Pharmaceutical Treatment of the Cancer Pain Patient
Pain is a common manifestation of neoplastic disease. Cancer treatments including cytotoxic chemotherapy, radiation, surgery, and various interventions may contribute in differing degrees to the development of pain syndromes that are often worsened by daily stressors, anxiety, and depression.1 The prevalence of cancer pain increases depending on length of patient survival from time of diagnosis through treatment.2 For example, newly diagnosed cancer patients tend to have a lower prevalence of pain compared with patients undergoing active cancer treatment (25% vs 33%, respectively),3,4 and patients with advanced disease report the highest prevalence of pain (75%).2
This series of articles will review current concepts in the compassionate and multidisciplinary treatment of cancer-related pain—with this article providing a practical guide to pharmaceutical management.
Barriers to Treatment of Cancer Pain
Many national and international cancer care organizations have endorsed the use of opioids for the appropriate treatment of cancer-related nociceptive and neuropathic pain of peripheral origin.5 The success of treatment relies on adequate communication of the intensity and character (including persistent and breakthrough characteristics) of the patient’s pain, as well as realistic treatment expectations and goals, with treatment agreements and informed consent. These communications can be hampered when a patient under-reports their pain because they are in denial about progression of their cancer or when there is lack of correlation between the patient’s and the health care provider’s perceptions of the patient’s pain.6 Determination of the pain generator (Editor’s Note: Part 1 of series) can be associated with a different therapeutic approach or sense of urgency tailored to a patient’s individual pain problem.7
However, there continues to be a global lack of training in pain management for providers, resulting in the educational focus on diseases rather than symptoms. Pain management issues are infrequently highlighted at hospital rounds or educational conferences, resulting in providers’ lack of opioid-prescribing skills including equianalgesic opioid doses. There also continues to be major concerns regarding the regulatory oversight of opioid prescribing, including a recent FDA hearing to reclassify hydrocodone as a DEA schedule II (as recently enacted in New York), which would allow labeling that limits the duration, allow dosing recommendations for opioids used for non-malignant pain, and propose criterion for labeling abuse-deterrent formulations.
The good news is that there is widespread acceptance by pain specialists that opioids are efficacious and should be the mainstay of treatment, particularly for malignant pain.6 Regulatory and law enforcement organizations have recognized that appropriate opioid prescribing is part of the "standard of care" in appropriate patients, and under treating this pain also can be subject to disciplinary action. There are more convenient formulations, including tamper-resistant products. There are FDA-mandated risk evaluation and mitigation strategies (REMS) aimed at providers, patients, and pharmacists to ensure proper education about these medications.8 Many of the concepts presented in this article also may be applied to non-malignant pain.
Why Use Opioids?
Opioid analgesics are an efficacious treatment option for cancer pain. For persistent pain, which requires an around-the-clock (ATC) medication regimen, it is preferable to use long-acting formulations to improve patient compliance with potentially less euphoric side effects and reduced concerns of behavior aberrancies. However, these formulations tend to be more expensive and have a greater risk of causing sleep-disordered breathing (central sleep apnea).9 The dosing frequency may be increased, if necessary, for titration of analgesic control. To treat breakthrough cancer pain (BTP), additional analgesics are prescribed—including short-acting, oral, or rectal opioids—with supplemental rapid-onset opioids, currently classified as transmucosal immediate-release fentanyl (TIRF) products (Table 1). (Editor’s Note: Breakthrough Cancer Pain Treatments).10 In institutions providing palliative care, parenteral opioids—including morphine, hydromorphone, and fentanyl—have been used in conjunction with patient-controlled analgesia.11
As noted, many pain organizations have attempted to facilitate compassionate and effective pharmacologic cancer pain management. Opioids should be considered first-line therapy for patients with moderate to severe pain related to cancer, acquired immune deficiency syndrome, or other life-threatening illness. They should also be considered for any appropriate patients with moderate to severe non-cancer pain.5 This concept has been endorsed by many national and international pain societies including the World Health Organization (WHO). (Learn more about WHO).
The majority of patients with advanced cancer stages (III and IV) have pain, with 54% having pain that is at least of moderate intensity. The "red flag" for investigation of active cancer-related pain is spontaneous onset, particularly with intensification during sleep or lying down. A decision to initiate opioid therapy is based on the severity of the pain, anticipated efficacy, minimization of side effects, stratification of risk of potential aberrancy, and the reasonable alternatives, both pharmacologic and nonpharmacologic. For refractory cancer pain patients, the subcutaneous route (avoiding intramuscular administration) can be effective for the administration of morphine and hydromorphone, and it should be considered a viable choice for appropriate patients unable to receive opioids by oral or transdermal routes, particularly if they are in institutions. Intravenous (IV) infusion should be considered when subcutaneous administration is contraindicated (peripheral edema, coagulation disorders, poor peripheral circulation, and need for high volumes and doses). IV administration should be used for opioid titration when rapid pain control is needed.12 In general, the equivalent IV dose is 1/3 the oral dose, subdural injections are 10 times more potent than IV administration, and intrathecal (subarachnoid) injections are 10 times more potent than subdural administration. Transdermal, rectal suppositories (which may require a compounding pharmacy formulation) or transmucosal delivery systems are preferred in those with alimentary problems (ie, cachexia, dysphagia, nausea, or vomiting).13 A recent meta-analysis has concluded that there are no important differences between morphine, oxycodone, and hydromorphone given by the oral route and that any one of these 3 drugs can be used as the WHO’s first choice in step III.14