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Conrad Notes
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F. De Conno, MD, National Cancer Institute, Milan, Italy, advocates integrating palliative care with curative treatment early in managing the cancer patient. Morphine, methadone, and other strong analgesics provide relief of severe pain. Rectal morphine merits consideration when oral dosing is not possible.

The World Health Organization (WHO) analgesic ladder In 1983, WHO devised an approach to assure a rational titration in treating cancer pain. Step 1 specifies a non-opioid for mild pain. Step 2 adds a weak opioid such as codeine, tramadol, or buprenorphine for moderate pain. Step 3 requires a strong opioid including morphine, methadone, fentanyl, and others to control severe cancer pain. An estimated 80% to 90% of patients treated in this manner achieve pain relief, according to WHO.

Oral morphine vs methadone The Milan group conducted an open, comparative study in 54 cancer pain patients randomized to receive oral methadone or morphine for 14 days (J Pain Sympt Manag 1986;1:203-207). Comparable mean peak pain scores persisted for both treatment groups during the 14 days. The initial average dose of methadone proved adequate for the duration of study. The morphine starting dose of 73 mg had to be increased to 119 mg to assure pain control. Side effects were similar except for dry mouth and headache. Dry mouth occurred more frequently with morphine and headache more often with methadone.

Retrospective evaluation of liquid methadone in 196 patients De Conno showed oral methadone, given every 8 hours, produced satisfactory analgesia in patients with advanced cancer- related pain (J Clin Oncol 1996;14:2836-2842). Duration of treatment ranged from 7 to 90 days with a mean dose of 14 mg on Day 7 and 24 mg on Day 90. Some 11% of the patients withdrew from the study due to inadequate analgesia and 7% because of methadone-related drowsiness (10 patients) or severe constipation (3 patients).

Rectal vs oral morphine According to the Expert Group of the European Association for Palliative Care, morphine remains the preferred strong opioid analgesic (BMJ 1996;312:823-826). Oral administration continues to be the desired route; however, rectal dosing is indicated in patients with dysphagia, nausea and uncontrolled vomiting, bowel obstruction, cognitive failure, and coma.

In De Conno's study, 34 opioid-naive cancer patients with pain participated under double-blind, double-dummy, crossover conditions (J Clin Oncol 1995;13:1004-1008). Each patient received a daily dose of 10 mg oral morphine hydrochloride in orange juice or the same dose as a microenema for each two-day treatment period. Symptom assessment of pain, nausea and sedation followed up to 6 hours after each dose.

At 10 minutes post dosing, rectal morphine led to significant pain relief (p<0.03). Oral morphine required an additional 50 minutes to show a significant decrease in pain intensity (p<0.01). At 180 minutes post dosing, pain intensity continued to be significantly lower than at baseline after rectal dosing but not after oral administration. In De Conno's opinion, rectal liquid morphine is safe, effective, easy to manage, inexpensive, and rapid in onset.

Beyond morphine and methadone De Conno recommends using morphine first for severe cancer pain before switching to transdermal fentanyl (TF), if needed. The transfer of a TF-unresponsive patient to another opioid requires using an overlapping analgesic to prevent breakthrough pain.

The review of Mercadante presents ketamine as a promising option in treating cancer pain (Pall Med 1996;10:225-230). This agent inhibits N-methyl-D-aspartate (NMDA) receptors to provide pain relief by various routes of administration. Ketamine shows synergism when combined with morphine in patients unresponsive to high doses of intravenous morphine. For example, subcutaneous infusion of ketamine with a reduced dose of morphine is effective in neuropathic pain.

Another strong drug meriting consideration is pamidronate. In one study, 60 mg of intravenous pamidronate relieved pain of movement due to metastatic bone cancer and improved quality of life (Br J Cancer 1994;70:554).

Effect of cancer pain on life's quality De Conno believes that the psychological, social and spiritual effects of cancer pain need recognition and improved management. Palliative care focuses on treating the patient and not just the disease. The palliative care physician and oncologist ought to collaborate in resolving the patient's problems. The WHO objectives on palliative care can only be met by educators concentrating on programs for medical students and not for teachers, in De Conno's opinion.

For professional correspondence, contact Dr. De Conno by E-mail at: tdpint@mbox.vol.it

Eugene A. Conrad

Presented at The European Cancer Conference (ECCO 9), September 14-18, 1997
Copyright © 1997 Conrad Group, Inc. All Rights Reserved
Eugene A. Conrad, PhD, MPH / ISSN 1078-2230 / November 1997
Send comments to: ConradNote@aol.com

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