The medical community increasingly recognizes that many patients aren’t perfect pill-takers. And the solution may be as simple as improving communication. “When I formulate the treatment plan, I really involve the patient,” says Lidia Schapira, an oncologist at Massachusetts General Hospital in Boston. “I ask the patient to let me know of any reluctance or hesitation or concerns, and we talk about them.”

To make adherence easier, patients may want to discuss questions such as these with their medical team:

Is there anything special to do before the prescription is filled? Are there forms to fill out? Authorizations to request from an insurance provider? Do only specific pharmacies carry the medication? If the medication is ordered online, does it need special handling in the mail? Is cost an issue?

What if the patient has trouble swallowing pills?

Uneasy swallowers might assume they can crush an oral anticancer therapy pill. “It’s never a good idea to crush a pill unless that’s been studied,” says Donna Berry, a nurse scientist at the Dana-Farber Cancer Institute in Boston. The patient might inhale dust from chemotherapy agents or damage the time-release mechanism.

If the obstacle is the pill’s size, the doctor might be able to reformulate the prescription so several small pills equal one big one. Techniques that kids use for pills come in handy. “You’re going to laugh at this,” Berry says, “but put the pill in pudding or ice cream, so it slides down easy.”

Some patients may not have realized how difficult it would be to swallow the pill. At Dana-Farber, a nurse calls a patient 72 hours after the regimen begins to determine, among other things, whether the pill is easy to take—and if not, if there might be other options.

How can patients remember to take the pill?

The idea of a daily chemotherapy pill “has to be something that sticks in your head,” says medical researcher Joyce Cramer, formerly of Yale University. “And only you can put [that idea] there.” Patients should tell themselves that every day, for the next 30 or 60 or 90 days, or perhaps the indefinite future if they have metastatic disease, they must take a pill. In studies, Cramer has found the power of a mental bookmark really works, creating “a lingering feeling that you’re supposed to be doing something.” Then they need to connect that thought to their daily habits.

I have made it part of my nighttime regimen: Wash your face, brush your teeth, take your pill. I picked a time when I knew I wouldn’t forget it, and it’s worked for me.

The doctor or pharmacist should state how and when the pill should be taken, says Frank Federico, a registered pharmacist and executive director at the nonprofit Institute for Healthcare Improvement in Cambridge, Mass. Then the patient should be asked to explain his or her personal plan: “I’ll take the pill every night at 10 p.m., as part of my getting-ready-for-bed routine.” That’s what works for Barbara Errickson, 64, of Brigantine, N.J., who takes a daily dose of Tarceva (erlotinib) for stage 4 lung cancer. “I have made it part of my nighttime regimen: Wash your face, brush your teeth, take your pill. I picked a time when I knew I wouldn’t forget it, and it’s worked for me.”

What if patients are still afraid they’ll forget?

Then they’ll need to set up reminders. Philippe Johnson, 33, was prescribed etoposide to fight his stage 2b testicular cancer in 2007. The meds had to be refrigerated, thus, the South Carolina resident kept the pill container in the fridge’s butter drawer, so it stared him in the face every morning when he went for the milk.

Lillian Shockney, a registered nurse and administrative director of the Johns Hopkins Avon Foundation Breast Center in Baltimore—and a two-time breast cancer survivor&mdash;is also a refrigerator advocate. For her own meds, she puts a note on the refrigerator door: “Don’t forget to take your pills.”

But even a refrigerator note may eventually become like wallpaper. For patients who need a daily jolt, calendars and electronic reminders are an option.

That’s a question patients should ask when they get the prescription.

“Find out upfront whether you should try to make it up,” Berry says. The answer may be that a double dose is too much. “But that’s something that needs to be individualized per patient.”

Doctors should tell patients what to expect—and patients should tell their doctor what they experience (keeping a log helps), so management strategies can be found. Otherwise, side effects might make patients want to stop taking the pill.

Articles

Features

To improve adherence, patients with cancer must recognize barriers.

Overcoming Obstacles to Cancer Medication Adherence

With the growing complexities of taking oral anticancer therapies—multiple medications, complicated dosing schedules and various side effects&mdash;it can be challenging to remember to take a pill on time, much less the correct manner in which to do so. There are many different methods available for keeping track of oral medications, but finding what works best for an individual patient is most important.

The Health Belief Model, which was developed by public health experts, essentially helps patients weigh the risks and benefits of a health decision, in this case, taking an oral anticancer medication. With this model, patients have to believe a few simple concepts in order to take action (and to take their medicine): they have to believe that the illness is serious and they are vulnerable to it, realize that taking action will help, feel they can follow through, understand the barriers to completing the task and have strategies for completing the action. For example, a full compartment in a pillbox can be a reminder to take the medicine, while an empty one is reassurance they’ve followed through.

Another technique is called compliance therapy and comes from the field of psychiatry to help patients continue with their anti-psychotic medication. The basis of this technique is self-reflection, with the idea being that critical thinking can help improve an individual’s motivation. Patients are asked open-ended questions to help them better articulate for themselves why and how they should keep up with their medicines.

When first handed a prescription, patients need to make sure they understand what it says and what it means going forward. If they don’t understand, they should feel free to ask their doctor or nurse questions (see list). They should also find out who they should be in contact with if they have questions once they start taking the drug. Some doctors’ offices might have a system in place for automatic reminders, or may provide telephone support or can have other tools, education materials and tips to offer.

There are plenty of apps for smartphones and other devices that can be used as alarms or reminders. In June 2007, the Food and Drug Administration approved the Electronic Medication Management Assistant (EMMA), which stores and dispenses medication and lets doctors monitor their patients’ day-to-day well-being, including allowing doctors to adjust doses and medication times.

Support groups can sometimes provide the best advice—from someone who’s been there. These groups can be a source of practical tips on taking pills and managing side effects, as well as providing recommendations for resources that might be able to help with other issues, such as treatment costs. Patients can also enlist the help of family and friends who can help out with reminder phone calls or by learning about the prescription.

Research has shown that a crucial component in taking medications correctly and on time is communicating with the healthcare team. Here are some questions patients and caregivers can ask the healthcare team when a new prescription is issued:

> What is the name of the medication (both trade and generic)?

> What condition is it supposed to treat?

> Who should be called if there are side effects?

> What foods or drugs could interact with this medication?

> When will this prescription need to be refilled?

Practical ideas for improving adherence and essential questions to ask the healthcare team.

Quick Tips for Medication Adherence

As more patients with cancer embrace the convenience and control offered by oral anticancer therapies, they also face the daunting task of policing themselves when it comes to taking their medicine. Many aren’t doing a good job, which can lead to potentially harmful consequences.

“There’s been a seismic shift in the way we treat cancer over the last several years,” says Ellen Stovall, senior health policy advisor for the National Coalition for Cancer Survivorship. “And adherence has become a serious issue.”

There is no consensus in the healthcare industry on exactly how adherence to medication is defined. The term “compliance” has given way in recent years to “adherence,” a less judgmental term that refers to how consistently a patient takes a medication exactly as prescribed. In a 2003 report, the World Health Organization defined adherence to longterm therapy as “the extent to which a person’s behavior—taking medication, following a diet,and/or executing lifestyle changes, corresponds with agreed recommendations from a healthcare provider.”

Before the rise in oral anticancer therapy—any cancer medication in liquid, tablet or capsule form that is taken by mouth&mdash;cancer treatment was typically administered on-site at hospitals and clinics, where patients were closely monitored by doctors and nurses who could actually see patients receive their treatment, such as through intravenous (I.V.) infusion, and adherence was assured. Today, though, many cancer patients take their oral anticancer therapy at home, shifting the burden of adherence to patients and their families.

‘‘The thought was that cancer patients in general adhere better to their medication because of the implications of not doing so, but that’s not actually the case.’’

And, as it turns out, many patients are not doing that. Studies show that adherence rates for oral anticancer therapies are as low as 16 percent and as high as 100 percent, indicating we really don’t have a clear picture of the adherence issue. Cancer patients are like many other patients taking oral medications, especially for chronic conditions that often require long-term treatment, such as diabetes and high blood pressure, where nonadherence rates average about 50 percent. The challenge of nonadherence is expected to increase in coming years with the rise in chronic health conditions, increased long-term maintenance therapy for cancer and the growth in oral anticancer therapies—about 25 percent of cancer medications in development are oral formulations, with more than a dozen already on the market. Also, with more supportive medications for symptoms, bone health and other chronic conditions, the sheer number of pills a patient requires creates more chance of missing doses.

“The thought was that cancer patients in general adhere better to their medication because of the implications of not doing so, but that’s not actually the case,” says Robin Sommers, a nurse practitioner in the Center for Gastrointestinal Oncology at the Dana-Farber Cancer Institute in Boston. “Even when faced with lifethreatening disease, a patient’s adherence can fall short.”

The consequences of not adhering to medication exactly as prescribed are numerous and potentially harmful. It’s estimated that nonadherence across all health conditions causes 125,000 deaths annually in the U. S. and generates as much as $300 billion in healthcare costs. In cancer patients, poor adherence may be associated with disease progression and resistance to the medication. It also can lead to medical complications, more frequent doctor visits and more frequent and longer hospitalizations. Even some participants in clinical trials are nonadherent, which can lead to inaccurate information about medication safety and efficacy.

Nonadherence is typically traced to any of five interrelated factors: the healthcare system, socio-economic factors, patient behavior, treatment-related factors and disease-related factors. Some patients, for example, can’t afford their medication, so they don’t get refills. Others have trouble understanding the directions or have difficulty in swallowing pills.

Nonadherence doesn’t simply mean forgetting a dose; it occurs in many ways. Some patients may forget to take several doses because they’re traveling or they feel well and cancer is no longer at the forefront of every thought. Nonadherence also occurs when a patient doesn’t take the medication at the right time of day or with the appropriate foods. And, because serious side effects, such as frequent diarrhea, can affect how much of a medication the body absorbs, patients are considered nonadherent when they fail to report these side effects to their healthcare team. At the other end of the spectrum, some patients are nonadherent because they arbitrarily double up on doses, believing it will give them a cancerfighting advantage or because they worry that an oral formulation isn’t as effective.

Leibel Harelik of Austin, Texas, found out about the dangers of nonadherence. Harelik, 63, received a diagnosis of advanced prostate cancer in July 2002 and tried numerous treatments. He had been taking Zytiga (abiraterone acetate) for only a few months when he began experimenting with the dosing of the drug and his other medications in an attempt to reduce the side effects. “I was having such a hard time trying to adapt to the medication,” Harelik says. “So I’d drop a pill, and, instead of taking four a day, I’d take three. And I’d either not take my prednisone, or I’d take half a prednisone. I was trying to manipulate it.” Although he admits to experimenting with the drugs on his own, he says he told his doctors what he was doing.

The results were disastrous. Harelik wound up hospitalized with life-threatening health problems and later needed rehabilitation to regain strength. “It was a newer medication, and no one knew much about it,” he says. Harelik doesn’t blame his doctors for what happened. “They were doing their best to appease me and help me. I don’t think I would manipulate my medications any more. I learned my lesson the hard way.”

In some cases though, it’s doctors who aren’t following recommended prescribing guidelines. This so-called off-label prescribing practice leads to inadvertent nonadherence. This is a problem in treating chronic myeloid leukemia (CML), says Greg Stephens, executive director of the National CML Society in Birmingham, Ala.

“We hear about patients, even today, who are on unsupported dosing regimens, having been told to take their therapy drug every other day or to skip a day periodically,” he says. As a result, he continues, “They’re perhaps getting a suboptimal dose, and over time that has proven to be detrimental.”

Numerous methods to improve adherence have been tried. Alarm clocks, talking pill bottles, reminder phone calls and emails, diaries, online patient portals, even web chats—all have been tried with varying levels of success. And yes, there’s even an app for that.

Adherence problems so troubled healthcare workers at Rex Hematology Oncology Associates in Raleigh, N.C., that they developed an oral chemotherapy nurse position to specifically care for patients taking oral anticancer therapies. The program was prompted, in part, because patients were going to their cancer appointments so ill from unreported side effects and other adherence issues that they were sent directly to the hospital, says Mendy Moody, an oncology nurse who initially ran the program and now is manager of Rex Cancer Center of Wakefield in North Carolina. “The goal of the oral chemotherapy program is to help our patients remain safe while taking oral anticancer therapies, and at the same time intervening before the patient becomes so sick that an inpatient hospital admission is needed,” Moody says.

As part of the Rex program, all new patients starting an oral anticancer regimen are given an individual one-hour education session with an oral chemotherapy educator, during which they address potential barriers to adherence and find solutions to increase adherence, such as follow-up phone calls and mandatory appointments before prescription refills. “I think for the most part our patients feel a certain amount of security by doing this,” says Christy Rhodes, an oncology nurse and one of two oral chemotherapy educators at Rex. “We try to make it a good working relationship. I don’t want them hiding side effects from us. And I don’t think anyone has voiced an opinion that they feel overwatched.”

None of the methods to improve adherence have been fail-safe, though, and overall adherence rates to all types of oral medications have changed little in the past few decades. And some experts fear that the problem will only get worse with the growth in oral anticancer therapy and increase in chronic conditions.

“We don’t know what the solutions are,” Stovall says. “Everyone’s talking about the problems right now. But they don’t have a lot of ideas about how to solve the problem. There is no gold standard.”

The National Coalition for Cancer Survivorship is pushing for reforms that it says would improve medication adherence, including working with pharmaceutical companies to develop less toxic medications and oral drug parity in healthcare insurance that would cover costs for healthcare professionals to provide patient education.

I was having such a hard time trying to adapt to the medication. So I’d drop a pill, and, instead of taking four a day, I’d take three.

“We know we need payment reform, delivery reform and regulatory reform, but we don’t have the details on how all these would work,” Stovall says. “Our focus is to identify the policy issues by doing what we do best—bringing stakeholders together to identify causes of nonadherence, to consider policy solutions, and to have coalitions of advocates who are dedicated to implementing the policy issues. It’s irresponsible to put these oral medications out there and not educate patients about adherence.”

As oral chemotherapy becomes more widely used, adherence issues increase.

Troubling Trend: Medication Adherence

As a registered nurse, Jayne Word expected that treatment for her stage 3a breast cancer would be difficult and have many side effects. She had a mastectomy, six rounds of chemotherapy and 33 radiation treatments, and today she is cancer-free.

What she didn’t expect was frustratingly poor communication and very little follow-up education from her oncologist, which caused her to briefly discontinue the tamoxifen she had been prescribed to prevent recurrence.

“I stopped the tamoxifen for two days but felt so guilty knowing [what might happen] if I didn’t take it,” says Word, of Kalamazoo, Mich. “Obtaining my own information and seeing the statistics about the drug’s effectiveness is what kept me [adherent]. I came to accept that [taking the drug] is worth living much longer because of it.”

Word was smart—she quickly realized the potentially dangerous consequences of failing to comply with her drug regimen and restarted her tamoxifen as prescribed. But not all cancer patients are as determined. Every year, researchers report, an untold number stop taking their oral medications or take them only intermittently. Among breast cancer patients taking a hormone therapy, for example, a fourth to about half are nonadherent for the required five years.

Unfortunately, the rate of medication nonadherence among cancer patients is expected to increase as more oral therapies are approved for at-home use. According to a 2010 study published in 

, an estimated 25 percent of cancer chemotherapies will be in oral formulation by 2013.

“Nonadherence is a growing problem,” says Carolyn Blasdel, a family nurse practitioner with the Knight Cancer Institute at Oregon Health and Science University in Portland. “The old paradigm for cancer treatment was a defined, time-limited process, and chemo was given in cycles intravenously. Now, there are many oral medications and the responsibility is completely on the patient to take them or not.”

Blasdel works primarily with patients who have chronic myeloid leukemia (CML), for which oral tyrosine kinase inhibitors (TKIs), such as Gleevec (imatinib) and Tasigna (nilotinib), are often the treatment of choice. She cites a 2009 study published in the journal 

, which concluded that up to a third of the patients in the study taking TKIs could be considered nonadherent, with only 14 percent completely adherent. Another study of CML patients, published in the 

, found that drug adherence tends to decline the longer a treatment progresses.

Nonadherence is a growing problem. Now there are many oral medications and the responsibility is completely on the patient to take them or not.

So why would patients stop taking medications that could save their lives?

“One of the most common reasons in oncology is side effects,” says Ann Partridge, an associate professor of medicine at Harvard Medical School and director of the adult survivorship program at the Dana-Farber Cancer Institute in Boston. “Patients taking a chronic drug to prevent recurrence often don’t feel the gains immediately, and if they have burdensome side effects, they may stop taking it or taking it consistently.”

 Many oral cancer treatments cost more than some patients can afford, even with insurance, due to high co-pays.

 If a patient doesn’t already take a medication every day, remembering to do so can be difficult. “Any kind of behavioral change like that is challenging,” Partridge says.

Some patients worry that the drug isn’t working or won’t actually help.

 “I have patients who say, ‘I don’t like taking drugs because it reminds me of my cancer, so I choose not to,’” Partridge says. “Sometimes they feel it’s not emotionally worth it.”

 Some patients may have difficulty reading labels or understanding dosing directions.

 Some regimens require multiple drugs to be taken at very specific intervals and with or without food.

A secondary issue, Partridge says, is whether patients who may be considered adherent are taking their medications correctly: in the right dose, at the right time and with or without food. All of these factors can change the way a drug is absorbed and how effective it is, Partridge says. “For example, taking a little bit extra may result in significant side effects, including toxicity; while taking half a dose [to make a drug last longer] may be worse than not taking the drug at all.”

“Cancer has a notorious way of becoming resistant to treatment if blood levels of chemotherapy are inadequate,” Blasdel says, “so taking a medication incorrectly can affect a patient’s ability to stay in remission. Once you relapse with CML, for example, it can become very difficult to treat.”

There are a variety of ways to improve adherence among cancer patients, Partridge and Blasdel agree.

Both emphasize the value of open, judgment-free communication between the patient, family, caregivers and treatment team.

“I believe the biggest risk to a patient is not communicating properly with his or her doctor about concerns or difficulties, and the doctor not asking,” Partridge says. “If there are problems, sometimes they can be fixed.”

In many cases, additional solutions may be necessary. If a patient is nonadherent because of difficult side effects, for example, other drugs may be prescribed to control those effects. If money is an issue, the patient’s treatment team may be able to find a drug assistance program or prescribe a less expensive form of treatment.

Patients who have difficulty remembering to take their medications have a number of options available to them, including “reminder apps” (see sidebar) for smartphones and other devices. Pill containers—especially those that electronically remind the patient when to take a medication&mdash;might also boost adherence.

Ultimately it’s the patients’ choice ... But I feel it’s my job as a provider to make sure they are making a well-informed decision on whether to take the pill or not.

“Often helpful to some people is having a partner or spouse remind them, as long as it doesn’t get into nagging,” Blasdel says. “Berating someone is certainly not going to help.”

Improved education can also encourage patients to take their medications as prescribed by helping them understand what their drugs do and the consequences of nonadherence. “The amount of education patients receive can be variable,” Blasdel says. “And even more variable is the amount of information the patient can comprehend and absorb at one time. These people are scared and anxious, and anxiety cuts down on the ability to learn and remember.”

Because of this anxiety, drug education may need to wait until the patient has had sufficient time to come to terms with his or her diagnosis, Blasdel says. It’s also a good idea to bring a family member or friend to take notes and assist with questions.

Ideally, all patients being treated for cancer would take their medications as prescribed. But the reality is quite different: Some patients will be nonadherent despite the efforts of their family and treatment team.

“Ultimately, it’s the patients’ choice—they’re adults,” Partridge says. “But I feel it’s my job as a provider to make sure they are making a well-informed decision on whether to take the pill or not. I’ll work with them to help them if I think that’s the best thing for them.”

Word understands how some cancer patients can fall into nonadherence because she’s been there. Her advice to them is simple: Make sure you feel comfortable with your care provider and don’t hesitate to change providers if communication or education is lacking. “It’s also important that patients ask questions,” she adds. “Among them: What is this medicine for?, What side effects are expected and who do I call about them? and What are my risks if I choose not to take it?”

Patients on anticancer therapies must assume greater responsibility for their treatment.

Taking Charge of Your Cancer Treatment

 magazine tackles a problem that is as old as medicine itself but only recently thrust into the spotlight as a spate of studies gives us a true view of patient adherence to anticancer therapies.

There is no doubt that oral medications have increased in number and effectiveness during the past several decades. Hormone therapy for estrogenpositive breast cancer can cut risk of recurrence by about half and breast cancer death by a third. Why then do up to half of patients not adhere to the five years of therapy that is typically recommended? As you will read in the pages ahead, the reasons are complex and multifaceted. They have to do with medical reasons and side effects, behavioral, social and financial factors—each of these reasons has many subfactors that are not easy to solve, and some are not even well understood. Even with life-saving and nearly curative therapies, such as Gleevec (imatinib) for chronic myeloid leukemia, adherence to medical therapy is problematic.

Creative solutions are being tested and implemented at many cancer centers and practices to improve adherence. These include simple education and awareness. Others involve clever reminders and motivational strategies that can be achieved through the telephone and the Internet. Even high-tech pill dispensers with Wi-Fi connections that can alert the care team to missed doses are being tested and adopted. Newer tests to predict who will get side effects of cancer drugs, and a variety of strategies to minimize these side effects, are also being developed and promise to help with compliance. As the molecular revolution exposes more of cancer’s vulnerabilities, more tumor-specific “druggable” targets will be identified. The next generation of these anticancer therapies is increasingly likely to include orally administered drugs, highlighting the need for more innovation in adherence.

It is difficult to calculate the potential impact of achieving 100 percent adherence to cancer therapies, but every little bit counts. The cancer death rate is now dropping, and these statistics lag behind improvements as a result of new treatments, which suggests that improving adherence can save even more lives. We at 

 hope to do our part by bringing you this special report on medication adherence to inform and continue a dialogue about this problem and to introduce possible solutions. As with many other areas of cancer, this represents a partnership between physicians, patients, researchers, drug companies and the numerous organizations dedicated to improving the outlook for cancer patients.

Professor of Medicine, University of Southern California 

Co-Leader, Women’s Cancer Program at the USC/Norris Comprehensive Cancer Center

Editor's Page

Adherence to oral anticancer medication&mdash;a report card.

Message from the Editor

In many cases, oral anticancer therapies have changed the way cancer is treated. Here’s a look at oral anticancer therapy in three cancer types:

CML is sometimes called the poster child for oral chemotherapy. Prior to May 2001, treatment options of interferon and bone marrow transplantation were suboptimal, with low cure rates and high complication rates. But then a new era in oral anticancer therapy was ushered in when the Food and Drug Administration (FDA) approved Gleevec (imatinib), a type of tyrosine kinase inhibitor that blocks the protein made by the BCR-ABL oncogene. Similar medications have since been approved that can work when patients develop resistance to Gleevec. Some experts now consider CML a manageable chronic disease. While some patients have successfully stopped taking medication for CML without relapse, the disease generally requires long-term maintenance treatment with oral anticancer therapy, perhaps for a patient’s lifetime. Studies show that adherence decreases over time. Lack of adherence can lead to disease progression, development of medication resistance and, ultimately, risk of death.

Tamoxifen and aromatase inhibitors are the most common forms of hormone therapy for estrogenreceptor- positive breast cancer. They deprive tumors of the estrogen needed to grow by either blocking estrogen’s effects or blocking estrogen production. Hormone therapy can help prevent recurrences and stop or slow the growth of cancer that has spread. These medications are usually taken in pill form once or twice a day. The optimal length of treatment is still under investigation, but hormone therapy is usually taken for five years, and new research has shown a benefit when taken for 10 years. Tamoxifen, which has been in use for more than 30 years, is in a class of medications known as anti-estrogens or selective estrogen receptor modulators (SERMs). It blocks the effects of estrogen in the body. Aromatase inhibitors, including anastrozole, exemestane and letrozole, inhibit the enzyme aromatase, which is part of the estrogen-production process.

Several types of oral anticancer therapy are available to treat metastatic cancer. For example, Sutent (sunitinib), a tyrosine kinase inhibitor, is used to treat metastatic gastrointestinal stromal tumor, renal cell carcinoma and, most recently, pancreatic neuroendocrine tumors. In approving Sutent for this type of pancreatic tumor, the FDA noted that in a large study the drug extended median time until the cancer spread to just over 10 months, compared with around five months for placebo treatment. In 2011, the FDA approved Zytiga (abiraterone acetate) for treatment of advanced castration-resistant prostate cancer, after a phase 3 clinical trial showed that the median overall survival rate was 14.8 months among patients who received Zytiga and prednisone, and 10.9 months among those who received prednisone and placebo. Nexavar (sorafenib), in a class of medications called multikinase inhibitors, is used to treat advanced renal cell carcinoma and unresectable hepatocellular carcinoma. Like in other oral anticancer therapies, studies showed that it offered a small but significant survival advantage of at least several months.

Content

Oral anticancer therapy is available to treat different types of cancer and metastatic disease.

The Right Medicine

Patients may have many reasons for not adhering to their medication regimen, including unwanted side effects, unmanageable cost, simple forgetfulness and a host of psychological issues, such as anger, denial, apathy and depression. But not discussing those reasons can be problematic.

Patients want to please their providers, so at times, instead of telling the truth, they tell us what they think we want to hear,” says Carolyn Blasdel, a board certified family nurse practitioner with the Knight Cancer Institute in Portland, Ore. “I’ve had patients who just don’t want to deal with it or have a fear of criticism or of making the provider angry. And many are just in denial.”

The consequences of hiding nonadherence from one’s care team can be serious, adds Ann Partridge, an associate professor of medicine at Harvard Medical School in Boston. If patients don’t discuss adherence issues, they may not get the benefits of the therapy, which can be significant. “Medications are lifesaving,” Partridge says. “Nonadherence has been associated with increased illness, increased hospitalization and increased costs.”

The solution? Patients mustn’t be afraid to talk openly with their care team about any issues they may have with their oral medications. Most oncologists want only to help and will not judge their patients, Partridge says.

On the clinical side, it is important that providers match education to the patient’s style of learning. For many, a brochure or informational website is sufficient, but some people may have trouble with reading or comprehension and try to hide that fact. “If I suspect that’s the case, I usually discuss things verbally and ask them to repeat what I have told them,” Blasdel says. “It also helps if a family member is there to take notes.”

Communication is key when dealing with barriers of medication adherence.

Psychological Barriers to Adherence

Different strategies for different patients—that’s the way it rolls in the world of oral chemotherapy. If patients find electronic or paper reminders helpful, here are some resources to consider.

Paul Cerrato, editor of InformationWeek Healthcare, recommends a pair of apps for pill reminders. Pillboxie (99 cents at iTunes) lets patients program the time of day for an iPhone or iPad reminder. They can select an icon that’s the shape and color of the pill (say, green and round) and type in the dosage. Cerrato also likes RxmindMe, a free app at iTunes. Patients can take a photo of the pill, plug in dosages, the doctor’s name and other prescription information. See rxmind.me for a rundown of features.

 An online calendar linked to an email account or able to text cellphones can send patients pop-up messages and/or email reminders. All patients have to do is enter information about the pill at the scheduled time of day when they’ll take it. When using electronic reminder systems, however, patients should be aware of a condition that the medical community calls “alert fatigue.” If patients are receiving 10 or 15 daily reminders popping up on their cellphones or computers, they may end up ignoring them.

Patients don’t have to buy a special calendar for pill reminders—a regular workhorse calendar hanging in the kitchen will do just fine. Patients can also check with the pharmacy or doctor’s office&mdash;they may have a calendar tailored for pill-taking with space for recording side effects. The Dana-Farber Cancer Institute offers downloadable pill diaries for once-a-day, twice-a-day, or multiple oral chemotherapies. Patients fill in the time they take the pill and the dosage, and there’s a box where they can track side effects as well. See: 

dana-farber.org/Health-Library/Oral-Chemotherapy-Drug-Diary.aspx

Different strategies for medication compliance are needed for different patients.

Need a Reminder to Take Your Medicine?

Many patients are overwhelmed when facing a cancer diagnosis. The second shock may be from the sticker price of treatment.

Even patients with insurance may be underinsured or face high out-of-pocket costs, especially if they need an oral medication as opposed to one delivered intravenously.

“Many patients are having trouble paying for their oral drugs,” says Erin Moaratty, chief of mission delivery at the Patient Advocate Foundation. A healthcare plan could require a co-pay for oral chemotherapy and also may have a cap on annual benefits. A copay of 20 percent can result in an astronomical sum: $1,800 out of pocket for a $9,000-a-month pill.

Some states require health insurers to cover oral chemotherapy at the same reimbursement rate as intravenously administered treatment, but not every state has such a law. Unfortunately, the Patient Protection and Affordable Care Act does not address this issue, Moaratty says.

Anthony Lacey, a Maryland real estate agent, was barely able to cover the monthly $7,000 tab for his wife’s nine months of oral chemotherapy before she died of metastatic breast cancer in 2011. Because doctors could not find a similarly effective IV option, he exhausted his daughters’ college fund and now must sell his home. As devastating as the experience was, Lacey was committed to helping others in the same boat. He helped push for a new law in his home state of Maryland that resulted in oral chemotherapy being covered to the same extent as intravenous drugs. At least he has the knowledge that his fellow Marylanders will not face the dilemma that he did.

Medicare patients can also get caught in the “doughnut hole”—they have spent $2,800 on prescription drugs that are covered by Medicare&mdash;but it won’t kick in again until $4,550. Until then, the financial burden is theirs.

A patient may decide that the only solution is to cut back on doses. Doctors would prefer a frank conversation about payment problems as they can explain that reduced doses may limit or negate the effect of therapy. In addition, physicians may have resources they can offer to help patients pay for their treatments. Pharmaceutical companies often have patient assistance programs for those who meet certain criteria, such as a fixed income and few resources. Doctors, nurses or a patient navigator or social worker on staff can help steer patients to the right drug company contact, as can patient-oriented organizations, such as the 

Financial aid may also be available from the 

 or a cancer group that supports patients who have a specific cancer type.

Physicians might also have treatment alternatives that are less expensive. “If there’s no way to procure the medication without the patient purchasing it, it’s up to me to make a substitution,” says Lidia Schapira, an oncologist at Massachusetts General Hospital in Boston. “Most of the time I can find a drug that is cheaper, and I do so.”

There are several organizations, companies and institutions that offer financial help to patients for treatment costs. Visit 

Helping patients pay for their cancer mediation can improve compliance.

What if the Medication is Too Expensive?

Of all the roles caregivers fill, one is largely unrecognized. Patients with caregiver support can tolerate more chemotherapy over time, compared with patients who lack support, says Maria Silveira, an internist who specializes in palliative care at the University of Michigan and at the VA Ann Arbor Healthcare System.

In her work with patients receiving intravenous chemotherapy, those who were supported by unpaid caregivers had 60 percent fewer discontinuances of their chemotherapy regimens. Cancer patients who were able to receive their chemotherapy at the dose and for the duration prescribed stood a greater chance of achieving remission, Silveira says.

Oral chemotherapy is convenient, but the downside is the drugs must be taken correctly to be effective, and patients get less face time with the oncology nurse. Caregiver support becomes even more essential to ensure that patients take medications properly and at the recommended dose. Medication adherence rates improve markedly when patients know that someone cares, Silveira says. “Caregivers serve an important role in helping patients feel supported,” she adds.

Caregivers can also be of tremendous service by reading all the printed information that accompanies a prescription. Too often, patients taking oral anticancer therapies may not know how and when to take medications, or whether to do so with or without food, and the label on the bottle, like the prescription itself, may not mention those specifics. Oral anticancer therapies are relatively new for patients and providers, and “there aren’t robust standards in place for making sure patients know how to correctly take their oral chemo,” Silveira says.

Caregivers serve an important role in helping patients feel supported.

She suggests caregivers accompany patients to oncology appointments and bring up any concerns about medication adherence with the oncology nurse or the hospital pharmacist. By being an advocate, a caregiver becomes “the single most valuable tool from a clinical perspective,” she says.

Caregivers need a lot of education, and reliable, easy-to-understand information is sometimes scarce. To try to close the gap, Silveira has developed a web-based reference tool, still in the testing phase, designed to provide advice for managing chemo-related symptoms. The goal is to empower caregivers without disempowering the patient, she says. Caregivers who are well-informed can help patients when their strength to persist wanes.

“We’re asking patients to do a lot when we ask them to self-administer a medication like oral chemo that predictably makes them sick,” Silveira says. When the burden seems too great, patients need someone knowledgeable to provide support and encouragement. “It makes them feel they’re not alone,” Silveira adds.

Caregivers help patients tolerate their cancer treatment better.

Support When It's Needed Most

The medication reminder system Kathryn Kilroy developed for her mother involves placing a dose of pills into small Dixie cups, each cup atop a Post-it note clearly indicating what the pill is for and what time it must be taken. Next to the daily lineup of cups, she leaves a spreadsheet detailing instructions for each dose. The cups are a visual cue, so her mom can see when to take each dose and know whether she actually took it.

Kilroy, who works full-time for a Bostonarea biotech start-up, also calls home around 11 a.m. to ask how she is feeling.

If side effects, such as nausea or constipation, are problematic, Kilroy suggests antidote medications—also laid out and labeled on Post-it notes.

Every two weeks, the regimen changes, so Kilroy creates a new spreadsheet as a reference. She developed this system in the two years since her mom, now 75, received a diagnosis of cancer in her small intestine and was sent home with multiple prescriptions.

“I realized early on that we needed something to organize daily medications because Mom would ask, ‘Did I take that already?’” Kilroy says.

That’s a question that concerns healthcare professionals, too. They know that sending patients home with a laundry list of medications offers no assurance that those medications will be taken properly. The stakes for poor adherence can be dire, particularly as more patients are asked to follow oral anticancer therapy regimens on their own.

As pharmaceutical science advances, the medical profession is racing to better understand why relatively few patients, only about one in five, take oral anticancer drugs as prescribed. It’s partly the complexity of certain drug regimens. Some patients are asked to take multiple pills a day: at bedtime, mealtime, on an empty stomach or several hours apart. Keeping that schedule can be confusing for anyone. For a patient who is ill or fatigued, it can be daunting.

One patient took an oral anticancer pill every day until she finished the bottle, recalls Eric Cohen, an oncology nurse and program manager of patient and family education at Life with Cancer, a service of Inova Health System in northern Virginia. Unfortunately, the prescribed regimen to treat her brain cancer required five days of pills and then three weeks off. “If you take it steadily throughout the month, that’s a serious problem,” he says.

Another patient with lung cancer stopped taking her pills completely after she developed a rash, a fairly common side effect. She didn’t tell anyone, including her adult daughter and caregiver, Cohen says.

Those cases represent just a couple of ways that therapeutic results can be compromised. In the absence of proven strategies to ensure that cancer patients will take their oral anticancer therapy correctly outside a clinical setting, “everybody is flying by the seat of their pants,” Cohen says. At a minimum, he recommends using pillboxes and a treatment organizer.

I realized early on that we needed something to organize daily medications because Mom would ask, ‘Did I take that already?’

In the Stinnett household in Fort Worth, Texas, John Stinnett is practiced at administering medication to his wife, Candice, who has had three occurrences of non- Hodgkin lymphoma. Each time, he approached doling out medication like the organized business analyst that he is. “We used a weeklong pillbox and filled five of the seven holders for a single day,” he says. He created a two-column checklist, indicating when each medication was to be taken, reviewed the checklist while filling the pillbox every morning and checked off pills as she took them. “Eventually you memorize the list,” he says. “After three months, it’s routine.”

Despite the couple’s best efforts, she occasionally missed a pill. Even the doctor expected it. “Every lapse is a possible immune system complication, but you’re going to have lapses,” Stinnett recalls the doctor saying.

The issue of adherence was “surprisingly ignored for a long time” because physicians assumed patients would do what was good for them, says Carolyn Gotay, a professor at the University of British Columbia (UBC) and chairwoman of the Canadian Cancer Society- UBC Cancer Prevention Centre in Vancouver, British Columbia. She has reviewed several studies on adherence rates in long-term hormone therapy and found that adherence rates are less than optimal and fall off over time. Increasingly, medical professionals recognize that good intentions can fail and more research is needed to identify best practices to improve adherence.

Many approaches are possible, such as varying the intensity and frequency of patient education, better counseling by health professionals or pharmacists, simpler written instructions, follow-up phone calls, online assistance, cognitive-behavioral therapy consisting of feedback, reinforcement and rewards, text or phone message alerts, and special pill packaging that monitors activity.

Caregivers at home can help by reminding patients who may be suffering side effects or resisting medication to focus on the ultimate goal and encourage them to talk with other patients—online or in a group&mdash;about their experiences, so they don’t feel alone, Gotay says. Caregivers also can remind patients to tell their physicians and nurses about side effects in case other treatment options are available.

“It’s more effective to help patients problem-solve, rather than try to solve problems for them,” Gotay says.

Even patients who think they are adherent often misjudge. Around two dozen cancer patients whose medication was monitored by a microelectronic device (an “intelligent bottle”) were asked to self-report on their tamoxifen use, and the women overestimated the degree to which they adhered to their oral drug regimen by about 30 percent.

Often it’s a case of “unintentional nonadherence,” says Pamela Ginex, an oncology nurse researcher at Memorial Sloan-Kettering Cancer Center in New York. Patients think they are taking their cancer therapy correctly, and they are not. In an ongoing study, Ginex is examining risk factors that may predict which patients will likely fail to follow an oral anticancer regimen. She and her team will examine patient perceptions of medications in general and inquire about the education they received concerning their medications and possible side effects. Later, the team will interview the same patients to identify methods that worked best to improve adherence.

There’s no single solution for everyone. A reminder alert by phone does not assure a nurse that the patient took the pills. Electronic pill caps can indicate whether the bottle was opened, but there’s no way to know whether a patient took the right dose, Ginex says.

“We have to know what life is like for patients who go home with their cancer treatment and what would put them at risk [of nonadherence],” she says. “Once we know, we need to work on interventions that will help our patients.”

In the meantime, caregivers can help patients by asking the oncology staff for a calendar or schedule indicating what dose and when to start and stop medications. Ginex knows of a patient who leaves a crystal glass by the sink with her oral chemotherapy in it as a reminder to take her pills. Tech-savvy patients can set a cellphone alert, and almost anyone can learn to set the timer on the microwave if pills must be taken with food or on an empty stomach. A call from a family member or friend can be helpful and encouraging. Above all, talk to the patient, and ask what would be most helpful in the way of support.

“Have a conversation, so you’re not overstepping,” Ginex says.

Caregiver support is essential for patients taking oral anticancer therapies.

Adherence Allies

Most cancer patients understand the value of traditional treatments, such as radiation and chemotherapy, and accept the side effects and other issues that come with them. But occasionally some patients reject approved treatment protocols in favor of so-called “alternative” therapies.

“That is nonadherence at its greatest,” says Ann Partridge, an associate professor of medicine at Harvard Medical School in Boston. “They are the nonstarters.” When a patient makes such a request, all the provider can do is explain what the patient is risking.

“Our duty is to explain it to them as best we can,” Partridge says. “If they have a highly curable disease, say earlystage breast cancer that can be effectively treated with surgery, and they decide to take mistletoe instead—which I have seen&mdash;we explain that they are risking their lives by doing this. We explain the odds of the cancer progressing on mistletoe, which would be quite high, compared to surgery, which would greatly decrease their chances of recurrence.”

Carolyn Blasdel, a family nurse practitioner with the Knight Cancer Institute in Portland, Ore., says that when a patient rejects proven traditional therapy in favor of a questionable alternative approach, she tries to talk the individual into trying a complementary therapy that can be used along with standard medical treatment.

“It’s fine to try some of these other things, but let’s work together,” Blasdel says. “It’s OK to try a complementary approach so long as it doesn’t interfere with the traditional treatment. But some people have a real aversion to taking anything artificial and that can be difficult to deal with. Talking about it sometimes works but not always.”

Alternative medicine is nonadherence at its greatest when it comes to cancer therapy.

Alternatives to Adherence?

Like the barber who doesn’t make time for a haircut or a top chef who skips meals, many caregivers fail to care for themselves.

n a survey of 760 self-described caregivers, randomly selected from a national panel of adults, 45 percent admitted that they were more likely to forget their own medications than medications for patients in their care. Compared with non-caregivers, those surveyed were 10 percent more likely to forget to take their medications, 11 percent more likely to stop taking medications if they felt well, and 13 percent more likely to forget to refill their medications.

An AARP and National Alliance for Caregiving study showed that about half of caregivers provide at most eight hours of care every week, and 13 percent provide more than 40 hours per week. Recognizing that caregivers can be overwhelmed, overworked, anxious or tired, the National Cancer Institute (NCI) urges caregivers to take care of themselves for the same reason flight attendants warn adults to put on their own oxygen masks before helping children: Their health is essential to anyone who depends on them. At a minimum, the NCI wants caregivers to do these things:

If those activities are not possible, caregivers should ask for help. Those who report feeling burdened experience declines in physical health, including lower immune function and slower recuperation. Experts also recommend caregivers seek support from family or friends; use time off for self-care; read or listen to uplifting material; pray or meditate; consider joining a support group to learn from others and trade advice; and take prescribed medications.

Remembering to take care of yourself as the caregiver should be just as important as taking care of the patient.

Spring Supplement 2013 | CURE