• Sebastiano Mercadante, Gianpiero Porzio, Patrizia Ferrera, Fabio Fulfaro, Federica Aielli, Corrado Ficorella, Lucilla Verna, Walter Tirelli, Patrizia Villari, and Edoardo Arcuri.
• Anesthesia & Intensive Care Unit, La Maddalena Clinic for Cancer, and Department of Anesthesiology and Intensive Care, University of Palermo, Palermo, Italy. terapiadeldolore@la.maddalena.it
• J Pain Symptom Manage. 2006 Mar 1;31(3):242-7.

AbstractCancer pain can be managed in most patients through the use of the analgesic ladder proposed by the World Health Organization. Recent studies have proposed to skip the second "rung" of the ladder by using a so-called "strong" opioid for moderate pain. However, usual doses of strong opioids commonly prescribed for the third rung of the analgesic ladder may pose several problems in terms of tolerability in opioid-naive patients. The aim of this multicenter study was to evaluate the efficacy and tolerability of very low doses of morphine in advanced cancer patients no longer responsive to nonopioid analgesics. A sample of 110 consecutive opioid-naive patients with moderate-to-severe pain were given oral morphine at a starting dose of 15 mg/day (10 mg in those older than 70 years). Doses were then titrated according to the clinical situation. Pain intensity, morphine doses, symptom intensity, quality of life, and the requirement for dose escalation were monitored for a period of 4 weeks. The treatment was effective and well tolerated by most patients, who were able to maintain relatively low doses for the subsequent weeks (mean dose 45 mg at Week 4). Only 12 patients dropped out due to poor response or other reasons. The use of very low doses of morphine proved to be a reliable method in titrating opioid-naive advanced cancer patients who were also able to maintain their dose, in a 4-week period, below the dose level commonly used when prescribing strong opioids.

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