Jeffrey A. Gudin, MD
Director, Pain Management and Palliative Care
Englewood Hospital and Medical Center Englewood, New Jersey
Jeri L. Ashley, RN
Director for Life Planning Palliative Medicine Services Baptist Memorial Health Care Memphis, Tennessee
Charles E. Argoff, MD
Professor, Department of Neurology Albany Medical College Director, Comprehensive Pain Program Albany Medical Center Albany, New York
Vitaly Gordin, MD
Professor of Anesthesiology Associate Vice Chair of Chronic Pain Division Director, Pain Medicine Division Penn State Hershey Pain Management Hershey, Pennsylvania
Marc Rappaport, DO
Medical Oncologist Western Connecticut Medical Group Danbury, Connecticut
Breakthrough pain is a common and disabling reality for patients with advanced cancer. Its root causes vary, and experts agree that this type of pain is often inadequately managed. Treatments are available, yet a greater awareness and understanding of these formulations is needed in the oncology setting. An expert group of pain specialists, together with an oncology nurse and medical oncologist, assembled recently to share insights on therapies to manage breakthrough pain, offering perspectives on diagnosis, assessment, individualized treatment approaches, and patient monitoring.
For the full discussion from this Peer Exchange panel, moderated by Jeffrey A. Gudin, MD, click here
What Is Breakthrough Pain?
Approximately 70% of patients with advanced cancer will indicate pain as their primary complaint, noted Vitaly Gordin, MD. Patients with cancer may experience several types of pain, including sudden-onset pain, chronic pain, and breakthrough pain. In many situations, these patients may experience persistent pain that lasts more than 12 hours per day, which can be controlled with various medications.
However, breakthrough pain, defined by the National Cancer Institute as “intense increases in pain that occur with rapid onset even when pain-control medication is being used,” can result in severe, transient pain flares. “Breakthrough cancer pain comes in very short spurts, and normally doesn’t have a good target to hit,” explained Marc Rappaport, DO.
“It varies from patient to patient,” added Jeri Ashley, RN. “Sometimes it begins and then it progressively gets worse until it’s managed. Other times it spikes and goes back down before the patient even reaches for the medicine bottle.” Breakthrough pain occurs in cancer patients not only with active disease, but also those in remission—for example, patients experiencing postchemotherapeutic effects such as neuropathy, or postsurgical pain, which are the most common pain-related issues in patients receiving curative therapy, according to Rappaport. “There still are breakthrough cancer pain issues that they have to deal with long-term.” As an example, he cited a 40-year-old patient with chronic postmastectomy pain, although her therapy was curative.
Because pain is so heterogeneous, noted Gudin, “the best management of an individual’s pain—including breakthrough pain in cancer— requires a thorough assessment to individualize treatment strategies.”
Among the diagnostic tools available are the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology– Adult Cancer Pain, the Brief Pain Inventory (BPI) developed by Charles Cleeland, MD, for rapid assessment of the severity and impact of pain in cancer patients, and the MD Anderson Symptom Inventory (MDASI).
Numeric rating scales can be employed to assess the severity of breakthrough pain for patients with cancer, noted Gudin; however, in addition to numerical tools, daily activities and medical history should also be considered, such as whether the patient is at the end of the dose or has undertaken new activities, explained Charles E. Argoff, MD. Including these questions in the assessment will provide an accurate measure of the events leading to the breakthrough pain. For example, "Is this breakthrough pain occurring at the end of a person's dose, when they're about to take their next drug?"Argoff continued. "Is the pain spiking idiosyncratically, idiopathically for no apparent reason, which is, of course, less predictable, or is the pain spiking because they're now more active than ever before, being positive, and they're gardening?"
“We need to be very diligent in collecting the history, doing the physical exam, and ordering proper diagnostic studies,” stressed Gordin. He also reiterated that “every new onset of pain should be assumed to be a recurrence of cancer unless proven otherwise.”
Panel members concurred that matching therapies to the particular needs of the patient with cancer is essential in developing treatment plans that will improve the patient’s quality of life.
“The nurse, of all the healthcare team members, probably has more time with the patient than any other, and the opportunities are great for what can be accomplished,” said Ashley. And here, she stressed, building a rapport early on with the patient is critical. She outlined a number of key elements in these patient consultations. For example, “What do they fear? What are their concerns about their pain, their condition, and their opioids (if that is what they are taking)?”
“Listening is a skill that we all need to do better,” Ashley continued, “so that we meet patients where they are; therefore, when they mention a specific pain, we’re able to address it more accurately, based on that assessment.”
Ashley noted that the oncology nurse is often the first to hear from a patient whether or not a pain medication is working. “The nurse giving adequate reports about pain management—both at assessment and reassessment—is critical to informing the physician.”
The reassessment piece is an essential component of effective pain management, continued Ashley. “I cannot stress that enough,” and this must include evaluating every patient for the risk of misuse or addiction. Gudin concurred: “Cancer patients aren’t spared from abuse, addiction, diversion, and misuse issues.”
Choosing Treatment Approaches
“How do we get the oncologists more engaged and educated in the use of rapid-onset opioids,” asked Rappaport, in stressing the importance of including treatments in the rapid-onset class as part of the oncology team’s armamentarium.
In this class are transmucosal immediaterelease fentanyl (TIRF) formulations. Gudin explained that fentanyl agents cross through the blood–brain barrier rapidly, and that there are a number of delivery systems available, though practitioners may not be aware of them.
The original formulation was oral transmucosal fentanyl citrate, said Ashley, which is a rapid-acting lozenge on a stick which patients roll inside their buccal mucosa until pain relief is achieved. This method has yielded good responses in many patients, she added, though in long-term users, there can be detrimental dental effects from the sugar coating.
Newer tablet formulations, including a sublingual tablet, have comparable efficacy within the class, said Gudin. For the cancer population that Rappaport treats, “The sublingual tablet is very useful. I use it initially with some of the esophageal, gastric, and head and neck cancer patients, because the absorption in this area is relatively untouched by the mucositis from the radiation.” An intranasal spray formulation is also available.
Gordin noted that while he does not have experience with the sprays, “It’s a very quick onset, very powerful, one of the most powerful opioid analgesics available. The patient has to wait for a response before delivering the next spray." Physicians need to be very knowledgeable in educating the patient, he stressed.
Argoff underscored the importance of clinician knowledge. “You cannot prescribe these medications without taking a short course and passing it.” TIRF products are only available through an FDA Risk Evaluation and Mitigation Strategy (REMS) program (www.tirfremsaccess.com).
“Each step along the way, there’s mandatory education for everyone involved—the clinicians, the patients, the pharmacist—to promote safe use,” said Gudin. The experts agreed that there is a learning curve with these agents, but as practitioners become more familiar with them and make use of the TIRF-REMS access program, they are likely to become more comfortable prescribing them.
Whatever the preferred delivery route, the clinician must spend time with the patient to go over their titration schedule, “starting low” and then titrating progressively until the appropriate dose is reached, explained Rappaport.
Gudin advises practitioners to pick one or two of the products, and “become fluent with the label, with the package insert, know how to dose them, starting low, and how to titrate them.” “These medications are very potent,” added Gordin, noting that many patients with cancer are elderly and/or are already quite debilitated by the disease itself. Among the concerns in this population, especially, is excessive sedation with respiratory suppression, and as with any opioid, constipation. There is also a risk of a patient falling if started on too high a dose. “These are the most common concerns on the top of my list when I assess a patient and determine the dose.”
Ashley reminded clinicians of safety issues regarding storage. “We talk with patients a lot about lockboxes and keeping the medicines away from children, not driving while using these agents at least until the patient has been cleared by the physician for driving,” she continued, as well as reminding patients to make sure any pets do not ingest them.
Selecting an agent, said Rappaport, is very dependent upon each patient’s specific needs and other side effects. “You just have to keep an open mind as to which one.”
There are also rapid onset anti-inflammatory medications, noted Argoff, with studies pointing to a synergistic effect when a nonsteroidal and an opioid are used in combination. “A patient might actually get even better relief if we advise them to combine (the rapid-onset opioid) with another approach. We have to be creative with the tools we have.”
“Finding the proper agent or combination of agents is very important,” agreed Gordin. “The most powerful agents are opioids, and the majority of these patients, when they come seeking help for pain, they have very severe pain, and we should not deprive them of such a powerful tool as opioid analgesics.”
“Improved quality of life for the patient is what it really comes down to,” concluded Rappaport. “It’s invaluable once you get your feet wet and see how you do make an impact in a patient’s quality of life.”