Approximately 60% of cancer patients experience pain, and 25% to 30% have severe pain. With some cancers, opioids will be needed before chemotherapy begins and may be more frequently prescribed than chemotherapy. Given the frequency with which pain management is necessary in cancer patients, all oncologists should be familiar with opioid prescribing principles. This article reviews the World Health Organization recommendations for analgesic therapy in this setting, as well as guidelines for opioid therapy in patients with renal failure or hepatic failure, assessment of pain, dosing strategies in both acute and chronic pain, management of opioid overdose, pain associated with dose-limiting side effects, and pain in the actively dying.
Despite significant advances in cancer treatment, pain remains a highly prevalent symptom that negatively affects cancer patients' quality of life. Unrelieved cancer pain can destroy the desire to pursue cancer therapy. Proper pain management is now considered essential to comprehensive cancer care. Yet in a study conducted by the National Comprehensive Cancer Network, we discovered that in comprehensive cancer centers in the United States, pain assessment is not uniformly conducted and analgesic treatment may not be recorded. Clinical outcomes of cancer pain treatment are therefore difficult to evaluate. Although we have certainly made progress in pain management over the past few decades, there is evidence that a significant number of cancer patients still suffer needlessly. The problem of undertreatment of pain in cancer patients remains.
As the authors point out, one of the barriers to adequate cancer pain management is practitioner ignorance of opioid pharmacology. Professional education in pain management is not yet a uniform standard. The authors state that oncologists should be proficient in managing pain, and their article focuses on the clinical pharmacology of opioids. In addition to fully understanding how to prescribe opioids and manage side effects, oncologists are required to educate patients and families regarding the proper use of these very effective and potentially dangerous drugs.
Individualization of Opioid Therapy
Pain is a complex perceptual phenomenon, and the human nervous system is rich with pain-modulating mechanisms, including the opioid system. Exogenously administered opioids interact with naturally occurring receptors in neural and nonneural tissue. There is very wide interindividual variability in responsiveness to exogenous opioids, as discussed in the paper. Tolerability and analgesic efficacy are generally unpredictable. Fortunately, there are several opioid agents clinically available in various formulations. This allows for individualization of opioid therapy.
In clinical practice, opioid medications are titrated to therapeutic efficacythat is, a balance of maximal analgesia with minimal side effects. Expert assessment of pain and analgesic response, and the ability to recognize and manage opioid side effects, are necessary to achieve the best result.
Opioids are the mainstay of cancer pain treatment. Opioids are efficacious for all pathophysiologic types of pain. They are usually combined with other pharmacologic and nonpharmacologic interventions. Nonopioid adjuvant medications are selected on the basis of their known mechanism of analgesic action and the pathophysiology of the pain being treated (a "mechanism-based approach"). Analgesic antidepressant and anticonvulsant medications are often used in combination with opioids particularly for the treatment of neuropathic pain. This complex pharmacotherapy requires frequent patient assessment. Each psychoactive medication should be titrated singly, with close monitoring for adverse effects related to drug-drug interactions and cumulative side effects, especially those affecting the central nervous system.
Aberrant Drug-Taking Behaviors
Another important aspect of cancer pain management not discussed by these authors is the clinician's ability to recognize aberrant drug-taking behaviors and to address them when they occur. Since the use of substances such as tobacco and alcohol increases the risk of certain cancers, oncologists can expect a greater prevalence of substance use in cancer patients relative to the general population. Aberrant drug-taking behaviors represent many clinical possibilities, ranging from taking an extra dose of breakthrough pain medication for a transient flare of pain, to frankly illegal actions such as selling prescription drugs on the street.
Patients with cancer, cancer-related pain, and substance use disorders (or addiction) may be the most challenging patients to manage. They are best served by an interdisciplinary team that includes mental health professionals with expertise in substance use disorders. It is often the case that these patients will need ongoing treatment with opioids and other psychoactive medications for legitimate medical purposes. The oncologist as the treatment team leader should have basic knowledge of the definitions of tolerance, dependence, and addiction. Although properly diagnosing and treating pain with opioids can be complicated in the setting of addiction, it is imperative that clinicians avoid making social and moral judgments that can interfere with proper medical care.
Importance of Guidelines
As discussed in the paper by Davis and colleagues, it has been many years since the World Health Organization promulgated the analgesic ladder. Several studies have demonstrated its effectiveness in controlling much of cancer-related pain. However, given that barriers to proper prescribing of opioids remain, it is important to synthesize the current practice knowledge in a practical guide, as these authors have done.
Opioids remain our most powerful weapon against cancer pain. It is my sincere hope that practicing oncologists will find this practical guide useful and that they will continue to strive to improve pain relief for their patients.
Sharon M. Weinstein, MD
The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
1. Weinstein SM, Romanus D, Lipisto E, et al: Documentation of pain in comprehensive cancer centers in the United States: A preliminary analysis. JNCCN 2:173-180, 2004.