Management of Breakthrough Pain Due to Cancer

The most frequent pattern of pain related to cancer and cancer treatment consists of continuous pain punctuated by episodes of worsening pain. The cancer pain guidelines developed by the Agency for Health Care Policy and Research (AHCPR) recommend a pharmacologic regimen administered on a regular schedule for continuous pain supplemented by as-needed (prn) analgesics for episodic exacerbations.[1] The term “breakthrough pain” has gained widespread use to define episodes of moderate or severe pain that are short-lived (lasting a few minutes to several hours) and that occur against a background of well-controlled pain. Efforts to better characterize breakthrough pain[2] have improved the general understanding of the daily exacerbations of cancer pain and our skills in devising effective analgesic regimens.

Such a broad definition carries the risk of undermining the importance of the pathophysiology of pain, and, consequently, individualized and effective treatment options may be overlooked. This risk is exemplified by the review by Simmonds, in which the emphasis is restricted to the search for a rapid-onset, short-acting opioid delivery system that would effectively treat breakthrough pain, regardless of the underlying pathophysiology.

Spontaneous vs Triggered Breakthrough Pain

Breakthrough pain can be sub-divided, as indicated by Simmonds, into spontaneous pain and triggered pain. Although the pathophysiology of some breakthrough pain episodes may remain somewhat unclear, a more or less approximate explanation can be devised in most cases.

Breakthrough pain and background pain commonly share the same pathophysiology, location, and etiology. A percentage of “spontaneous” breakthrough pain episodes, on second analysis, may reveal one or more triggering factors that are amenable to individualized treatment strategies that can augment the efficacy of rapid-onset, short-acting opioids.

Although analgesics should be started as soon as possible, a thorough assessment of the pain complaint can often guide a more effective, individualized treatment approach.

Predictability is an important characteristic of breakthrough pain that needs to be considered when trying to devise a treatment regimen for this type of pain. The pains associated with dressing changes or planned activities are examples of predictable pain for which the timing of analgesic rescue medications is crucial. In such cases, the timing can be altered ad hoc to match the predicted onset of pain (taking into account the time needed drug absorption).

Bone Pain

Bone pain is a frequent cause of episodic pain exacerbations in cancer patients. Nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, pamidronate (Aredia), and radiopharmaceutical agents can all decrease the frequency and intensity of episodic bone pain.

Nerve blocks may be indicated in selected patients. (For example, intercostal nerve blocks in patients with pathologic rib fractures can relieve pain associated with inspiration or cough.) Epidural administration of local anesthetics can help patients with multifocal sites of bone pain, either spontaneous or triggered by movement. Patients with spinal instability or impending long bone fractures may benefit from orthotic devices or surgery. Of course, specific contraindications exist for each one of these treatments, and an individualized approach is fundamental.

Neuropathic Pain

Neuropathic pain also is often continuous with intermittent exacerbations. Not uncommonly, attacks of lancinating pain occur spontaneously in patients with post-herpetic neuralgia or post-radiation plexopathy. These paroxysmal pains are best prevented by anticonvulsants, although tricyclic antidepressants, lidocaine, mexiletine, and clonidine may also decrease their intensity and frequency. When movements, such as arm swings, trigger neuropathic pain, as may occur in patients with brachial plexopathy, an arm sling may be very helpful. When neuropathic pains are triggered by a light touch, such as the constant skin brushing from clothing, a local anesthetic cream, such as lidocaine/prilocaine (EMLA), may be helpful.

Finally, cognitive techniques, such as relaxation training, hypnosis, imagery, and distraction, may help relieve breakthrough cancer pain in selected patients.[3]

Summary

Breakthrough pain is a complex, multifaceted phenomenon that is an integral part of most cancer pain syndromes and affects the majority of patients with cancer pain.

The suggestions listed above are by no means a complete list of the analgesics that physicians may use to treat breakthrough cancer pain. Rather, they are examples of the wide variety of available strategies, and they underscore the need for a comprehensive, individualized, dynamic assessment.

Having said all of the above, a fast- and short-acting opioid delivery system that more precisely coincides with the intensity and time course of breakthrough pain episodes, as illustrated by Simmonds’ figures, is certainly a good addition to the cancer pain specialist’s “bag of tricks.” There is good evidence that oral transmucosal fentanyl citrate (Actiq) provides rapid pain relief when compared to placebo.[3] Controlled studies comparing oral transmucosal fentanyl to the usual rescue opioids (eg, morphine, oxycodone, and hydromorphone) will help the practitioner decide whether the higher cost of transmucosal fentanyl is offset by its more rapid onset and more effective analgesia.

References:

1. Jacox A, Carr DB, Payne R, et al: Management of Cancer Pain. Clinical Practice Guidelines no. 9, AHCPR publication no. 94-0592. Rockville, Maryland, Agency for Health Care Policy and Research, U.S Department of Health and Human Services, Public Health Service, March 1994.

2. Portenoy RK, Hagen NA: Breakthrough pain: Definition, prevalence, and characteristics. Pain 41:273-281, 1990.

3. Portenoy RK, Payne R, Coluzzi P, et al: Oral transmucosal fentanyl citrate (OTFC) for the treatment of breakthrough pain in cancer patients: A controlled dose titration study. Pain 79:303-312, 1999.