Managing cancer pain: Frequently asked questions
ABSTRACTFor a variety of reasons, cancer pain is often undertreated, adversely affecting the quality of life for patients and caregivers. To manage cancer pain effectively, physicians need to understand its pathogenesis, how to assess it, how to treat it, and, in particular, how to optimize opioid treatment. We discuss common questions faced by physicians in everyday practice.
KEY POINTS
- Opioids can be used effectively for the management of cancer pain, provided the physician has sufficient knowledge, education, and training.
- Adjuvants, if properly used, can help manage cancer pain more effectively.
- Complementary and alternative therapies look promising, but too little is known about them, so caution is advised when recommending them.
- Patients should be referred to a pain clinic if they have intractable pain or if they have severe side effects from opioid therapy.
- Overall improvement in patient satisfaction and quality of life can be noted when pain is effectively managed.
WHAT ARE THE COMMON ADVERSE EFFECTS OF OPIOIDS?
Adverse effects are among the most common reasons for failure of opioids to relieve pain. If these effects are not anticipated and treated prophylactically, patients may avoid taking their opioid drugs or may complain that they are “allergic” to them. In reality, true allergy to any of the opioids is rare. Patients comply better if they are taught to expect that most adverse effects are either preventable or manageable.21 A simple strategy includes reducing the opioid dose by 25% to 50%, using different opioids (“rotation”), changing the route of administration, and directly treating adverse effects.21,22
WHAT IS OPIOID ROTATION AND HOW IS IT DONE?
Opioid rotation involves changing to a different drug using the same administration route, with the aim of improving the analgesic response or reducing adverse effects.16 It may be useful in widening the therapeutic window, ie, establishing a more advantageous relationship between analgesia and toxicity.16 This strategy applies, for example, to patients who have an adverse reaction to morphine, and who may need rotation to fentanyl or methadone.
The major indication for switching opioids is poorly controlled pain with unacceptable adverse effects due to opioid toxicity, the rapid development of tolerance, refractory pain, or difficult pain syndromes.24 A recent prospective study showed that 42% of patients underwent opioid rotation, and the two most common reasons were inadequate analgesia and severe adverse effects.25 Opioid rotation resulted in relief of confusion (72%), nausea and vomiting (68%), and drowsiness (53%).25
Before trying opioid rotation, review the patient’s pain syndromes and the use of an adjuvant analgesic, and assess for evidence of opioid toxicity or contributing abnormal biochemical factors such as hydration status.24,26 Most opioids are mu-receptor agonists and may exhibit cross-tolerance, a phenomenon in which the alternative drug does not have the expected effects because of similar pharmacologic action of the first drug. Because the degree of cross-tolerance may change as opioid doses are escalated, it is advisable to proceed with caution when switching from one opioid to another in patients who are receiving very high doses. Opioid rotation generally would be ineffective if there is complete analgesic cross-tolerance between opioids.
The common equivalency conversion tables are based either on studies in patients who received low doses of opioids or on single-dose studies.16,24 By substituting opioids and using lower doses than expected according to the equivalency conversion tables (generally a 25% to 30% decrease), it is possible in most cases to reduce or relieve the symptoms of opioid toxicity and to manage patients highly tolerant to previous opioids while improving analgesia.24
Alternatives to opioid rotation are route conversion (oral to parenteral or spinal), addition of an adjuvant analgesic, and opioid dose reduction.
WHAT IS OPIOID TOXICITY AND HOW IS IT MANAGED?
Opioid overdose is commonly the result of an error in pain assessment, opioid prescribing, or dose administration. Opioid overdose classically presents as sedation or respiratory depression. The combination of coma, reduced respiratory rate, and pinpoint pupils is highly suggestive of opioid toxicity, and treatment should be initiated promptly.
This scenario, however, is the extreme example of opioid overdose, and it is rare when a patient is given the correct opioid dose titrated gradually over a period of time. The more common scenario is when a patient’s pain has finally been managed and the patient is resting comfortably with slow respirations. This would not warrant naloxone (Narcan) administration but rather close observation and monitoring of vital signs.
Naloxone has antagonist activity at all of the receptor sites.27 It is important to be alert for acute opioid withdrawal in patients taking high-dose opioids for a long time.27 There are no guidelines as to the route of administration and the dosing of naloxone. Table 6 summarizes the management of opioid overdose using naloxone.5
WHAT IS THE ROLE OF ADJUVANTS?
An adjuvant analgesic is any drug with a primary indication other than pain, but with analgesic properties in some painful conditions. Adjuvants are best used when a patient cannot obtain satisfactory pain relief from an opioid.28 Antidepressants, anticonvulsants, neuroleptics, antiarrhythmics, antihistamines, N-methyl-d-aspartate (NMDA) receptor antagonists, steroids, muscle relaxants, bisphosphonates, and radiopharmaceuticals can be adjuvant agents.29
Adjuvants are generally used to complement the analgesic effects of opioids to achieve optimal pain control with a minimum of adverse effects.28 The following scenarios should prompt the use of adjuvants in clinical practice28:
- The toxic limit of a primary pain medication has been reached.
- The therapeutic benefit of the primary pain medication has reached a plateau.
- The primary analgesic could not be used because of substance-abuse behavior, multiple organ failure, allergy, etc.
- The patient has multiple pain syndromes.
- The patient has additional symptoms unrelated to pain, eg, insomnia or depression.
Table 7 lists adjuvants with specific indications and points to remember when prescribing them.28,29
WHAT IS THE ROLE OF NSAIDs FOR CANCER PAIN?
Nonsteroidal anti-inflammatory drugs (NSAIDs) have a well-established role in treating cancer-related pain, either on their own for mild pain or in combination with opioids for moderate to severe pain, leading to additive analgesia. Using NSAIDs as adjuvants is common practice in certain cancer pain syndromes, such as malignant bone pain, although there is considerable variation in response.31
NSAIDs have long been known to inhibit peripheral prostaglandin synthesis, but recently they have also been suggested to have a central action. The central effect is related to NMDA receptor-induced activation of the nitric oxide system.31
NSAIDs have ceiling effects, and there is no therapeutic advantage to increasing the dose beyond that which is recommended.
Ketorolac (Toradol), indomethacin (Indocin), and diclofenac (Voltaren) have potent analgesic activity, whereas the “oxicam” NSAIDs show predominantly anti-inflammatory effects.30
No NSAID is clearly superior for a particular type of pain. Certain NSAIDs block the NMDA receptor and inhibit cyclo-oxygenase-1 and cyclo-oxygenase-2. There is a poor correlation between the analgesic effects of NSAIDs and cyclo-oxygenase inhibition. There is no evidence to support the use of selective cyclo-oxygenase-2 inhibitors for cancer pain, and these agents have no advantage over nonselective NSAIDs on the basis of limited gastrointestinal toxicity.32
In cancer pain, NSAIDs may delay the development of tolerance and allow lower doses of opioids to be used, with fewer central nervous system side effects.31,32 Despite the extensive use of NSAIDs, relatively few randomized studies have documented their efficacy in cancer pain compared with other chronic pain syndromes. Data on safe and effective doses from studies of nonmalignant pain may not apply to cancer pain, since cancer patients often have several serious conditions and are on multiple medications. In addition, the potential for adverse effects of NSAIDs (gastrointestinal bleeding, renal failure, thrombosis) may be greater in patients with advanced cancer.
In conclusion, NSAIDs may help if used judiciously in somatic pain and visceral pain, and perhaps even in neuropathic pain.31
