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The Pharmacologic Management of Cancer Pain

The Pharmacologic Management of Cancer Pain

The Pharmacologic Management of Cancer Pain" by Nathan Cherny is an excellent, comprehensive, yet concise paper on the treatment of cancer pain. It even goes beyond its stated intention of discussing pharmacologic treatment, as it ventures- in a very appropriate, balanced, and succinct manner-to delve into the issues of psychological therapies and physiatric and invasive analgesic techniques. This paper makes several very important points, and should be carefully read, understood, and assimilated. When correctly applied, many concepts, sometimes explained by a few words or a short sentence, can make a significant difference in prescribing a successful therapy. Interpretation of the WHO Ladder
The first important point made by the author presents the proper interpretation of the World Health Organization (WHO) "three-step analgesic ladder." Many health-care professionals have wrongly interpreted the WHO ladder to indicate that the first medications to be used to treat cancer pain are nonsteroidal anti-inflammatory drugs (NSAIDs) and adjuvant medications, independent of the severity of the presenting pain problem. Dr. Cherny clearly and correctly states that the appropriate analgesics to be prescribed are the ones that will properly treat the pain problem based mostly on its severity. Second, he raised the concern of using NSAIDs in patients at increased risk for adverse side effects. The pervasive opiophobia exhibited by many physicians is responsible for patients frequently being prescribed excessive yet ineffective doses of nonopioid medications with little regard for the possible, and sometimes very serious, side effects caused by high doses and protracted use of these medications. Pharmacology of Opioids
Two other very important points that Dr. Cherny makes are regarding the pharmacology of opioids. The first is the response to the dose of opioids administered. The analgesic response to an opioid is not linear; instead it must reach a "minimal effective analgesic concentration" (MEAC) in order to induce analgesia. This concentration is affected by the intensity of the pain and the genetic makeup of the patient. Until the MEAC is reached, very little change in the intensity of pain occurs. For this reason Dr. Cherny suggests increasing a noneffective dose of an opioid by 30% to 50% each time until proper analgesia is achieved. The second point that must be emphasized is the importance of the genetic makeup of each individual patient. This individual genetic variability greatly determines the dose response and possible intensity of the side effects caused by different opioids. This important concept, not appreciated by most physicians, currently precludes the use of standardized drugs and doses for every patient. Instead, it mandates tailoring the therapy to each individual patient need and response; in other words: individualization of therapy. Another important point made by Dr. Cherny is that very severe pain must be considered an emergency and be treated as such: rapidly and "...by repeated parenteral administration every 15 to 30 minutes until the pain is partially relieved." Equianalgesic Dose Ratio
The focus on equianalgesic dose ratio is very important, and the insertion of Table 2 can be very helpful for clinicians. While the table is similar to most published tables on equianalgesic doses, the conversion from continuous infusion of hydromorphone to continuous IV methadone is inaccurate. Manfredi et al[1] showed that IV methadone is approximately four to five times more powerful than IV hydromorphone. The use of the conversion ratio published in the various current tables has been responsible for at least one severe methadone overdose as far as this author is aware. The onset of respiratory depression seems to occur up to 10 hours after the IV dose of methadone. The initial titration of methadone either orally or IV should be done by clinicians who are experts in its use. Opioid Side Effects
Dr. Cherny has been very thorough in describing the side effects associated with chronic use of opioids and their symptomatic treatment. Recently, significant attention has been focused on the hypogonadism induced in many patients treated chronically with opioids. Some studies have focused on the effect of opioids on testosterone[2-5] and the resultant effect on the well-being of the patients; two studies have also shown that premenopausal women may develop either amenorrhea or an irregular menstrual cycle while on chronic opioid therapy.[4,5] Further studies are needed not only to evaluate the extent of the problem, but also to determine the need for systematic endocrine work-up and the necessity of supplemental endocrine therapy to improve the quality of life of pain patients treated with chronic opioid therapy. Conclusion
In conclusion, Dr. Cherny's article is excellent. In addition, its extensive bibliography allows for furthering one's knowledge on specific subjects related to pain therapy. It should be carefully read and assimilated by physicians treating patients suffering with cancer-related pain. Most concepts included in the article are also useful to all physicians who treat patients who suffer pain. The article clearly indicates the difficulties inherent in proper pain therapy. It is hoped that it will influence the curricula of oncology fellowships worldwide to include extensive clinical education about pain and symptom control, and that practicing oncologists will dedicate some time to being mentored on these topics at the bedside in order to develop at least some basic clinical knowledge of treating pain and symptoms associated with cancer.


The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.


1. Manfredi PL, Borsook D, Chandler SW, et al: Intravenous methadone for cancer pain unrelieved by morphine and hydromorphone: Clinical observations. Pain 70(1):99-101, 1997.
2. Daniell HW: Hypogonadism in men consuming sustained-action oral opioids. J Pain 3(5):377-384, 2002.
3. Rajagopal A, Vassilopoulou-Sellin R, Palmer JL, et al: Symptomatic hypogonadism in male survivors of cancer with chronic exposure to opioids. Cancer 100(4):851-858, 2004.
4. Abs R, Verhelst J, Maeyaert J, et al: Endocrine consequences of long-term intrathecal administration of opioids. J Clin Endocrinol Metab 85(6):2215-2222, 2000.
5. Finch PM, Roberts LJ, Price L, et al: Hypogonadism in patients treated with intrathecal morphine. Clin J Pain 16(3):251-254, 2000.
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