyle changes and financial concerns.

It’s a lot to take in all at once.

“Sometimes patients [with cancer] are so overwhelmed with things going on that it’s hard for them to absorb anything else,” Egerton says.

And dealing with the insurance bureaucracy often only adds to the confusion.

Merriman, who oversees pharmacy operations at 12 Minnesota clinics, has seen some patients quickly become frustrated by this “whole new world” of paperwork and phone calls.

“We’re talking about people that are sick who just don’t have the energy to deal with this,” she says. “Some can’t wade through all the red tape and just give up.”

Cost:Cancer treatment—whether it includes infusion or oral regimens, surgery, radiation, or other therapies—is an expensive proposition. Insurance and financial concerns can be overwhelming for some patients.

The popular leukemia drug imatinib (Gleevec), for example, currently costs about $350 per dose, according to the independent pharmaceutical data website Drugs.com. everolimus runs $518 per dose, while one capsule of lenalidomide, the multiple myeloma drug, costs $726.

How much each patient will actually end up spending on these drugs is dictated by their insurance plan’s co-pay structure and out-of-pocket limits.

Medicare patients, however, face a particular challenge. Unlike transfusion therapy, which is covered under Part B as a medically necessary service, oral treatment falls under Part D as a prescription drug expense. As such, it requires patients to first cover the Medicare donut hole—currently $3750—followed by a 10% copay for each subsequent prescription.

With monthly drug costs running in excess of $10,000 on many oral oncolytics, this can be a daunting proposition. And the cost can lead some patients to make ill-advised decisions, according to Egerton.

“Nobody wants to pay for these drugs because they are so expensive,” she says. “Because of the expense, they may decide to take one pill every other day or every third, or even cut the pills in half. And most of these pills should never be cut in half.”

The National Community Oncology Dispensing Association (NCODA)is the first grassroots, not-for-profit organization founded to strengthen oncology organizations with medically integrated dispensing (MID) services. NCODA’s “Going Beyond the First Fill” strategy utilizes quality standards and continuity of care benchmarks through its patient-centered initiatives and partnerships. For more information, go towww.ncoda.org.

Bill Wimbiscus, a contributor for NCODA, is a Chicago-area journalist with more than 35 years’ experience. He has written and edited for numerous newspapers and magazines.

Reference:

Impact of Nonadherence to Cancer Therapy. Journal of Hematology Oncology Pharmacy website.jhoponline.com/component/mams/?view=article&artid=14873:top-14873&secid=11003:top-sec-11003&catid.