15 Feb Head and Neck Cancer Pain: Opioid Use and Alternatives
Written by Jessica McDermott, MD
Introduction
Anyone who currently has or who has survived head and neck squamous cell cancer (HNSCC) can tell you that the cancer itself and the treatment involved can cause significant pain. The location of the tumors as well as the therapies to treat them, including large surgeries, radiation, and chemotherapy, all contribute to this pain. As we are finding more effective treatments for this disease resulting in higher cure rates, it is important to keep in mind short- and long-term side effects and quality of life issues. This article will describe the pain caused by HNSCC treatment, opioid use during this process and why it sometimes can be of concern, and alternative methods to manage pain.
HNSCC pain
HNSCC typically involves sites including the oral cavity (gums, palate, tongue), oropharynx (base of tongue, tonsils), hypopharynx (throat between pharynx and larynx), larynx (vocal cords and surrounding areas) and nasopharynx (are behind the nose). These areas have many nerves, blood vessels, and soft tissue that we need for important functions such as facial movements, swallowing, chewing and talking. Unfortunately, when tumors grow in these sites, they disrupt the nerves and blood vessels which can result in significant pain. Surgical procedures to remove these tumors can exacerbate the pain by direct damage to tissue causing irritation, swelling, inflammation, infection and nerve injury. Radiation, typically given over a multi-week period, also causes pain from inflammation of the mucosa (mucositis) and skin (dermatitis), nerve injury, and fibrosis (scarring). Chemotherapy given with radiation enhances the radiation effect and worsens these side effects. On their own, chemotherapies often used in HNSCC such as cisplatin, docetaxel, and paclitaxel can also cause neuropathy (nerve injury) and muscle aches. The vast majority of patients report pain during HNSCC treatment and a third of patients report persistent pain or other issues effecting quality of life six months out from treatment. Post-treatment pain can be aggravated by cancer recurrence, infections, ongoing tobacco use, dry mouth, acidic or spicy foods and dry air.
Opioid pain medication use during HNSCC treatment
Our group used a national database (SEER-Medicare) of patients to look at opioid use during and after curative-intent HNSCC treatment. Prescribed opioid medications include codeine, fentanyl, hydrocodone, hydromorphone, meperidine hydrochloride, morphine, nalbuphine, oxycodone and tramadol. We found that 83% of patients required at least one opioid prescription during HNSCC treatment. 15% of patients were still requiring continuous opioid prescriptions at 3 months and 7% at 6 months despite being cancer free. While this may not seem like an extremely high number, this is double the national rate of chronic opioid use which is closer to 3-4% of the American population. Our study likely underestimates the true rate of opioid use during and after HNSCC treatment as we were only able to include patients over the age of 65 due to the nature of our database. Younger age is a significant risk factor for persistent opioid use and including younger populations would likely have higher rates. Smaller studies on HNSCC patients have shown rates as high as 30-40% of patients still requiring opioid prescriptions at 6 months after treatment completion. Beyond young age, other risk factors of chronic opioid use include tobacco use, alcohol and other drug use, underlying psychiatric conditions, type of opioid used and length of time on medications.
Why do we care about opioid use for our HNSCC patients?
While nobody wants our HNSCC patients to be in undue pain, and opioids certainly have their place as part of our treatment, they also have concerning short- and long-term effects that should be taken into consideration. In the short-term, opioid medications can cause symptoms such as constipation, nausea, vomiting, headaches, rashes, insomnia, fatigue and lack of appetite. Older patients can have slowed and less effective breathing. Overall quality of life is also reported to be lower compared to similar patients not taking opioids.
Along with a continuation of the short-term side effects, chronic opioid use can result in depression, sleep-disordered breathing, cardiovascular issues, sexual dysfunction and other
endocrine issues, and increased sensitivity to pain. Some studies even show decreased survival rates for cancer patients on opioids and increased growth of cancer cells in the presence of opioids in the laboratory. Of course, there are also the additional concerns for addiction and overdose. 2.5 million Americans have an opioid use disorder and on average 130 people die in the United States daily from opioid-related issues. 40% of these opioid overdose deaths involve prescription opioids. It is important to distinguish between opioid dependence and addiction (or opioid use disorder). A physical dependence can occur when people have been on an extended course of opioids and the body requires external opioids to prevent withdrawal. This can typically be managed with a slow taper off of the medication. Opioid use disorder, on the other hand, can present as uncontrollable cravings for the drug or inability to control drug use despite possible harm to oneself or others. This is more difficult to treat and often requires the combination of medication use (such as methadone and buprenorphine), therapy, and close follow-up with a pain and addiction specialist. Risk factors for developing an opioid use disorder include high doses of opioids, use > 90 days, age <65 years old, current pain, insomnia, anxiety/depression and illicit drug use.
Beyond the short- and long-term side effects of opioids, multiple studies have shown that they may not be very effective at managing chronic pain. While they can allow for better pain control in the acute setting, there is not good evidence that they provide long term pain control benefits compared to non-opioids and non-pharmacological methods of pain management.
If it is determined that opioids are needed for pain control as part of a treatment strategy, then a careful plan should be put in place to manage short- and long-term side effects. If feasible, an eventual plan for weaning off of these medications should also be addressed when the worst effects of treatment are waning. If the HNSCC is persistent or recurs, then use of opioids may be unavoidable and weaning not possible.
What other strategies can we use to manage HNSCC pain?
There are multiple other medications and therapies that can be used as an alternative or in addition to opioids to manage and prevent pain due to HNSCC and its treatment.
Acetaminophen and Non-Steroidal Anti-Inflammatory Drugs (NSAIDS)
Acetaminophen (Tylenol) and NSAIDS (including Aspirin, Ibuprofen, Naproxen, Celocoxib, etc.) are often useful in mild to moderate pain, particularly with an inflammatory or musculoskeletal component. These medications can often be used before treatment pain becomes severe or as a bridge off of opioid medications. Several studies have also found that use of NSAIDS or acetaminophen alongside opioid medications may increase pain control and allow for lower opioid doses. NSAID use should be monitored for gastrointestinal side effects (nausea, cramps, ulcers, etc.) and kidney function, particularly if taking around the clock. Acetaminophen use should be kept to less than 3,000-4,000 grams per day and monitored for liver injury.
Gabapentin/Pregabalin
Gabapentin (Neurontin) and Pregabalin (Lyrica) are medications categorized as anticonvulsants as they were initially developed to stop seizures. They are typically used in the pain field to address nerve-related pain and have been largely studied in patients with diabetic neuropathy, though both have been looked at in HNSCC. Gabapentin is usually started at a low, nighttime dose and is titrated up to be taken as much as 3 times a day if tolerated. It has been shown to decrease pain and mucositis after radiation and improve swallowing outcomes.
Some people do have difficulty tolerating gabapentin due to side effects of dizziness, drowsiness and fatigue. Pregabalin is more expensive and typically reserved by most insurances for second-line treatment for people that do not tolerate gabapentin or in whom it does not work. When studied in HNSCC patients receiving radiation, it was found to significantly decrease pain severity and improve mood and quality of life. Pregabalin is generally tolerated better than gabapentin, but can also cause the side effects of dizziness, drowsiness and fatigue.
Antidepressants
Several drugs developed as anti-depressant medications have also been found to have some effect in cancer pain management. The two major groups are tricyclic antidepressants (TCAs, such as amitriptyline and nortriptyline) and serotonin and norepinephrine reuptake inhibitors (SNRIs, such as duloxetine and venlafaxine). Neither type has specifically been studied in HNSCC, but both have been shown to significantly reduce nerve pain as well as improve anxiety, depression and insomnia in other types of cancers. TCAs can have significant side effects such as drowsiness, dizziness, dry mouth, and constipation that can occasionally limit their use. The SNRIs tend to be better tolerated though can still cause nausea, drowsiness, and dry mouth.
Corticosteroids
Corticosteroids, including dexamethasone and prednisone, can sometimes be given in short courses, or bursts, to help decrease inflammation contributing to pain. They can relieve the mucositis and swelling in the mouth, neck and throat and often can help with appetite and energy levels.
Typically, patients should not be left on steroids for more than a few days to several weeks as long-term use can result in many issues including high sugar (glucose) levels, infection risk, poor healing, swelling, gastrointestinal issues, etc.
Rehabilitation
Physical therapy (PT), occupational therapy (OT), and speech therapy (ST) all have multiple positive effects on functional outcomes and quality of life during and after HNSCC treatment. HNSCC patients that participate in these therapies have improved swallowing outcomes, better nutrition, higher physical function and muscle endurance, and less fatigue. By increasing function and decreasing swelling and scar tissue, these therapies have repeatedly shown to prevent and decrease pain. If possible, meeting with these therapists early in the treatment course before symptoms develop can prevent or decrease some of these side effects and certainly should be incorporated as part of a post-treatment HNSCC survivor plan.
Exercise
Physical activity, whether done as an individual or under guidance, is increasingly thought to be an important part of cancer treatment and survivorship. Activities such as walking, yoga, swimming, low-impact cardio, and non-heavy weight lifting have all shown similar benefits to rehabilitation as well as improvements in mood and tolerance to treatment. Consistent exercise participants regularly report lower levels of pain.
These patients also have lower rates of cancer recurrence and cancer deaths. It is important to discuss type and rigor of planned exercise with your doctor, but most low impact activities should be well tolerated during and after HNSCC treatment.
Alternative/Complementary Medicine
There are many other alternative and complementary medicines and techniques that may impact cancer and treatment related pain. Massage and acupuncture in particular have been studied in cancer patients and may provide significant pain relief to some. Many other devices and medications such as herbal remedies, antioxidants, and cannabinoids can be purchased for possible pain relief. Most of these are not well studied or regulated yet, though scientists and doctors are increasingly looking at these for possible non-opioid options. Your doctor should be aware if you are using any of these remedies to ensure they will not interact with your current medications and treatments.
Conclusion
Most patients with HNSCC report pain at some point due to the location of their cancers and the rigorous treatments they are put though. Opioid medications have been widely used to manage this pain, but we are becoming increasingly aware of the short- and long-term side effects as well as the risk of disordered chronic use. It is very reasonable to continue to use opioids for HNSCC, particularly for severe pain, but patients and their doctors should be aware of the risks and have a long-term pain management plan in place. Using non-opioid medications and therapies alongside opioids may reduce the opioid doses needed and may target the pain in different ways (such as addressing nerve pain). These other medications and methods can also be used to help taper off of opioids as tolerated when the treatment-related side effects start to decrease.
Managing pain control is best done as a multi-disciplinary team with patients heavily involved to avoid suffering while also being mindful of all the modalities to address it.
Editor’s Note: Jessica McDermott, MD received her MD at Medical College of Georgia followed by residency at Emory University and fellowship in hematology/oncology at the University of Colorado. She is currently an assistant professor of medicine at the University of Colorado and also works at the Denver VAMC. Her clinical and research focus is on head and neck cancers – participating in and developing clinical trials and researching ways to improve quality of life and long term outcomes in these patients.