Pain Control in Head & Neck Cancer Patients
Michael Groves, M.D.
May 8, 2008

JB is a 51-year-old male who presented to the ENT clinic with a T2N1M0 squamous cell carcinoma of the right lower lip.  This was treated with wide local excision, neck dissection and reconstruction with a Karapandzic flap.  Despite the fact that perineural invasion was noted on pathology and he was offered external beam radiation therapy as an adjuvant, he refused this.  He was advised of the need for frequent follow-up.  He ignored this and one year later returned to clinic with a local recurrence involving the mandible, floor of mouth, lateral tongue and multiple pathologic neck nodes.  At this point, he was treated with concomitant chemotherapy and radiation with only a 50% response.  His pain levels had increased significantly at that time, and he was requiring Lortab and a Duragesic patch round the clock to control his pain.  Several months later, the tumor had continued to progress and he was referred to hospice for end of life care.  By this point he was requiring ‘round the clock MS Contin for his pain. 

Pain is a very prevalent symptom in cancer patients, especially in those with advanced disease.  Seventy-five to ninety percent of them will deal with pain on a daily basis, and this is a major detriment to their quality of life and their ability to function normally.  We can classify pain in many ways.  One example is describing it in terms of its chronicity.  There are acute, intermittent, and chronic types of pain.  Chronic pain is the most common type of pain in cancer patients and this is often caused by direct tumor involvement of the neighboring tissues.  Cancer patients also experience procedural pain, which tends to be more acute in nature, and is related to surgery or procedures such as lumbar puncture.  Toxicity related to the anticancer treatment modalities, especially chemotherapy, can also induce painful neuropathies in some patients.

There are several mechanisms underlying the production of this sensation of pain.  The first is nociceptive, which is direct activation of the pain receptors called nociceptors.  These send input along unmyelinated C-fibers directly to the CNS, which is perceived as pain.  There is also neuropathic pain, which is caused by abnormal function of the somatic sensory neurons and this can be caused by nerve compression or invasion of the nerve by the tumor.  This causes release of action potential despite the fact that the nociceptors at the nerve endings are not being activated.  There is also a subcellular level derangement of function that can occur with treatment modalities such as chemotherapy that would cause these nerves to be firing and sending pain signals to the brain without direct activation of the nociceptors.  The third type of pain is idiopathic, which cannot be explained by any identifiable pathology.  This may be because of an organic process that the treating physician simply cannot identify.  The other possibility  is that it is more of a functional issue and the pain symptoms are being produced by some psychological process.  A functional source of pain is relatively rare, especially in cancer patients.

Unfortunately, on whole, physicians do not seem to do a very good job treating their cancer patients’ pain.  This was confirmed in a large study by Cleeland et al. in 1994 looking at data from the Eastern and Cooperative Oncology Group.  They were able to demonstrate that of outpatients treated in this group, 42% with recurrent and metastatic cancer were undertreated for pain.  The story gets even worse when they analyzed the data in terms of minority patients, showing that 59% of African-Americans and 74% of Hispanic patients were receiving inadequate analgesia.  That is why it’s very important for us residents to know how to treat patients with cancer pain at a place like Ben Taub, where the vast majority of our patients are members of one of these two groups.  Bernebai et al., in 1998 showed that the same held true for elderly patient.  They looked at a very large group of nursing home patients with cancer and found that 25% to 40% of them had daily cancer-related pain and of those patients with pain, 25% of them received absolutely no treatment whatsoever.  The greatest risk factors for a patient finding themselves in this situation were being very old (> 85) or being a minority.  So, certainly the older, minority patients had very bad luck in receiving adequate pain treatment.

So what are the barriers to treatment of cancer pain?  There are patient related factors such as fear of addiction, fear of side effects, cognitive impairment and depression.  Depressed mood may lead to decreased reporting of pain because the patient simply believes that the doctor will not care about their pain and does not want to here about it.  There can also be linguistic difficulties, i.e. trouble expressing one’s pain symptoms in a non-native tongue.  Some cultural differences may also contribute to inadequate pain reporting.  For example, a belief in the necessity to maintain one’s sense of machismo in Latino culture may limit some patients reporting of their pain.  There are also systemic factors and lack of availability of medications, which is a problem at Ben Taub where as residents we are limited to prescribing weak opioid medicines and if we would like to prescribe a stronger medicine to a patient, we have to track down an attending.  This can be a problem in a busy clinic trying to treat these patients’ pain adequately.  Also there is lack of knowledge by the physician, especially residents, in terms of how to manage cancer pain.  Finally, there is simple failure of the physician to even ask about the pain.

So how should you assess the patient for cancer pain?  First of all, you ask about it at every visit, so that they feel like they can talk about freely with you and you are both on the same team in terms of adequately treating their pain.  You should inquire about the nature of the pain, its chronicity and aggravating/alleviating factors.  It is important to know what methods of relief they have tried in the past, what has worked, what has not worked, etc.  Inquire about other past medical history that may be complicating the picture and psychiatric factors such as addiction history, history of depression and social resources available to them.  Inquire about the patient’s ability to acquire and pay for the medicines you are prescribing them.  We also need to talk in detail to the patient about the goals of their care.  Do they want to prolong the survival at all cost?  Do they want optimize their function or optimize their comfort?  These things are not necessarily all in line with one another and must be laid out explicitly so there is no misunderstanding.  Once you know what your patient’s goals are and what are the characteristics of their pain, you can begin formulating a therapeutic plan.  The first step in treating cancer pain is actually initiating the primary antineoplastic therapies of such as chemotherapy, surgery, or radiation therapy.  Decreasing tumor burden will often decrease cancer related pain.  The next step is initiation of symptom-directed pharmacotherapy.

In 1986, the Wold Health Organization published its recommendations for cancer pain management with something called the analgesic later.  Multiple studies over the last 22 years have sought to validate this model, some have criticized it, but mostly it has stood the test of time and proved to be an adequate treatment model for the vast majority of cancer patients.  It is certainly not perfect, but it does form an effective conceptual framework to work with your patient on creating an individualized plan that can address their pain concerns.  The first step of the ladder is non-opioid analgesics including Tylenol, aspirin and some of the NSAID such as ibuprofen and naproxen.  These often work for a short time in the early stages, but quickly become inadequate as cancer progresses.  The next step would be to move to a weak opioid.  These include codeine, low doses of oxycodone, propoxyphene, Darvocet, and hydrocodone.  These are often prepared as combination products with the NSAIDs.  For example, Lortab, Norco, and Tylenol No.3 are all a very common combination drugs with a weak opioid and an NSAID as an adjuvant.  The next rung on the ladder is a strong opioid, which is for severe pain, not controlled by the previous step.  Morphine, higher doses of oxycodone, hydromorphone, methadone, and fentanyl are all much stronger in terms of their ability to relieve pain and their activation of the opioid receptors.  Even at this step it is worth considering continuing a non-opioid adjuvant such as ibuprofen or Tylenol as these can often open your therapeutic window by decreasing the amount of opioid that you are requiring for the same level of pain relief and decreasing the likelihood that your patients can be experiencing side effects related to that high opioid dose. 

The WHO recommends usage of analgesic medication “by mouth”, “by the clock” and “by the ladder”.  Drug administration by mouth is often the most convenient form for patients and does not require any high level of nursing care like intermittent muscular injections or IV medication would.  “By the clock” refers to a ‘round the clock schedule with rescue doses for acute breakthrough pain to ensure the patient is never left uncovered.  Finally, “by the ladder” refers to the gradual stepwise progression through the therapeutic ladder to avoid unnecessary side effects related to high opioid doses.  As a practical matter, it’s important to know that dosage of non-opioid medication is limited by therapeutic ceiling.  In other words, you cannot expect much higher Tylenol doses to provide more and more pain relief.  There is simply a maximum effect that Tylenol can have in terms of pain relief.  There is also the toxicity issue where usually between 4 g and 6 g of Tylenol in one day could induce hepatotoxicity.  Using high doses of other NSAIDs is associated with gastric ulcer problems and bleeding issues.  The dosage of opioid/NSAID combo products can therefore be increased until you believe that maximum dose of non-opioid component has been reached.  At that point, in order to give your patient more opioid medication you may have to switch to different formulation of the combination drug or switch to a stronger opioid. 

The opioids themselves are limited only by side effects.  So with increasing doses of opioid medication you expect an increasing level of pain relief in a fairly linear pattern.  Opioid dosages are limited by their side effects.  So at very high doses you could expect respiratory depression, sedation, and altered mental status.  You must often use adjuvants to account for the non-lethal opioid side effects effects at lower doses.  Constipation is the most common.  Prescribing the patients stool softeners and laxatives will help them avoid this.  Nausea and vomiting is typically a transitory symptom related to activation of central chemoreceptors in the nausea center of the brain, as well as by GI dysmotility.  It tends to resolve as tolerance to the opioid develops, but in the short term can be treated with anti-emetics and pro-motility agents.  Sedation is very prominent with initiation or escalation of opioids, and one should follow a stepwise approach in dealing with this problem.  Stopping of other CNS depressants, especially alcohol or sleeping pills, is an important step.  You may also consider adding a stimulant.  There are popular ADHD medicines that may give the patient just that little bump up that they need to get through the acute period of increased sedation related to the increasing opioid medication.  The same stepwise approach can be used to deal with confusion as a side effect.  First, eliminate other medicines that might be exacerbating the problem, then try to decrease your opioid dose if possible.  If confusion persists you need to rule out other causes of confusion such as sepsis.  If all these are ruled out, and the patient continues to have delirium related to the high doses of opioids you can try a neuroleptic such as Haldol at low doses.  Rotating your opioids on a fairly regular schedule may help you avoid tolerance to individual medicines and side effects related to metabolic accumulation which at higher levels can become toxic to patients.

You should expect that you are going to be escalating the dose of opioids over time because the patients will develop tolerance to the effects of these medicines and their disease may progress to cause more pain.  Often people get scared to escalate an opioid dose because they feel like it may be a sign of the patient becoming addicted to the medicine.  Addiction is extremely rare in cancer patients.  However, it can be identified through the continued craving of the opioids for the psychologic effects rather than the relief of pain, off-prescription use of the drugs, obtaining from multiple sources such as other physicians, friends, parents etc. and use of these medicines despite harm to self or others.  Dependence, on the other hand, is extremely common and simply refers to the physical development of withdrawal symptoms after rapid dose reduction.  It has nothing to do with addiction, it is simply the biologic process. It is also important to be aware of pseudo addiction, which may be seen in a patient where some sort of increasing psychological stress that leads them to seek out and perseverate about where their pain medication is coming from as they fear it will be cut off from them, even though they truly need it.  This can be eliminated by the physician working to establish an effective therapeutic relationship with the patient, in order to give them the confidence that you, as the physician, care about relieving their pain and will not abandon them to suffer alone.  This may break the cycle of constantly worrying about where the pain medicine will come from.

In conclusion pain is an extremely common symptom in patients with head and neck cancer, and it is far too often under-treated.  Attention should be paid to the patient’s particular emotional and cultural circumstances which may limit their reporting of pain.  The analgesic ladder provides an effective framework for the establishment of a treatment plan that can be individualized your patient’s needs through your empathic, therapeutic relationship with them.  As your patient’s personal and disease-related circumstances change, alterations in the pain relief plan should be made.  Careful attention to the relief of opioid-related side effects, and reassuring your patient that you are dedicated to relieving their cancer-related pain will help the patient avoid behaviors which may be construed as addiction and possibly limit the physician’s ability to appropriately escalate the opioid dosage.

Case Presentation

JB is a 51 y.o. male who presented to the Baylor ENT clinic with a chief complaint of a right lower lip cancer.  Patient had a biopsy of the lesion by a dermatologist, which was positive for squamous cell carcinoma.  He was staged as a T2N1M0 SCCA of the lower lip and was treated with a wide local excision, selective neck dissection and reconstruction with Karapandzic flap. 

Throughout his course he complained of pain at the tumor site, which was relieved somewhat with following surgery after acute post-op pain had resolved.  The patient refused post-operative adjuvant external-beam radiation therapy despite having perineural spread on the pathology specimen. 

He was subsequently lost to follow-up for 1 year and later presented with a local recurrence now involving the floor of mouth, mandible and lateral tongue.  He had significant pain requiring opioid analgesia around-the-clock.  He underwent palliative concomitant chemotherapy and intensity modulated radiotherapy with an incomplete response. 

His pain continued to progress as the tumor grew and he required higher doses of oral morphine preparations to control his pain symptoms.  In February of 2008, the patient elected for referral to hospice care, as surgical resection could not be offered with curative intent. 

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