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Summary An expert working group of the European Association for Palliative Care has revised and updated its guidelines on the use of morphine in the management of cancer pain. The revised recommendations presented here give guidance on the use of morphine and the alternative strong opioid analgesics which have been introduced in many parts of the world in recent years. Practical strategies for dealing with difficult situations are described presenting a consensus view where supporting evidence is lacking. The strength of the evidence on which each recommendation is based is indicated. http://www.bjcancer.com Daytime drowsiness, dizziness or mental clouding commonly occur at the start of treatment but resolve when patients are stabilized (usually within a few days). For most patients receiving stable doses of morphine effects on cognitive and psychomotor function are minimal. In particular, there are data indicating that patients' driving ability is not significantly impaired, in alert patients receiving a stable dose (Vainio et al, 1995). Similarly, nausea and vomiting, which occur in up to two-thirds of patients when morphine is started, usually resolve. The main continuing adverse effect from morphine is constipation, and the prophylactic use of a laxative is almost always required. Morphine: limitationsThe systemic availability of morphine by the oral route is poor (20-30%) and this contributes to a sometimes unpredictable onset of action and great interindividual variability in dose requirements and response (Glare and Walsh, 1991). Active metabolites may contribute to toxicity, particularly in patients with renal impairment (McQuay and Moore, 1997). And some types of pain do not always respond well or completely to morphine, notably neuropathic pain. However, none of the alternatives to morphine has so far demonstrated advantages which would make it preferable as the first line oral opioid for cancer pain. Morphine remains our first choice but for reasons of familiarity, availability and cost rather than proven superiority.2. The optimal route of administration of morphine is by mouth. Ideally, two types of formulation are required: normal release (for dose titration) and modified release (for maintenance treatment) CThe oral route is the simplest and most acceptable to patients.There is large interindividual variation in kinetics (Säwe, 1986) and dynamics in cancer patients whose pain will also vary in severity so that the dose must be titrated against effect for each patient, and the starting dose will be determined by previous analgesic treatment. Patients changing from regular administration of a step 2 opioid (in combination with a non-opioid) will usually start with 10 mg every 4 hours. If step 2 of the analgesic ladder is omitted 5 mg every 4 hours may suffice, whereas patients converted from another step 3 opioid will require more. During dose titration it is preferable to use a formulation of morphine that has a rapid onset and a short duration of action to allow steady state to be achieved as quic...

Successful pain management with opioids requires that adequate analgesia be achieved without excessive adverse effects. By these criteria, a substantial minority of patients treated with oral morphine (10% to 30%) do not have a successful outcome because of (1) excessive adverse effects, (2) inadequate analgesia, or (3) a combination of both excessive adverse effects along with inadequate analgesia. The management of excessive adverse effects remains a major clinical challenge. Multiple approaches have been described to address this problem. The clinical challenge of selecting the best option is enhanced by the lack of definitive, evidence-based comparative data. Indeed, this aspect of opioid therapeutics has become a focus of substantial controversy. This study presents evidence-based recommendations for clinical-practice formulated by an Expert Working Group of the European Association of Palliative Care (EAPC) Research NETWORK: These recommendations highlight the need for careful evaluation to distinguish between morphine adverse effects from comorbidity, dehydration, or drug interactions, and initial consideration of dose reduction (possibly by the addition of a co analgesic). If side effects persist, the clinician should consider options of symptomatic management of the adverse effect, opioid rotation, or switching route of systemic administration. The approaches are described and guidelines are provided to aid in selecting between therapeutic options.

Highlights This ESMO Clinical Practice Guideline provides key recommendations for managing cancer-related cachexia. It covers screening, assessment and multimodal management of cancer cachexia. All recommendations were compiled by a multidisciplinary group of experts. Recommendations are based on available scientific data and the author's expert opinion.

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