Pain (PDQ®): Supportive care - Health Professional Information [NCI] - Pharmacologic Management
Basic Principles of Cancer Pain Management
The World Health Organization (WHO) has described a three-step analgesic ladder as a framework for pain management. It involves a stepped approach based on the severity of the pain. If the pain is mild, one may begin by prescribing a Step 1 analgesic such as acetaminophen or a nonsteroidal anti-inflammatory drug (NSAID). Potential adverse effects should be noted, particularly the renal and gastrointestinal adverse effects of the NSAIDs. If pain persists or worsens despite appropriate dose increases, a change to a Step 2 or Step 3 analgesic is indicated. Most patients with cancer pain will require a Step 2 or Step 3 analgesic. Step 1 can be skipped in those patients presenting at the onset with moderate-to-severe pain in favor of Step 2 or Step 3. At each step, an adjuvant drug or modality such as radiation therapy may be considered in selected patients. WHO recommendations are based on worldwide availability of drugs and not strictly on pharmacology.
Analgesics should be given "by mouth, by the clock, by the ladder, and for the individual." This requires regular scheduling of the analgesic, not just as needed. In addition, rescue-doses for breakthrough pain need to be added. The oral route is preferred as long as a patient is able to swallow. Each analgesic regimen should be adjusted for the patient's individual circumstances and physical condition.
Acetaminophen and Nonsteroidal Anti-inflammatory Drugs
NSAIDs are effective for relief of mild pain and may have an opioid dose–sparing effect that helps reduce side effects when given with opioids for moderate-to-severe pain. Acetaminophen is included with aspirin and other NSAIDs because it has similar analgesic potency, though it lacks peripheral anti-inflammatory activity.[Level of evidence: I] Side effects can occur at any time, and patients who take acetaminophen or NSAIDs, especially elderly patients, should be followed up carefully.[3,4,5] There is growing debate about whether NSAIDs are useful and have significant opioid-sparing effects. One meta-analysis  suggests that the usefulness of NSAIDs is limited and that they do not significantly spare opioid doses. Another study suggests that NSAIDs are useful and reduce the need for opioid dose increases; however, only patients with pain progression after 1 week of opioid stabilization were selected for the study.[Level of evidence: I] Patients taking NSAIDs are at risk for platelet dysfunction that may impair blood clotting. Table 1 lists NSAIDs with minimal antiplatelet activity.
The coxibs are a subclass of NSAIDs designed to selectively inhibit cyclooxygenase-2 (COX-2). Development of these drugs was based on the hypothesis that COX-2 was the source of prostaglandins E2 and I2, which mediate inflammation, and that COX-1 was the source of the same prostaglandins in gastric epithelium, with the potential advantage of less gastrointestinal ulceration and bleeding and the absence of platelet inhibition over traditional NSAIDs. Direct comparisons between COX-2 inhibitors are few. A systematic meta-analysis of COX-2 inhibitors compared with traditional NSAIDs or different COX-2 inhibitors for postoperative pain suggests that rofecoxib, 50 mg, and parecoxib, 40 mg, are equipotent to traditional NSAIDs for postoperative pain after minor and major surgical procedures and have a longer duration of action after dental surgery. Rofecoxib was found to provide superior analgesic effect compared with celecoxib, 200 mg. There were insufficient data to comment on toxicity.[Level of evidence: I]