Novel and Future Directions in Cancer Pain Management

Presence of pain is often the first sign of cancer; approximately 20% to 75% of patients present with pain at the time of diagnosis. Despite the availability of pharmacological treatments, the undertreatment of cancer pain is well documented. During the course of disease, 17% to 57% of patients experience moderate to severe pain, 25% to 40% of cancer survivors go on to experience chronic pain. At the 29th Annual Scientific Meeting of the American Pain Society, Christine Miaskowski, RN, PhD, FAAN, of the University of California at San Francisco, San Francisco, Calif., highlighted the importance of evaluating cancer pain etiologies as well as interindividual variability when managing cancer patients with pain. Patrick W. Mantyh, PhD, JD, of the University of Arizona, Tucson, Ariz., and Cielito C. Reyes-Gibby, DrPH, of the University of Texas MD Anderson Cancer Center, Houston, Texas, presented current data on the molecular, biochemical, and neurobiological mechanisms and the genetic determinants of cancer and metastatic cancer pain.

Originally published on MPR - Monthly Prescribing Reference.

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A new expert panel guideline on opioid rotation for the clinical management of cancer pain has been developed to address the issue of undertreatment of cancer pain. Opioid rotation opens the therapeutic window and creates an improved analgesia-toxicity relationship. By substituting opioids and using lower doses it is possible to reduce the incidence of side effects while increasing opioid responsiveness thus, improving analgesia. When converting to alternative opioids, Oscar de Leon-Casasola, MD, of the University of Buffalo School of Medicine and Biomedical Sciences, emphasized that a better understanding of the pharmacokinetic and pharmacodynamic relationships of opioids can optimize therapy.

Dose titration of opioids involves the consideration of several factors, including the route of metabolism and the presence of active metabolites and their pharmacokinetic and pharmacodynamic properties. Morphine and its metabolite M-6-G have synergistic effects after 21 days, thus if given over time improved analgesia with a lower incidence of side effects is observed. Whereas morphine and its derivatives (e.g., hydromorphone, oxymorphone) undergo glucuronidation, most opioids are metabolized by the CYP450 enzymes, primarily CYP3A4 and 2D6. Methadone is affected additionally by CYP2B6, 2C8, 2C9, and 2C19. When administering chemotherapeutic agents that use the CYP3A4 enzymes as substrates or other medications that induce or inhibit the CYP450 enzymes, Dr. de Leon-Casasola stressed the importance of being "mindful of considerable interaction potentials with opioids that may increase or reduce duration and degree of analgesia."

True breakthrough pain is characterized by moderate to severe intensity, rapid onset, relatively short duration, a frequency of 1 to 4 episodes per day, and is associated with more severe pain conditions. A widely accepted therapeutic proposal suggests that all breakthrough pain events are somatic in origin and should be treated with opioids.

Current pharmacotherapeutic trends include the use of adjuvant therapy, including tricyclic antidepressants, anticonvulsants and steroids, in conjunction with opioids. Selection of adjuvants should be based on side effect profiles and patient comorbidities. According to Dr. de Leon-Casasola, "a multi-therapy approach to developing treatment regimens may be implemented in patients with pain related to cancer with a high success rate of about 90% to 95%."

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