‘Erosive effect’ of cancer pain can be mitigated by open discussions, individualized control methods
Pain remains one of the most prevalent effects of cancer and its treatments.
Disease-related pain occurs in as many as 86% of patients with advanced cancer and 60% of those on active treatment, according to data published in Journal of Clinical Oncology. Further, 26% to 35% of cancer survivors continue to experience cancer pain.
“The prevalence of cancer pain is difficult to say with great certainty, because the studies are done in different populations,” Judith A. Paice, PhD, RN, research professor of medicine and director of the cancer pain program at Northwestern University Feinberg School of Medicine, told HemOnc Today. “In the very beginning, there is generally pain that causes people to seek some guidance, which can lead to the diagnosis of cancer. Diagnostic tests, biopsies and surgeries can cause acute pain, and there is pain associated with the treatments we use to relieve or cure a patient’s cancer. In cases where a cure is not possible, we are more likely to see pain as the disease advances.”
Patients with chronic cancer pain often initiate long-term pharmacological treatment. WHO created an analgesic ladder in 1986 to determine whether nonopioid pain medication, weak opioids or strong opioids are most appropriate.
However, media coverage surrounding opioid misuse in the United States has prompted many patients with cancer to fear addiction to their pain medicines and request other treatment options. Acupuncture, massage, yoga, meditation and mindfulness practices have all been suggested as helpful alternatives to alleviate cancer pain.
Determining the ideal treatment is essential, as cancer pain often becomes a chronic condition.
“Many of the people who experience pain syndromes will experience them for the rest of their lives,” Paice said. “Not everyone will experience peripheral neuropathy or chemotherapy-induced nausea and vomiting, but if someone does and it persists beyond 6 months to a year, it is less likely to ever resolve.”
HemOnc Today spoke with clinicians and researchers about the need for effective pain management strategies, methods to recognize patients who may be at risk for opioid addiction or misuse, and the promise alternative therapies hold for assuaging cancer pain.
Prevalence of pain
Pain often pervades the treatment experiences of patients with cancer, from diagnosis onward.
It can be difficult for patients to reconcile the fact that the treatments prolonging their lives can also induce chronic pain, Merry-Jennifer Markham, MD, FACP, associate professor in the division of hematology and oncology at University of Florida Health and program leader of the UF Health Multidisciplinary Gynecologic Oncology Program, told HemOnc Today.
“Cancer treatment such as chemotherapy, radiation and surgery can each cause different kinds of pain,” Markham said in an interview. “Postoperative pain is expected after surgery, but this can usually be resolved. Some chemotherapy drugs may cause neuropathic pain.”
Radiation may cause pain in certain situations, Markham added.
“Radiation to the head and neck may cause inflammation and pain in the oral cavity, but we will often use radiation to treat pain, as well,” she said. “Palliative radiation to an area of bony metastasis due to cancer is often a very good treatment for pain in that area.”
Patients may be more inclined to stop treatment if it causes pain, Jennifer A. Ligibel, MD, assistant professor of medicine at Harvard Medical School and director of the Leonard P. Zakim Center for Integrative Therapies at Dana-Farber Cancer Institute, told HemOnc Today.
“Neuropathy, for example, is a very common reason for chemotherapy to be stopped, even when it is working for a patient,” Ligibel said in an interview.
Understanding the degree to which pain affects patients should be an important focus of palliative care, Ligibel added.
“Pain is something that definitely has a very erosive effect on psychosocial functioning,” she said. “When patients are in chronic pain, they are not always able to separate that from their overall mood, which may be why we see a lot of depression and anxiety among patients with cancer.”
In a study published in BMJ Supportive & Palliative Care, Jack and colleagues wrote that pain and depression coexist in 36.5% of patients with cancer. Quality-of-life scores tended to decrease in patients who did not respond to pain interventions, whereas quality of life improved among patients who did respond.
In another study, published in Psycho-Oncology, Janberidze and colleagues found that antidepressant use was more common among patients with cancer who also were taking medication for pain (OR = 2.68; 95% CI, 1.65-4.33).
“Many times, we see people who are in chronic pain, and that creates a spiral of feeling anxious, depressed and often helpless,” Ligibel said. “When you’re having these feelings, they can magnify the symptoms you’re experiencing. Those two elements can play off of each other and make it very difficult for someone to feel better.”
This problem can be magnified among patients with advanced cancer.
“If a patient’s cancer cannot be cured, unfortunately that patient will have pain on and off for the rest of his or her life,” Eduardo Bruera, MD, FAAHPM, clinical medical director and chair of the department of palliative care and rehabilitative medicine at The University of Texas MD Anderson Cancer Center, said in an interview. “They will need to be treated until they die. This can cause physical and emotional pain itself.”
However, Bruera appeared more optimistic about the ability of patients’ pain to resolve.
“If the cancer is successfully treated, the patient will be left with some chronic pain for a while,” he said. “In most cases, the pain will either get much better, or it will disappear completely. In the case of cancer survivors — the patients who can complete adjuvant or therapeutic treatment — the majority are not left with chronic pain syndromes.”
Lack of reporting
Because most patients with cancer may assume that pain is an inevitable side effect, they may be less likely to report their symptoms to their clinicians.
Underreporting of disease- and treatment-associated pain is a major barrier to effective treatment, according to many experts with whom HemOnc Today spoke.
In a study published in Current Opinion in Supportive and Palliative Care, Fairchild reported that patients with cancer — particularly older adults and women — tended to underreport or miscommunicate their pain symptoms to caregivers and health care providers.
“Attitudes about pain may come from one’s own personal belief system about what pain signifies in relation to their disease,” Markham said. “Beliefs about pain also come from broader cultural and societal/community influences. All of these may lead to underreporting.”
Patients’ fears about the consequences of reporting their pain also may keep them from disclosing their symptoms.
“Patients are fearful that they may no longer qualify for clinical trials if they are experiencing pain,” Paice said. “With all of the attention in the media about opioid misuse, there is also such fear that they might be given one of those ‘scary’ drugs, and wonder if those drugs are safe.”
The major consequence of underreporting cancer pain is that it may then be undertreated, Markham said.
“This can lead to worsening physical function, decreased quality of life and psychosocial distress,” she said.
The health care provider should adequately engage their patients in discussions about pain level, Bruera said.
“Cancer pain is most effectively reported when we ask about the severity of pain as part of regular practice,” he said. “When we use the Edmonton Symptom Assessment Scale, nearly 100% of our patients have no difficulty telling us their level of pain on a scale of zero to 10. If we wait for patients to spontaneously complain of pain, then the answer is yes — pain will go unreported or underreported. Conducting universal precautions using extremely simple systems show that patients are quite capable of and very good at reporting pain.”
Breuer and colleagues conducted a study — published in Journal of Clinical Oncology — that found poor assessment tools served as the most important barrier to accurately reporting cancer pain.
“Patients know that their interaction time with health care professionals is limited,” Bruera said. “They want to make sure that the members of their team are going to focus on the most important aspects of their care.
“Many times, patients will be skeptical that their oncology team is there to treat their pain,” he added. “It is important to encourage patients to give their oncologists, nurses and treatment providers a very good picture of how they’re feeling.”
Patients with cancer are commonly prescribed medication — most notably, opioids — for chronic pain.
“The traditional opioids — oxycodone, hydrocodone and morphine — have remained the mainstay of managing malignant pain,” Jai N. Patel, PharmD, chief of pharmacology research and phase 1 trials at Levine Cancer Institute at Carolinas HealthCare System, as well as a HemOnc Today Editorial Board member, told HemOnc Today. “This is primarily because most physicians and clinicians are used to prescribing them, and I don’t anticipate that changing, even as new formulations begin to come out.”
Although opioid medications likely will remain standard for patients with active cancer pain, survivors should be prescribed these medications on a case-by-case basis, Bruera said.
“When you have a tumor that is pressing on other organ structures and causing a great deal of pain, you are almost certainly going to be prescribed opioids,” Bruera said. “Survivors who are having peripheral neuropathy or muscular pain do not need opioids most of the time.”
The use of opioids for pain management has not necessarily led to significant, quantifiable reductions in pain for all patients, Patel said. Only about one-third of patients who receive standard opioids report a reduction in pain — or a decline of two points on the 10-point pain scale — from their first visit to their first follow-up, he said.
“This has been confirmed in large studies, and it has also been shown that between 20% and 25% of patients have worsening pain,” Patel said. “The burden of malignant pain, even among patients with curable cancer, makes pharmacologic pain management a major issue of care.”
Further, adverse events connected with long-term opioid therapy — particularly opioid-induced constipation — remain a concern.
A survey by Coyne and colleagues, published in Frontiers in Oncology, showed that 100% of 31 patients taking daily opioids for cancer pain experienced constipation, with a mean of 4.4 bowel movements per week. Ninety percent of surveyed patients reported relying on medical intervention to facilitate bowel movements, with 65% reporting use of one or more over-the-counter laxatives and 19% using one or more prescription laxatives.
“Constipation is routinely seen in patients with cancer, because they often need much higher doses of opioids than the general patient,” Patel said. “That can become very serious, especially for patients who are suffering from gastrointestinal malignancies, who are probably already experiencing severe abdominal pain and cramping. It isn’t uncommon for patients to go up to a week without having a bowel movement, which can be very painful.”
Endocrine dysfunction also can commonly accompany long-term opioid use.
“These drugs can have an effect on sexual health and on bone health,” Paice said. “There are issues with wound healing and fatigue that are likely related to changes in testosterone. We try to make patients aware that these are the downsides of using an opioid, and if there are alternatives available, we want them to be informed.”
In May, ASCO issued a policy statement addressing the concerns and global accessibility of opioid therapy for chronic cancer pain.
“It is already widely acknowledged that too much pain goes untreated, and while not all patients with untreated pain require opioids, these agents remain an essential part of many pain treatment plans, especially among patients with cancer,” the statement read. “On a global scale, there is mass unavailability of opioids, leading to untold amounts of needless suffering. ... Large-scale proposals currently being considered in the United States could likely exacerbate this problem, and have adverse consequences on patients in need of medically indicated treatments.”
Bruera commended ASCO for the statement.
“It is very important that this conversation takes place,” Bruera said. “It is important that we keep this on the table, because a majority of patients with cancer are going to have to be prescribed an opioid at some point.”
Fear of addiction
Patient fears of opioid misuse and addiction — which can be influenced by media coverage — can create biases against these medications, thereby lessening a patient’s willingness to take them.
“The media is very aggressively covering the opioid epidemic,” Bruera said. “Both patients and their loved ones are frequently distressed about knowing that they need help for their pain, but worried that they will be left in a terrible situation. In recent years, a stigma has grown around taking opioids, which has caused a growing worry, because opioids have been portrayed as being so addictive.”
For instance, reports about the death of the musician Prince, who died of an overdose of the opioid analgesic fentanyl in April, had a rippling effect in the cancer community.
“The day after we learned that Prince had fentanyl in his system, I had many patients in clinic asking me if it was safe for them to be on their fentanyl patches,” Paice said. “The patients hear these things and it puts them to worry.”
These concerns are not unfounded.
The rate of death by opioid overdose increased by 200% between 2000 and 2014, according to data from the CDC. A statistically significant 14% increase in opioid-related deaths occurred between 2013 and 2014, from 7.9 deaths per 100,000 people to 9 deaths per 100,000 people.
The number of fatal drug overdoses in 2014 (n = 47,055) was the largest on record, and 61% of all overdose-related deaths in the United States involved opioids, including heroin.
Most treatment centers have systems in place to identify patients who may be at risk for opioid addiction, which allows clinicians to adequately monitor their patients and recommend treatment only when it becomes necessary, Paice said.
“The physician needs to conduct a thorough pain assessment, but he or she also needs to conduct a thorough risk assessment about the potential for misuse or abuse,” she said. “We need to determine if it is safe to give that individual opioids. If it’s safe, we do so. If there is concern, we employ a lot of strategies to mitigate the risk.”
This risk assessment takes many potential factors into account, such as past and current use of cigarettes, alcohol and recreational drugs.
“It can involve their family history of substance misuse, which serves as a crude proxy for genetic risk,” Paice said. “We also ask about the past history of physical and sexual abuse, particularly for individuals who were abused early in life. These individuals tend to have a high risk for addiction, possibly due to attempts to repress painful memories.”
Overall, health care providers should help deconstruct biases to improve patient access, Bruera said.
“The emphasis on the drug epidemic is starting to have a negative impact on our patients’ ability to receive the appropriate opioid prescriptions and to fill them in their local drug stores at a reasonable cost,” he said. “As oncologists, we need to make sure that our patients continue to receive prescriptions, and have access to the medications they need.”
Traditional approaches to pain management remain the standard.
However, many patients and providers have begun to consider complementary and alternative strategies for treating chronic pain.
These approaches — which include yoga, massage, mindfulness practice, acupuncture and music therapy — are increasingly being evaluated in scientific literature.
A study by Rosenbaum and Velde, published in Clinical Journal of Oncology Nursing, showed that patients with cancer who integrated yoga, reiki or massage into their treatment regimens reported reduced stress and anxiety, improved mood, and better perceived overall health and quality of life.
A randomized controlled study by Palmer and colleagues, published in Journal of Clinical Oncology, showed the integration of music therapy into preoperative practices reduced stress and pain perceptions among women undergoing surgery for cancer.
“Physical therapy and activity are crucial,” Paice said. “Exercise can alleviate fatigue and improve sleep and appetite, and physical activity is key to rebuilding joint and muscular strength. Physical therapy can also go a long way toward aiding those in pain from peripheral neuropathy to have improved balance, preventing falls. It is so important that someone who has been made frail by disease or treatment is guided through physical and exercise options by a specialist.”
The Leonard P. Zakim Center for Integrative Therapies of Dana-Farber — which Ligibel directs — is one of the few dedicated centers for complementary treatments associated with a major cancer treatment facility. The center was inspired by a patient with multiple myeloma who went to great lengths to access complementary therapies while undergoing treatment.
“Lenny Zakim was treated for multiple myeloma at a time when the treatments for that disease were not very effective, and were associated with a high burden of toxicities,” Ligibel said. “He sought out acupuncture and massage as a means to alleviate his pain, and he found himself driving all over Boston to access these services. He wanted to establish a place within a cancer center where these options could be integrated with Western therapies, and where providers could speak to each other about symptoms and try to come up with a more holistic strategy for managing them.”
Since its inception in 2000, Dana-Farber’s integrative therapies program has evolved from a single room to a full-scale program that offers individual services and integrative medicine consultations.
“We also offer group programs that are meant to help patients get back on their feet after cancer treatment,” Ligibel said. “We have programs on movement, tai chi, weight management, meditation and mindfulness, and creative arts. Integrative therapies are very personal for people, so we try to offer a variety of options.”
Increasingly, clinicians are able to offer patients different nonpharmacologic options based on published research.
For instance, in a study published in Cancer, Cassileth and colleagues showed acupuncture can alleviate breast cancer-related lymphedema. In another study, Sprod and colleagues showed a 4-week yoga intervention for older patients significantly lowered cancer-related fatigue, physical fatigue, mental fatigue and global side-effect burden (P < .05 for all).
“We are really starting to see solid research showing the benefit of complementary and alternative services in patients with cancer,” Ligibel said. “When you have an option where a certain approach may alleviate symptoms, you should present the options. If a patient is living with fatigue and there is a therapeutic option that can reduce fatigue, obviously that therapy has a good likelihood of offering benefits.”
Other cancer centers have designed similar programs. Indiana University Health Simon Cancer Center initiated the CompleteLife program, which offers yoga, art and music therapy, massage therapy, and access to social workers.
The Integrative Care Program at Fox Chase Cancer Center offers patients evidenced-based psychiatric care, programs designed for stress reduction and fatigue management, and music therapy and yoga to address anxiety and disease-associated pain. The Lee Jones Lab at Memorial Sloan Kettering Cancer Center is studying the effects of exercise on the long-term physical and mental health of patients with and survivors of cancer.
Still, not all complementary therapies will work for all patients, Ligibel said. Clinicians and patients should work together to determine the best plan.
“Not everything is one size fits all, so it’s important to have a rationale for the modality you are selecting,” Ligibel said. “If you look at the services being offered by an integrative center as a menu, then the rationale of picking and choosing might not make sense, and it might not add much help to the treatment plan.”
The subjective nature of pain makes it especially difficult to address.
“Pain scales are not perfect,” Markham said. “Pain that I experience as a seven may be a five to you, or it may be a 10 to someone else. Pain is a subjective experience, but we should respect the pain that patients are reporting.”
Treatment guidelines and provider education are essential to adequately treat the pain of each individual.
“Education is huge for patients and for clinicians insofar as which medications to select and how to dose them,” Patel said. “At my institution, we have developed pathways not only for tumor types, but for supportive medicine, as well. When we are dealing with mild pain, we can identify the best options to choose from, and then we can move up a level if a patient is experiencing severe pain. We base these off of clinical trial data and national guidelines, and they can be used to disseminate information throughout the entire hospital.”
In July, ASCO released new guidelines on the management of chronic pain in adult cancer survivors.
Among the recommendations, the society stated opioids should only be prescribed for carefully selected patients, and that universal precautions are needed to minimize abuse and other adverse consequences of opioids.
The guidelines also support the use of nonpharmacological interventions such as acupuncture, guided imagery and hypnosis; nonopioid analgesics; and medical cannabis or cannabinoids in states that allow it, after careful assessment of the risks and benefits.
Physicians can play a part in garnering greater acceptance of the benefits of these nonpharmacological pain management and counseling options, Paice said.
“Patients worry that if someone recommends seeing a social worker or a psychologist, then they must be crazy,” she said. “We need to try to normalize this. Psychologists, social workers and others can help patients locate their inner strengths so that they can use the tools they already possess. These are not crazy people. These are normal people going through crazy times.” – by Cameron Kelsall
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For more information:
Eduardo Bruera, MD, FAAHPM, can be reached at email@example.com.
Jennifer A. Ligibel, MD, can be reached at firstname.lastname@example.org.
Merry-Jennifer Markham, MD, FACP, can be reached at email@example.com.
Judith A. Paice, PhD, RN, can be reached at firstname.lastname@example.org.
Jai N. Patel, PharmD, can be reached at email@example.com.
Disclosure: Bruera, Ligibel, Markham, Paice and Patel report no relevant financial disclosures.
Should patients with cancer be offered cannabis as a pain management strategy?
Data have shown that using cannabis as a pain management strategy is safer than relying on opioid medications. We have systems of cannabinoid receptors and endogenous cannabinoids in our bodies that are very similar to endorphins. I believe that we have this system to help us modulate the experience of pain. Cannabis effectively relieves pain, and a small pharmacokinetic study that I conducted showed there was a potential benefit with regard to increased analgesia compared with morphine or extended-release oxycodone.
Similarly, studies have suggested that cannabis has been consistently effective in relieving the pain of neuropathic conditions, including chemotherapy-induced peripheral neuropathy. Neuropathy is a big problem for our patients with cancer; I have a number of patients who are cured of their cancers but remained disabled by their peripheral neuropathy. Animal models suggest that cannabis relieves the pain of peripheral neuropathy, but also may prevent the development of platinum- and taxane-induced peripheral neuropathy in rodents. I am happy to suggest that patients try cannabis for chemotherapy-induced peripheral neuropathy, and I think it would be even better if we had a way to potentially prevent this debilitating condition through pretreatment with cannabinoids.
I am a simple scientist, not a sociologist, so I cannot say whether those who oppose cannabis and medical marijuana are acting on outdated or preconceived notions about its “harms.” Most of us in medicine have been trained in the time when cannabis could not be prescribed. Cannabis was part of the pharmacopeia until 1942; during this time, physicians could prescribe cannabis. But, for the past 76 years, we have not had that ability. When I lecture about cannabis as medicine and ask doctors whether they learned about the endogenous cannabinoid receptor system in medical school, nobody ever raises a hand. That shows the extent of cannabis prohibition and the “Just Say No” campaign. It has become “Just Say No to Knowledge,” and it is a shame.
We are entering a time when medical marijuana can be taken seriously as a pain management strategy. Patients with cancer and their medical providers should welcome this development.
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Donald I. Abrams, MD, is professor of clinical medicine at University of California, San Francisco, chief of hematology and oncology at San Francisco General Hospital, and director of clinical programs at The Osher Center for Integrative Medicine. He can be reached at firstname.lastname@example.org. Disclosure: Abrams reports no relevant financial disclosures.
“Medical” marijuana does not look like a medicine because it is not a medicine. Modern medicine in the United States relies on prescribing specific doses of medicines approved by the FDA for specific medical conditions. The FDA has three criteria for approval: safety, efficacy and purity. Medical marijuana fails on all three counts.
No matter the patient population or the symptoms for which patients are seeking treatment, including disease-related pain, physicians rely on scientific evidence to deliver sound medical practice. Most medical marijuana is smoked. No medicine is smoked for a good reason: Smoking is a toxic and unreliable dose delivery system. Further, there is no medicine for which physicians tell their patients to self-administer as much as they want, in any dose, for any period of time. Real medicines are sold in pharmacies and prescribed by physicians in a long-established and comprehensive system that works to protect patients.
Although medical marijuana is an oxymoron, there is serious scientific interest in the specific chemicals in marijuana. Scientists are seeking to identify their therapeutic potentials, just like all other medicines for the treatment of various medical conditions, including cancer-related pain. Two FDA–approved prescription cannabinoids — dronabinol (Marinol, AbbVie) and nabilone (Cesamet, Meda Pharmaceuticals) — have shown efficacy in the management of pain. Cannabidiol is now being actively studied as an antiseizure medicine. Other cannabinoids may follow.
This conclusion dovetails with the recommendation of the 1999 Institute of Medicine (IOM) report titled “Marijuana and Medicine,” which concluded there is no future for smoked crude marijuana in medicine except in very narrowly defined circumstances, and then only for brief periods of time. The IOM noted that, “if there is any future for marijuana as a medicine, it lies in its isolated components, the cannabinoids and their synthetic derivatives. Isolated cannabinoids will provide more reliable effects than crude plant mixtures.”
I urge physicians who are considering recommending their patients use marijuana for any condition to compare medical marijuana to how true medications are managed — from scientific development to prescribing practices.
As a psychiatrist specializing in addiction medicine, I remind the medical community that marijuana has significant cognitive side effects and abuse potential. Of the 7.1 million Americans with substance use disorders related to illicit drugs, nearly 60% are dependent on or abuse marijuana. The only drug that causes more substance use disorders than marijuana is alcohol.
Among some of the strongest advocates of medical marijuana, there is a surprising lack of support for scientific study of therapeutic potential of cannabinoids for the development of marijuana-based medicines. I can think of only one reason for this: They are interested in labeling smoked marijuana and related unstudied, high-potency products “medicine.” That is their goal, not better health care.
“Medical” marijuana is neither good public health policy nor compassionate health care for the sick.
Center for Behavioral Health Statistics and Quality. Behavioral health trends in the United States: Results from the 2014 National Survey on Drug Use and Health. Available at: www.samhsa.gov/data. Accessed on July 29, 2016.
Institute of Medicine. Marijuana and medicine. Available at: medicalmarijuana.procon.org/sourcefiles/IOM_report.pdf. Accessed July 29, 2016.
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Robert L. DuPont, MD, is president of The Institute for Behavior and Health in Rockville, Maryland. He served as the first director of the National Institute on Drug Abuse. He can be reached at email@example.com. Disclosure: DuPont reports no relevant financial disclosures.