The presence of bone metastases predicts the presence of pain and is the most common cause of cancer-related pain. Although bone metastases do not involve vital organs, they may determine deleterious effects in patients with prolonged survival. Bone fractures, hypercalcaemia, neurologic deficits and reduced activity associated with bone metastases result in an overall compromise in the patient's quality of life. A metastasis is a consequence of a cascade of events including a progressive growth at the primary site, vascularization phase, invasion, detachment, embolization, survival in the circulation, arrest at the site of a metastasis, extravasion, evasion of host defense and progressive growth. Once cancer cells establish in the bone, the normal process of bone turnover is disturbed. The different mechanisms responsible for osteoclast activation correspond to typical radiologic features showing lytic, sclerotic or mixed metastases, according to the primary tumor. The release of chemical mediators, the increased pressure within the bone, microfractures, the stretching of periosteum, reactive muscle spasm, nerve root infiltration and compression of nerves by the collapse of vertebrae are the possible mechanisms of malignant bone pain. Pain is often disproportionate to the size or degree of bone involvement. A comprehensive assessment including a trusting relationship with the patient, taking a careful history of the pain complaint, the characteristics of the pain, the evaluation of the psychological status of the patient, neurological examination, the reviewing of diagnostic studies and laboratory findings, and individualization of the therapeutic approach, should precede any treatment. Radiotherapy is the cornerstone of the treatment. Low doses given in a single session are safe and effective, and reduce distress and inconvenience associated with repeated session. Radioisotopes are more imprecise in delivering specific doses of radiation, but have less toxicity and easy administration as well as effectiveness in subclinical sites of metastases, although storage, dispensing and administration should be under strict control. Chemotherapy and endocrine therapy are difficult to measure in terms of pain relief. Prophylactic fixation surgery can lead to improved survival and quality of life of patients with bone metastases. Surgical treatment should be undertaken when fracture occurs. Careful selection of patients for surgical spinal decompression is required. The potential benefits of surgical interventions have to be tempered with patient survival. The use of analgesics according to the WHO ladder is recommended. There is no clear evidence that non-steroidal anti-inflammatory drugs (NSAIDs) have a specific efficacy in malignant bone pain. The difficulty with incident pain is not a lack of response to systemic opioids, but rather that the doses required to control the incidental pain produce unacceptable side-effects at rest. Alternative measures are often required. The inhibition of bone resorption and hypercalcaemi...

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...

Four hundred consecutive patients who were referred to a home palliative care program were prospectively surveyed to estimate the prevalence and severity of common symptoms according to the changes in the performance status. Patients were admitted for the presence of different symptoms and psychosocial support. Common symptoms included in a standard form were rated for severity (absent 0, mild 1, moderate 2, severe 3) for each visit. Pain intensity was rated on a numerical scale (0-10). For each level of Karnofsky performance score (K), the frequency and the worse symptom intensity were recorded until patient's death. Data from 370 patients were analyzed. Pain was effectively controlled. In the final stage, it was also less frequently observed, despite the use of lower analgesic doses in the last days of life. The peak of opioid consumption and symptom frequency and severity was found at K40. This was also the most frequent K level at admission. Some symptoms, such as nausea and vomiting, dry mouth, gastric pyrosis, and diarrhea reached a peak in frequency and severity, then decreased with the advanced stage of the disease. Other symptoms, such as dyspnea, drowsiness, weakness, and confusion tended to further increase and to have a peak at the lowest levels of K. Dysphagia and constipation progressively increased in frequency and intensity, but decreased at the end. These findings clarify the actual frequency and intensity of symptoms in a non-selected home care population with advanced cancer.

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In this paper we describe the results of a systematic search of the literature on conversion ratios during opioid switching. This is part of a project of the European Palliative Care Research Collaboration to update the European Association for Palliative Care recommendations for the use of opioid analgesics in the treatment of cancer pain. Studies were eligible for inclusion if they involved adult patients with chronic cancer pain, contained data on opioid conversion ratios, were prospective and were written in English. Thirty-one studies were identified and included. The majority of the studies had methodological flaws and were not designed to explore or demonstrate equianalgesic dose data. However, the data allow some recommendations to be made that could be helpful to clinicians for whom there are few reliable experimental data on which to base dosing guidelines. Switching to transdermal fentanyl (TDfe) or buprenorphine (TDbu) is an option for patients with stable, controlled pain. Reliable and consistent studies show a ratio of 100 : 1 between oral morphine (ORmo) and TDfe. A ratio of 75 : 1 between ORmo and TDbu may be appropriate, but the supporting evidence here is much less robust. Data are relatively consistent to support a conversion ratio between ORmo and oral hydromorphone (ORhy) of 5 : 1. Despite some limitations, there is evidence to support the use of an approximate conversion ratio of ORmo:oral oxycodone (ORox) of 1.5 : 1. The conversion between ORox and ORhy is estimated to be 1 : 4. When switching from different opioids to methadone the conversion ratio is highly variable, ranging from 5 : 1 to 10 : 1 and much higher in some studies. The derived ratios are influenced by several factors, including the reasons for switching and previous opioid doses. An individual treatment decision and strict monitoring is recommended for patients considered at risk.

In this open-label, randomised, crossover trial, significantly more patients attained faster 'meaningful' pain relief with INFS than OTFC, and more patients preferred INFS to OTFC.

In light of the results obtained in the study, the extensive use of the drug for cancer pain should be questioned.

According to new preclinical data, treatment of bone cancer pain requires multidisciplinary therapies such as radiotherapy applied to the painful area along with systemic treatment (hormone therapy or chemotherapy) and supportive care (analgesic therapy and bisphosphonates). In some selected cases use of radioisotopes and other noninvasive or minimally invasive techniques may be useful in the management of metastatic bone pain. The treatment should be individualized according to the patient's clinical condition, life expectancy, and quality of life.