The Pharmacologic Management of Cancer Pain

October 1, 2004

The Pharmacologic Managementof Cancer Pain” by NathanCherny is an excellent, comprehensive,yet concise paper on thetreatment of cancer pain. It even goesbeyond its stated intention of discussingpharmacologic treatment, as it ventures-in a very appropriate, balanced,and succinct manner-to delve intothe issues of psychological therapiesand physiatric and invasive analgesictechniques.

The Pharmacologic Managementof Cancer Pain" by NathanCherny is an excellent, comprehensive,yet concise paper on thetreatment of cancer pain. It even goesbeyond its stated intention of discussingpharmacologic treatment, as it ventures-in a very appropriate, balanced,and succinct manner-to delve intothe issues of psychological therapiesand physiatric and invasive analgesictechniques.This paper makes several very importantpoints, and should be carefullyread, understood, and assimilated.When correctly applied, many concepts,sometimes explained by a fewwords or a short sentence, can make asignificant difference in prescribing asuccessful therapy.Interpretation ofthe WHO Ladder
The first important point made bythe author presents the proper interpretationof the World Health Organization(WHO) "three-step analgesicladder." Many health-care professionalshave wrongly interpreted the WHOladder to indicate that the first medicationsto be used to treat cancer painare nonsteroidal anti-inflammatorydrugs (NSAIDs) and adjuvant medications,independent of the severityof the presenting pain problem. Dr.Cherny clearly and correctly statesthat the appropriate analgesics to beprescribed are the ones that will properlytreat the pain problem based mostlyon its severity.Second, he raised the concern ofusing NSAIDs in patients at increasedrisk for adverse side effects. The pervasiveopiophobia exhibited by manyphysicians is responsible for patientsfrequently being prescribed excessiveyet ineffective doses of nonopioidmedications with little regard for thepossible, and sometimes very serious,side effects caused by high doses andprotracted use of these medications.Pharmacology of Opioids
Two other very important pointsthat Dr. Cherny makes are regardingthe pharmacology of opioids. The firstis the response to the dose of opioidsadministered. The analgesic responseto an opioid is not linear; instead itmust reach a "minimal effective analgesicconcentration" (MEAC) in orderto induce analgesia. Thisconcentration is affected by the intensityof the pain and the genetic makeupof the patient. Until the MEAC isreached, very little change in the intensityof pain occurs. For this reasonDr. Cherny suggests increasing a noneffectivedose of an opioid by 30% to50% each time until proper analgesiais achieved.The second point that must be emphasizedis the importance of the geneticmakeup of each individualpatient. This individual genetic variabilitygreatly determines the dose responseand possible intensity of theside effects caused by different opioids.This important concept, not appreciatedby most physicians,currently precludes the use of standardizeddrugs and doses for everypatient. Instead, it mandates tailoringthe therapy to each individual patientneed and response; in other words:individualization of therapy.Another important point made byDr. Cherny is that very severe painmust be considered an emergency andbe treated as such: rapidly and "...byrepeated parenteral administration every15 to 30 minutes until the pain ispartially relieved."Equianalgesic Dose Ratio
The focus on equianalgesic doseratio is very important, and the insertionof Table 2 can be very helpful forclinicians. While the table is similarto most published tables on equianalgesicdoses, the conversion from continuousinfusion of hydromorphoneto continuous IV methadone is inaccurate.Manfredi et al[1] showed thatIV methadone is approximately fourto five times more powerful than IVhydromorphone. The use of the conversionratio published in the variouscurrent tables has been responsiblefor at least one severe methadone overdoseas far as this author is aware.The onset of respiratory depressionseems to occur up to 10 hours afterthe IV dose of methadone. The initialtitration of methadone either orally orIV should be done by clinicians whoare experts in its use.Opioid Side Effects
Dr. Cherny has been very thoroughin describing the side effectsassociated with chronic use of opioidsand their symptomatic treatment.Recently, significant attention hasbeen focused on the hypogonadisminduced in many patients treatedchronically with opioids. Some studieshave focused on the effect of opioidson testosterone[2-5] and theresultant effect on the well-being ofthe patients; two studies have alsoshown that premenopausal womenmay develop either amenorrhea or anirregular menstrual cycle while onchronic opioid therapy.[4,5] Furtherstudies are needed not only to evaluatethe extent of the problem, but alsoto determine the need for systematicendocrine work-up and the necessityof supplemental endocrine therapy toimprove the quality of life of painpatients treated with chronic opioidtherapy.Conclusion
In conclusion, Dr. Cherny's articleis excellent. In addition, its extensivebibliography allows for furtheringone's knowledge on specific subjectsrelated to pain therapy. It should becarefully read and assimilated by physicianstreating patients suffering withcancer-related pain. Most conceptsincluded in the article are also usefulto all physicians who treat patientswho suffer pain. The article clearlyindicates the difficulties inherent inproper pain therapy. It is hoped that itwill influence the curricula of oncologyfellowships worldwide to includeextensive clinical education about painand symptom control, and that practicingoncologists will dedicate sometime to being mentored on these topicsat the bedside in order to developat least some basic clinical knowledgeof treating pain and symptomsassociated with cancer.

Disclosures:

The author has no significantfinancial interest or other relationshipwith the manufacturers of any productsor providers of any service mentioned in thisarticle.

References:

1.

Manfredi PL, Borsook D, Chandler SW,et al: Intravenous methadone for cancer painunrelieved by morphine and hydromorphone:Clinical observations. Pain 70(1):99-101, 1997.

2.

Daniell HW: Hypogonadism in men consumingsustained-action oral opioids. J Pain3(5):377-384, 2002.

3.

Rajagopal A, Vassilopoulou-Sellin R,Palmer JL, et al: Symptomatic hypogonadismin male survivors of cancer with chronic exposureto opioids. Cancer 100(4):851-858, 2004.

4.

Abs R, Verhelst J, Maeyaert J, et al: Endocrineconsequences of long-term intrathecaladministration of opioids. J Clin EndocrinolMetab 85(6):2215-2222, 2000.

5.

Finch PM, Roberts LJ, Price L, et al: Hypogonadismin patients treated with intrathecalmorphine. Clin J Pain 16(3):251-254, 2000.