Managing cancer pain: Frequently asked questions

Cleveland Clinic Journal of Medicine. 2011 July;78(7):449-464 | 10.3949/ccjm.78a.10054

July 1, 2011|Cleveland Clinic Journal of Medicine

Raghava R. Induru, MD;Ruth L. Lagman, MD, MPH, FACP

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.

HOW DO OPIOIDS RELIEVE CANCER PAIN?

Opioids bind to receptors in tissues throughout the body, including in the central and peripheral nervous systems¹⁵ and the digestive tract. The binding of an opioid to an opioid receptor—including mu, kappa, and delta receptors and orphan receptor-like ligand-1—initiates a cascade of intracellular reactions. Due to the nature of different interactions of opioids with each of these receptors, individuals vary in their response to opioids.¹⁵

WHAT ARE THE CHARACTERISTICS OF COMMON OPIOIDS?

Figure 1. A three-step approach to pain control, based on the World Health Organization’s “analgesic ladder.”

When choosing an opioid, the WHO’s analgesic ladder (Figure 1) offers a simple, three-step approach based on pain severity:

Step 1. Mild pain calls for a nonopioid analgesic with or without an adjuvant (more about adjuvants below).
Step 2. Mild or moderate pain that persists or increases calls for a weak opioid such as codeine, tramadol (Ultram), or hydrocodone, with or without a nonopioid and with or without an adjuvant.
Step 3. Severe pain calls for a strong opioid with or without a nonopioid, and with or without an adjuvant.

Morphine, the prototypical opioid, is well studied and versatile, as it can be given orally, parenterally, rectally, or intraspinally. It is readily available in the United States and Western Europe but not in some parts of the world, such as Asia and Africa. It is also cost-effective.

Hydromorphone (Dilaudid) is similar to morphine in terms of versatility, cost, and effectiveness in pain management. An extended-release form (Exalgo) is now available in the United States.

Oxycodone is readily available in both slow-release (eg, OxyContin) and immediate-release (eg, Oxy-IR) preparations and is also cost-effective. However, there is no parenteral formulation in the United States.

Fentanyl is the only opioid available in the United States that can be given transdermally (in the form of the Duragesic patch) for patients who cannot swallow. Moderate to severe cachexia may affect its absorption. Patients can undergo magnetic resonance imaging while wearing the patch. The patch is readily available and is of moderate cost (Table 2). Oral and buccal preparations of fentanyl are available for control of breakthrough pain, but they are expensive; an inexpensive second opioid is usually prescribed for breakthrough pain.

Methadone is inexpensive and can be used as a long-acting or an immediate-release opioid. However, it should be used with caution in patients with a prolonged QTc interval: in general, a QTc interval of 430 to 450 msec is not a contraindication, but there is a risk of torsades de pointes when the QTc is greater than 500 msec. The physician should also look for drug interactions when prescribing methadone, which is metabolized in the liver via the cytochrome P450 3A4 system. Methadone use can also lead to respiratory depression, prolonged QTc interval, and sudden death.

Buprenorphine can be used as a third- or fourth-tier opioid for patients with both kidney and liver failure. It can be given sublingually or parenterally. It may not be readily available, may not be covered by insurance, and is expensive.

Selecting an opioid to try first

The following are some general considerations when selecting an opioid to try first:

Does the patient have a history of organ failure? Has the patient had a therapeutic response to, or adverse effects from, a particular opioid in the past?
Which route would best fit the patient’s needs? (Oral is always preferable.)
How often will breakthrough dosing be required? (In general, the breakthrough dose is administered at the drug’s half-life, but it can be administered between 1 and 4 hours.)
How much will it cost? (Consider the cost, insurance coverage, and co-pays.)

Table 2 shows different characteristics of commonly used opioids, including route of administration, onset of action, peak effect, and duration of action.¹

WHAT ARE THE EQUIANALGESIC DOSES OF COMMONLY USED OPIOIDS?

Equianalgesic tables are generally used to convert from one opioid to another or from one route of administration to another. There are many published equianalgesic tables, which are inconsistent, variable, and confusing.^18,19 These tables should only serve as a guide, and physicians should use their clinical judgment based on the individual patient.^18,19 All strong opioids are equally effective.

Table 3 lists equianalgesic doses and route conversions of commonly used opioids.^18–20

WHAT ARE THE PRINCIPLES BEHIND OPIOID DOSING?

Successful management of cancer pain depends on using the right opioid in the right dose at the right time.⁵ The starting dose depends on factors such as the type of pain, whether it is acute or chronic, the intensity, whether the patient has previously taken opioids, and whether tolerance developed. There is no evidence to suggest that one opioid is better than another, and there are no fixed formulas for opioid requirements. Appropriate doses are established by titration based on individual analgesic response and adverse effects rather than age, sex, or ethnicity.⁵

Table 4 shows important strategies for opioid dosing. An in-depth discussion of specific opioid dosing strategies is beyond the scope of this article.⁵

References

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