As oral cancer drugs gain, dosage problems grow
Velda Model had endured two surgeries to remove a tumor from her breast, along with chemotherapy that numbed her fingers and toes and radiation that left her chronically weary. So when the pills that were supposed to help ward off cancer's return made her body ache and her heart race, the North Shore woman took matters into her own hands: She stopped taking them.
"I just can't live like this," Model said she told her nurse practitioner last February. Her oncologist eventually convinced her that the benefits of taking the oral hormone therapy Aromasin outweighed the discomfort, but Model had learned firsthand why so many cancer patients don't follow doctors' orders.
Cancer-fighting medicines are increasingly available in pill form, giving patients far more control over their care in a field long dominated by drugs delivered through intravenous tubes at clinics or hospitals. Last year alone, the US Food and Drug Administration approved five new oral cancer treatments, and a quarter of the cancer drugs under development are capsules or tablets. Intravenous treatments are still the norm, but oncologists are rapidly increasing the number of oral treatments they prescribe, especially for certain cancers such as breast tumors, for which most survivors receive pills for up to five years after initial chemotherapy.
As a result, cancer patients increasingly receive at least some of their medications at home, and can sometimes go weeks or months without checking in at the cancer clinic. In addition to the convenience, oral treatments tend to cost less and some newer medicines have fewer side effects than conventional chemotherapy.
But the take-at-home arsenal greatly increases the risk of underdoses, overdoses , and just plain mistakes as patients wrestle on their own with unpleasant side effects, complex treatment plans, and simple cancer fatigue. More than half of patients taking one widely used oral chemotherapy, Xeloda, occasionally cut back their dose or take a medication "break" to reduce side effects such as nausea and skin irritation, according to a survey of oncologists. A pancreatic cancer patient taking Xeloda explained how he managed his medication : "I take the pills until I develop a funny rash on my hands and then I back off a little bit."
Cancer specialists are only now waking up to the scope of the "non adherence" problem, and one-quarter of cancer centers don't have a formal system to track patient compliance with their oral treatment plans, according to a survey by Dana-Farber Cancer Institute researchers published in the British Medical Journal last month. In addition, many centers don't take as many safety precautions for oral treatments as they do for the intravenous infusions given under the watchful eye of staff members.
"There was an inclination to write a prescription for these [oral cancer treatments] like a physician would write a prescription for Pepcid or amoxycillin, but the routine safeguards weren't in place," said Dr. Saul Weingart , vice president for patient safety at Dana-Farber and lead researcher on the new study. Doctors must provide elaborate details about their IV drug orders and have a second physician review them to avoid mistakes, he said, but most cancer centers have no such requirements for pills.
The risk to patients is substantial. If they take too much chemotherapy, hormone treatment, or other cancer medicines, they risk a toxic reaction or long-term damage such as hastened osteoporosis or heart damage. If they take too little, they lose protection against cancer. Women with hormone-responsive early breast cancer -- by far the most common type -- increase the risk of cancer recurrence by up to 50 percent if they don't take five years of hormone therapy pills.
But it's not a simple problem to solve, in part because there are so many reasons that patients don't take medicine as prescribed. Even when people try to follow directions, they can still make significant errors. University of Washington researchers recently found that 1 out of 5 parents made mistakes in giving oral medications to their children with acute lymphoblastic leukemia.
"This concept of oral therapy is so new to us, nobody has figured out the best way to educate the patient," said Dr. Susan Goodin , director of pharmaceutical sciences at the Cancer Institute of New Jersey, who believes cancer specialists need to learn from fields such as diabetes care how best to get patients to follow instructions. "There is no standard out there."
Until recently, oncologists generally assumed that cancer patients followed doctors' instructions religiously, if only because their lives often depend on it. But Dr. Ann Partridge of Dana-Farber, Model's oncologist and co author of the study on safety precautions at cancer centers, said cancer patients often deviate from their prescriptions, especially when the immediate cancer threat recedes. Her review of research on cancer patient "non-adherence" found that up to 80 percent failed to strictly follow their prescriptions.
"Clinicians notoriously overestimate the impact they have on patients' behavior," said Partridge, noting that cancer patients' long-term compliance is similar to patients taking drugs for other chronic conditions such as high blood pressure. "Over and over when we look at things from exercise to whether they take their pills or make dietary changes, it's very difficult to change behavior."
A new study by researchers at Trinity College in Dublin found that 35 percent of breast cancer survivors stop taking hormone treatment pills after 3.5 years despite strong evidence that five years of the treatment -- which prevents the hormone estrogen from reaching cancer cells -- saves lives.
Women under 45 and women over 75 were most likely to cut back or stop taking the pills, but probably for very different reasons. The older women were frequently on medication for other health conditions, raising the risk of mistakes, confusion, and side effects caused by drug interactions -- all of which could cause a cut back on hormone therapy. But the authors speculated that younger women stopped because they disliked the hot flashes, mood swings, and nausea that are common side effects.
"Younger women may be more likely to experience side effects, and with a more active lifestyle, they may be less willing to put up with them," said Thomas Barron, lead author of the study in the March 1 issue of the journal Cancer.
Nonetheless, the trend toward oral cancer treatments is expected to grow rapidly, especially now that the Medicare drug benefit covers most oral cancer treatments; previously, only a handful of oral drugs were covered. Moreover, surveys show that patients strongly prefer pills over IVs, both because of pills' convenience and patients' dislike for needles.
Oncologists, who generally get lower insurance payments when they prescribe pills than for IV treatments, are nonetheless increasingly willing to prescribe them: 80 percent of oncologists told health care analysts at Decision Resources, Inc., that their use of oral treatments increased from 2003 to 2005. That is in part because many newer oral treatments target cancers with exceptionally high death rates, such as advanced colon and kidney cancer, for which there are few effective treatments.
Weingart suggests that cancer centers need to check in regularly with their patients taking oral medications to be sure they're not suffering serious side effects, and a growing number of oncologists ask patients to either keep a diary of their treatments or bring the pills to doctors' appointments so that someone on the staff can verify that they've taken the right number. Dana-Farber now applies the same safeguards to oral and IV chemotherapies, such as putting the dose on the label and writing prescriptions electronically, and the staff reviews patient compliance with prescriptions at each hospital visit.
Unfortunately, Goodin of the New Jersey cancer institute in New Brunswick, N.J., said patients can't always be counted on to admit when they have cut back on medications, and they may be embarrassed enough to cover up their lapses. "Patients want their doctor to be proud of them," she said.
Ultimately, there is no substitute for open communications like Velda Model has wiith Partridge. In the two years since she was diagnosed with breast cancer, Model has contacted Partridge's office when she has suffered severe side effects, even notifying her doctor when she stopped taking her hormone therapy, Aromasin, for two months. That openness allowed Partridge to suggest alternatives -- and to persuade her patient that it was a bad idea to drop hormone therapy altogether.
Today, Model has reduced the flu-like symptoms from her hormone treatment by taking the pills after dinner rather than before, but she said some discomfort may be the price of remaining cancer-free. "The drugs are really terrible, but when you consider the alternative, you just have stick it out," she said.
Scott Allen can be reached at allen@globe.com. 