Introduction

Pain management is one of the prime duties of the physician attending a cancer patient. Although 'adequate pain relief' using simple drug treatment has been claimed for 90% of patients with cancer pain, this rate is no often achieved in practice. After full evaluation of the cause and nature of the pain (see companion article, link given below), the best approach to treatment can be selected. The authors of the review summarized here have outlined the choices.

While opioids are the most commonly applied reliefs for cancer pain, it's important to remember that treatment directed at the tumor itself can have analgesic effects.

Radiation and chemotherapy

Radiotherapy is often used for pain control, chiefly in managing bone metastases of lung, breast and prostate cancers; overall responses are usually good - 70% to 80%. The analgesic effects of chemotherapy are less obvious, although symptomatic relief in pancreas and prostate cancer can result from tumor shrinkage; there is often the problem of balancing symptomatic improvement against the anticipated toxicity of the chemotherapeutic agent.

Opioid therapy

The 'analgesic ladder' recommended by the World Health Organization (WHO) is an excellent guideline for selecting the best pharmacological therapy with opioid derivatives. After comprehensive assessment of the patient's pain and his/her general condition, a choice is made of the most appropriate drug to start with. This will depend on age, major organ failure, potential drug-drug interactions, etc.

Next, the route of administration must be chosen. The oral route is usually preferred, but other routes (e.g. the transdermal skin patch) can be used if there is dysphagia or poor gastrointestinal function.

Fixed scheduled dosing has today replaced 'as needed' dosing for continuous or frequently recurring cancer pain. If there is pain that breaks through the schedule, a 'rescue' dose can be added. The initial dosing should have an analgesic equivalence to 5-10 mg of parenteral morphine given every 4 hours. Starting low, dosing can be increased until adequate pain relief is reached or dose-limiting side effects occur. Rescue dose levels are typically 5-15% of the total daily dose.

The frequency of oral dosing can be increased to 1.5-2 hour intervals, if necessary; the minimal interval for intravenous administration can be as short as 10-15 minutes. There is no 'correct' dose or 'maximum' dose for cancer patients; tolerance is rarely the driving force for dose escalation, it's more usually tumor progression.

It's important to know the potency of an analgesic relative to that of morphine, to be able to switch to a new drug if side effects are a problem; the initial dose of the new drug should be typically be reduced from the equi-analgesic dose by 30 to 50% - even more when the new drug is methadone.

Development of side effects is not necessarily a dose-limiting factor. There are numerous therapies for the common gastrointestinal disturbances seen with opioids - nausea, vomiting, constipation.

Non-opioid analgesics

Acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) have dose-dependent analgesic effects, characterized by a ceiling dose above which no further analgesia will occur. They are more effective in inflammatory pain or bone pain than in neuropathic pain. The newer cyclooxygenase-2 selective inhibitors (COX-2 inhibitors) may be superior in avoiding gastrointestinal and renal toxicity.

Some drugs that are not primarily analgesics may have adjuvant pain-relieving characteristics. For instance, corticosteroids, antidepressants, alpha-2 adrenergic agonists (e.g. clonidine), NMDA receptor antagonists (e.g. ketamine, dextromethorphan), anticonvulsants and neuroleptics may each be beneficial in various cases of neuropathic pain. They are usually tried after opioid therapy has been stabilized.

Individual causes of pain may respond to specific drugs: bone pain - bisphosphonates, calcitonin, radiopharmaceuticals; topical disease - capsaicin, local anesthetics; bowel obstruction - scopolamine, octreotide. If a neuropathic complex regional pain syndrome (CPRS) exists, antidepressants, clonidine, prazosin, or phenoxybenzamine may prove useful.

Non-drug therapy

Alternative treatments exist for cancer patients who do not respond adequately to drug therapy. These include mostly specialist interventions:

Approach	Type	Example
Anesthesiologic	Neuraxial infusion	Epidural/intrathecal opioid
		Continuous intraspinal local anesthesia
	Neural blockade	Sympathetic nerve block
Surgical	Neurolysis	Cordotomy
		Neurolysis of peripheral nerve or root
	Neuraxial infusion	Intraventricular opioids
Neurostimulatory	Superficial	Acupuncture
		Counterirritation
	Invasive	Dorsal column stimulation
		Deep brain stimulation
Physiatric	Orthoses	Spinal or limb braces
	Physical therapy	Exercise, heat or cold treatment
Psychologic	Cognitive therapy	Relaxation, distraction, hypnosis
	Psychotherapy	Individual or group, or family therapy

A cancer treatment center or pain clinic is probably the best place for obtaining information and advice on these therapeutic modalities.

Alternative Medicine

Alternative (or Complementary) Medicine is becoming increasingly popular in the search for cancer pain relief, but few controlled studies have been conducted using its methods to bolster the claims of its enthusiasts. Physicians should therefore remain open to such interventions, and be supportive if patients select an option that is probably safe.