Steve Stricker, PharmD, MS, BCOP

The pharmacist's role can be integral to adequate cancer pain relief and a return of quality of life.

	Despite the availability of many classes of analgesic medications intended to alleviate pain, ranging in intensity from mild to severe, pain remains one of the most frequent and troubling issues encountered by patients with cancer. It is estimated that 30% to 90% of all patients will experience pain at some point during their course of disease, with advanced stages of cancer more commonly associated with pain-related syndromes than early-stage disease.

 More importantly, undertreatment of pain in this patient population is commonplace and can result in significant issues related to quality of life including sleep disruptions, depression, loss of appetite, impairment of activities of daily living, etc.

 Therefore, it should be a priority for health care providers to routinely evaluate and appropriately manage patients for cancer-related pain syndromes.

	Most commonly, pain is assessed by allowing the patient to rate the intensity of their pain using a 0 to 10 numerical scale, a visual analog scale, or a highly simplified Faces Pain scale that has been validated in pediatric patients and other populations incapable of accurately verbalizing their condition. Where possible, in addition to identifying their pain intensity, patients should also be queried to describe the character of their pain, ie, burning, shooting, stabbing, tingling, etc. Combining the pain score with the patient’s description of the pain allows the practitioner to determine the best approach to appropriately manage the patient’s complaints.

	Historically, pain management in cancer patients has been guided by the World Health Organization (WHO) algorithm for initiation of nonopioid and opioid therapy (Figure). This 3-tiered approach relies on the level of patient-reported pain intensity and matches medication therapy accordingly.

 Although this algorithm continues to represent an intuitive approach to management of pain in the cancer patient, it should not replace a provider’s clinical acumen in addressing both acute and chronic aspects of pain management.

	Prior to initiating therapy, it is essential that providers first determine the underlying nature of the patient’s pain syndrome. The majority of cancerrelated pain can be attributed to the location and pattern of tissue and/or organ invasion of the primary tumor(s) or the presence of metastatic disease.

 Mechanistically, this nociceptive-type pain is due to the direct injury of somatic or visceral structures with resulting nociceptor activation. In contrast to nociceptive pain, many cancer patients experience neuropathic pain secondary to their underlying malignancy or as a consequence of their chemotherapy. This neuropathic pain results from spontaneous activation of nerve tissue and frequently responds to therapy with anticonvulsant medications such as gabapentin or pregabalin.

 Once the type of pain, nociceptive or neuropathic, has been determined, the practitioner should continue their assessment by classifying the degree of pain intensity using a scale ranging from mild (pain score of 1-4) to moderate (5-6) or severe (7-10), combined with an assessment of whether the pain is acute or chronic in nature.

	For opioid-naïve patients (ie, those not receiving chronic daily opioid therapy), mild acute pain should initially be managed with acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) at appropriate doses. These nonopioid analgesics are commonly administered orally and patients should be cautioned that daily doses not exceed 4 g per day of acetaminophen or 3.2 g per day of ibuprofen. Additionally, patients should be counseled about the risk of liver toxicity with acetaminophen and risk of gastrointestinal side effects with NSAIDs. Given the antipyretic properties of these drugs, additional warning may be necessary for patients concurrently receiving myelosuppressive chemotherapy due to the concern of masking fevers, which may otherwise be one of the only indicators of active infection in a neutropenic host.

	For patients with moderate to severe pain, opioids represent the treatment of choice with drug selection and route of administration dependent on the level of pain intensity. Where possible, every attempt should be made to start opioids orally at the lowest possible dose that results in pain relief. For patients not having been treated previously with opioids, 5 to 10 mg of oral morphine in an immediate-release form is frequently a suitable starting point for moderate pain. In contrast, severe pain requires a more aggressive approach, with parenteral bolus administration of opioids. Here, an IV dose of morphine 2 to 5 mg should be considered for initial therapy.

 Morphine and the other short-acting opioids (hydromorphone, fentanyl, and oxycodone) may be used interchangeably in equianalgesic doses and are preferred in this setting compared with longer-acting opioids (methadone and levorphanol) due to their ease of titration and time to pain relief (Table).

	For cancer patients who are opioid- tolerant and complaining of acute or breakthrough pain, consideration should first be given to dose escalation of the current opioid therapy. If the patient is unable to tolerate an increase in dose, an alternate opioid should be considered. When rotating opioids does become necessary, consideration must be given to the equianalgesic doses of the opioids and the total daily dose of the new drug should be reduced by 30% to 50% to account for incomplete cross-tolerance of opioids. Otherwise, the patient may experience increased transient opioid side effects that could have been avoided if careful consideration had been given to the patient’s opioid tolerance and overall pain management. Addition of an adjuvant analgesic (eg, NSAIDs, antidepressants) to the patient’s pain regimen may also yield enhanced analgesia for specific pain syndromes (eg, bone pain, neuropathic pain), help to manage opioid adverse events, or in some cases allow the dose of opioid to be reduced.

	It should be noted that adequate pain relief and defining the individual patient’s goal for comfort is important. Rather than achieving a pain score of zero, the identified goal may be a pain score of less than 4 or could involve the identification of a patient’s real world goal of returning to an activity or hobby that their current level of pain is preventing them from enjoying. Once this level of pain relief is achieved, it is essential to convert the patient from short-acting opioids to a manageable oral regimen composed of extendedrelease short-acting opioids, extendedrelease fentanyl transdermal patches, or long-acting opioids.

	Regardless of which analgesic medication is chosen to alleviate the patient’s acute or chronic pain, it is important to recognize that pain management is not a “one size fits all” approach to treatment and practitioners should attempt to tailor therapy to the individual patient.

	Additionally, health care providers should consider some recommendations applicable to all cancer patients with pain.

		Multiple studies have reported that practitioners tend to underestimate the level of pain a patient is experiencing while family members tend to overestimate the patient’s level of pain.

 Therefore, the patient’s report of pain intensity is considered the gold standard for pain assessment and should be believed by the health care provider for purposes of initiating therapy.

		Mixed agonist-antagonists (eg, pentazocine, butorphanol, nalbuphine, etc) should not be recommended due to a ceiling effect limiting their efficacy while also potentially reversing analgesia leading to withdrawal symptoms.

		Patients should be reassessed frequently for response to therapy. For patients complaining of severe pain, reassessment should occur every 60 minutes for oral opioids and every 15 minutes following intravenous administration of opioids.

 Practitioners should not fear increasing the opioid dose or hesitate to consider an alternative therapy in patients with unresolved pain.

		Patients should be prescribed an adequate dose of breakthrough pain medication, often with the immediaterelease form of their long-acting opioid. The rescue dosing may be equivalent to 10% to 20% of the total daily dose divided as frequently as each hour as needed. For patients requiring multiple doses of rescue medication, practitioners should consider revising the daily dose of long-acting opioid to reflect the increasing dependency on opioids to ensure patients receive adequate analgesia.

		Patients may benefit from nonpharmacologic treatment of cancer pain to supplement their pain regimen. These interventions may include hot or cold therapy, massage, music therapy, hypnosis, relaxation strategies, etc.

 Through the addition of these nonpharmacologic treatment modalities, it is possible to reduce the patient’s reliance on opioids and ultimately to improve quality of life.

		Practitioners should be aware of and anticipate adverse events associated with opioid therapy.

	As a class, opioids have common and predictable side effects that include constipation, nausea, sedation, respiratory depression, cognitive dulling, etc. With time, patients will become tolerant to all of these adverse events with the exception of constipation. When initiating opioid therapy, practitioners should ensure patients understand and prophylactically manage bowel issues. This can be accomplished with hydration and the addition of bowel regimens containing stool softeners (eg, docusate) and laxatives (eg, sennosides, polyethylene glycol, etc) titrated to ensure patients continue having regular bowel movements.

	Naloxone, an opioid antagonist, can be used to reverse more serious acute adverse events including respiratory depression. If naloxone is administered, patients should be very closely monitored for obvious signs of opioid withdrawal including agitation, anxiety, tachycardia, sweating, hypertension, etc.

	Cancer pain management is a complex and often arduous task. As a result, pharmacists are frequently called upon in cancer centers to manage these patients. Depending on the institution, pharmacists may be expected to provide medication recommendations for initial pain management, addition of adjuvant analgesics, dosage adjustments based upon organ function, conversion of opioids based on equianalgesic dosing, or monitoring of side effects associated with pain management. Overall, the pharmacist’s role in cancer pain management can be integral to the patient receiving adequate pain relief and a return of the patient’s quality of life.

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Steve Stricker, PharmD, MS, BCOP, is assistant professor of pharmacy practice at Samford University’s McWhorter School of Pharmacy in Birmingham, Alabama.

Steve Stricker, PharmD, MS, BCOP

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