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This paper reports on the experience gained using World Health Organization Guidelines for cancer pain relief over a 10-year period in an anaesthesiology-based pain service associated with a palliative care programme. The course of treatment of 2118 patients was assessed prospectively over a period of 140,478 treatment days. Non-opioid analgesics (WHO step I) were used on 11%, weak opioids (WHO step II) on 31% and strong opioids (WHO step III) on 49% of treatment days. Administration was via the enteral route on 82% and parenterally on 9% of treatment days. On the remaining days, either spinally applied opioids (2%) or other treatments (6%) were utilised. Fifty-six percent of the patients were treated with morphine. Morphine dose escalation was observed in about one-half of the patients being cared for until death, whereas the other half had stable or decreasing doses over the course of treatment. Co-analgesics were administered on 37% of days, most often antidepressants (15%), anticonvulsants (13%) and corticosteroids (13%). Adjuvants to treat symptoms other than pain were prescribed on 79% of days, most commonly laxatives (42%), histamine-2-receptor antagonists (39%) and antiemetics (35%). In addition, palliative antineoplastic treatment was performed in 42%, nerve blocks in 8%, physiotherapy in 5%, psychotherapy in 3% and TENS in 3% of patients. A highly significant pain reduction was achieved within the 1st week of treatment (P < 0.001). Over the whole treatment period, good pain relief was reported in 76%, satisfactory efficacy in 12% and inadequate efficacy in 12% of patients. In the final days of life, 84% rated their pain as moderate or less, while 10% were unable to give a rating. Analgesics remained constantly effective in all 3 steps of the WHO ladder. Other clinical symptoms were likewise significantly reduced at 1 week after initial assessment, with the exception of neuropsychiatric symptoms. During the course of treatment, the latter were the major symptoms on 23% of days, followed by nausea (23%), constipation (23%) and anorexia (20%). Our results emphasise once again the marked efficacy and low rate of complications associated with oral and parenteral analgesic therapy as the mainstay of pain treatment in the palliative care of patients with advanced cancer. Wide dissemination of WHO guidelines among doctors and healthcare workers is thus necessary to effect a clear improvement in the treatment of the many patients suffering from cancer pain in the clinical and home setting.
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PMID:Validation of World Health Organization Guidelines for cancer pain relief: a 10-year prospective study. 857 92

The dose ratio, analgesic efficacy, toxicity and cost of methadone for cancer pain were evaluated in a retrospective review of 50 consecutive patients treated on a Palliative Care Unit. Patients were switched from hydromorphone 267.7 +/- 178.8 mg sc per day to custom-made capsules (24) or suppositories (26) of methadone for reasons of uncontrolled pain (24), toxicity (8), both (15) or other (2). The change in opioid occurred over 2.5 +/- 3.6 days, with another 4.4 +/- 3.7 days required to reach stable methadone dose. The ratio of stable methadone dose to final hydromorphone dose was 1.07 +/- 0.9 (oral) and 1.88 +/- 1.27 (rectal) (p = 0.01). Visual analogue scores for pain intensity (0-100 mm) declined from 50.8 +/- 22 to 40 +/- 20 (p = 0.01). The most frequent toxicities were constipation (46), sedation (42) and nausea (18). Six patients developed respiratory depression. Total cost of treatment was Canadian $116.77 +/- 157.17 for methadone capsules and Canadian $105.34 +/- 146.35 for methadone suppositories, vs Canadian $3450.51 +/- 5098.58 (p = 0.0001) for hydromorphone parenteral solution and Canadian $1801.21 +/- 2661.52 (p = 0.0001) for hydromorphone powder. It is concluded that methadone is an effective and inexpensive alternative in patients receiving high-dose opioids for cancer pain, at dose ratios much lower than recommended in the literature. The incidence of serious toxicities suggests that methadone should only be initiated in an adequately monitored setting by pain management experts.
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PMID:Capsules and suppositories of methadone for patients on high-dose opioids for cancer pain: clinical and economic considerations. 862 39

Few controlled clinical trials of psychological interventions for cancer pain relief exist in spite of frequent support for their importance as adjuncts to medical treatment. This study compared oral mucositis pain levels in 4 groups of cancer patients receiving bone marrow transplants (BMT): (1) treatment as usual control, (2) therapist support, (3) relaxation and imagery training, and (4) training in a package of cognitive-behavioral coping skills which included relaxation and imagery. A total of 94 patients completed the study which involved two training sessions prior to treatment and twice a week 'booster' sessions during the first 5 weeks of treatment. Results confirmed our hypothesis that patients who received either relaxation and imagery alone or patients who received the package of cognitive-behavioral coping skills would report less pain than patients in the other 2 groups. The hypothesis that the cognitive-behavioral skills package would have an additive effect beyond relaxation and imagery alone was not confirmed. Average visual analogue scale (VAS) report of pain within the therapist support group was not significantly lower than the control group (P = 0.103) nor significantly higher than the training groups. Patient reports of relative helpfulness of the interventions for managing pain and nausea matched the results of VAS reports. From these results, we conclude that relaxation and imagery training reduces cancer treatment-related pain; adding cognitive-behavioral skills to the relaxation with imagery does not, on average, further improve pain relief.
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PMID:Relaxation and imagery and cognitive-behavioral training reduce pain during cancer treatment: a controlled clinical trial. 862 84

This case report describes a patient affected by a neuropathic pain syndrome, which was secondary to a renal cell carcinoma metastatic to the spine, and complicated by incidental components and somatization. Due to a rapid development of tolerance and toxicity from hydromorphone, a rotation to methadone was made, with a decrease of the morphine equivalent daily dose (MEDD) from 1050 to 36. After 4 mos of good pain relief, a switch over back to hydromorphone was necessary due to worsening pain, associated with myoclonus and sedation secondary to methadone; the MEDD this time escalated from 480 to 4950. The use of hydromorphone was complicated by the onset of intractable nausea and sedation. After 2 wks, the patient was rotated again to methadone, with a decrease of the MEDD to 24. He achieved good pain control and was free of opioid toxicity. Our findings illustrate a role of methadone in the management of cancer pain associated with poor prognostic indicators, the development of tolerance towards its effects, and the regaining of sensitivity to methadone, by temporary rotation to another opioid. Possible mechanism for opioid tolerance and its reversal are discussed.
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PMID:Individualized use of methadone and opioid rotation in the comprehensive management of cancer pain associated with poor prognostic indicators. 889 38

We reported the kind of symptoms and how they could be palliated in terminally ill patients at home based on our experience of about 9 years. Cancer pain, which was the most frequent symptom, appeared in 67 among 126 patients receiving home care, and it could be effectively controlled with morphine; no patient returned to the hospital because of aggravation of pain. Very few patients stayed in the hospital and never returned home due to uncontrollable pain. Home parenteral infusion was done for 63 patients who were unable to eat or drink because of peritonitis carcinomatosa or cancer cachexia. High fever in the tumor mass was controlled by glucocorticoid hormone, and ascites was drained continuously when the patients suffered from abdominal distension. From analysis of the cases in which home care was interrupted or those in which patients were unable to transfer to home care, symptoms that were difficult to palliate at home were nausea caused by bowel obstruction, acute symptoms (bleeding, disturbance of consciousness, and so on), and dyspnea. But if the patients and family are eager for home care and an adequate medical support system is in place, home care may be possible despite these symptoms.
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PMID:[How to palliate the symptoms of terminally ill patients at home]. 898 19

Fentanyl is a synthetic opioid with short-acting analgesic activity after intravenous or subcutaneous administration. The low molecular weight, high potency and lipid solubility of fentanyl make it suitable for delivery via the transdermal therapeutic system (TTS). These systems are designed to release the drug into the skin at a constant rate ranging from 25 to 100 micrograms/h, multiple systems can be applied to achieve higher delivery rates. Initially, much of the clinical experience with fentanyl TTS was obtained in patients with acute postoperative pain. However, because of the increased risk of respiratory complications, fentanyl TTS is contraindicated in this setting. Fentanyl TTS is recommended for use in chronic cancer pain. Moreover, in 11 countries worldwide including the US, its use is not restricted to chronic cancer pain; the drug is also available for treatment of general chronic pain, including that of nonmalignant origin. At the start of fentanyl TTS treatment, depot accumulation of the drug within skin tissue results in a significant delay (17 to 48 hours) before maximum plasma concentration is achieved. Approximately half of the cancer patients converted to transdermal fentanyl from other opioid agents required increased dosages after initial application of the patch. However, concomitant use of short-acting morphine maintained pain relief during the titration period, and the use of such supplementary medication decreased with the duration of fentanyl TTS treatment. In patients with chronic cancer pain, changes in visual analogue scale (VAS) pain scores ranged from a 10% increase (worse pain) to > 50% decrease (less pain) during transdermal fentanyl therapy compared with previous opioid treatment. In addition, patient preference for fentanyl TTS was indicated by the number of patient requests (up to 95%) for continued use of the drug at the end of the study. Although fentanyl TTS is contraindicated in patients postoperatively, the efficacy of fentanyl via the transdermal route was investigated in this patient group. Supplementary patient controlled analgesia was significantly reduced in patients who received fentanyl TTS 75 micrograms/h compared with placebo, although this was not apparent until > or = 12 hours after application. Data evaluating pain relief, which was assessed by VAS pain scores, were inconclusive. Preliminary data, although from relatively small numbers of patients, indicate that transdermal fentanyl may be useful in the management of chronic non-malignant pain. Indeed, some patients whose pain was previously uncontrolled became completely pain free. The most frequently occurring adverse events during fentanyl TTS therapy (as with other opioid agents) included vomiting, nausea and constipation, although vomiting and nausea were not clearly associated with the drug. The most serious adverse event was hypoventilation, which occurred more frequently in postoperative (4%) than in cancer patients (2%). In surgical patients, fentanyl-associated respiratory events (reduced respiratory rate and apnoea) generally occurred within 24 hours of patch application; however, there were isolated reports of late onset (> or = 36 hours postsurgery) fentanyl-associated respiratory depression. In cancer patients, the incidence of constipation was reduced by up to two-thirds after switching from oral morphine to transdermal fentanyl. Transient skin irritation associated with the plastic patch or the adhesive, rather than the drug, was reported in a maximum 3% of patients. In summary, transdermal fentanyl is a useful alternative to other opioid agents, which are also recommended on the third step of the WHO analgesic ladder, in the management of chronic malignant pain. Preliminary data indicate that it may be useful in the management of chronic nonmalignant pain. The advantages offered by fentanyl TTS over traditional methods of chronic pain control include its ease of administration, less constipation and the 3-
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PMID:Transdermal fentanyl. A review of its pharmacological properties and therapeutic efficacy in pain control. 901 Jun 52

Pain is the main reason prompting patients to consult their physicians. In acute conditions, pain has a very particular significance as a warning sign, enabling the physician to attempt a diagnosis. Nevertheless, its detrimental effect upon the individual (even in the case of acute pain) and its cost to society are now widely acknowledged. There can be no doubt about the physical component of pain, but the psychological and social aspects should not be ignored, particularly in the case of chronic pain. There is no single therapeutic approach to pain and, more often than not, successful treatment comprises a combination of several. Pharmacological treatments are undeniably the most common approach. In clinical practice, recent advances have been based upon an improved understanding of 'old' substances such as morphine and, at the same time, research continues in the hope of finding the 'ideal' analgesic-effective in most situations but without adverse effects: this appears to be a somewhat utopian arm at present, considering the number of different causes of pain. An improved understanding of the physiological mechanisms of pain has led, within the field of clinical practice, to several methods of differentiating pain. These depend on whether or not pain responds to morphine, or on the type of pain: pain due to an excess of nociception, pain resulting from deafferentation (caused by damage to nerve pathways) in the central or peripheral nervous system and psychogenic (idiopathic) pain. Likewise, there are several different ways of classifying analgesic treatments: according to the intensity of pain, as with use of the WHO ladder (which is based on the notion of steps) for the treatment of cancer pain; according to the presumed physiopathological mechanism and, in particular, the response to morphine, and according to the presumed central or peripheral mechanism of the drugs. In reality, peripherally acting drugs can also have a central mechanism of action, just as drugs known to have a central mechanism of action can also have peripheral activity. As a result, several therapeutic classes have been identified. Firstly NSAIDs, which act by inhibiting the enzymes that synthesise prostaglandins, cyclooxygenases (COX-1, COX-2), but which also act upon lipo-oxygenases: Their efficacy is interesting, although somewhat limited by both their ceiling effect and the frequent adverse gastrointestinal reactions they produce. Specific inhibitors of COX-2 could well reduce the risk of adverse effects. Opioids constitute the first-line treatment for pain, particularly severe pain. There are several classifications for these drugs. Firstly, weak opioids (such as codeine) and strong opioids (such as morphine) are differentiated. Secondly, a distinction is made between pure agonists (such as morphine), partial agonists (such as buprenorphine), agonist-antagonists (such as nalbuphine) and antagonists (such as naloxone). Finally, agents are distinguished on the basis of their chemical structure (synthetic, semi-synthetic or natural derivatives). These molecules act upon different receptors (mu, delta, kappa, sigma) and, although peripheral mechanisms have been described, their activity occurs mainly at spinal and supraspinal levels. They provide a potent analgesic effect but are also responsible for various adverse effects-nausea, vomiting, sedation, constipation and respiratory depression-which seriously limit their use. As long as the indication is appropriate, these drugs should not be withheld because of fear of dependence or abuse. It has been observed that other adjuvant therapeutic approaches, generally used to treat conditions other than pain, provide pain relief in certain situations. These include corticosteroids, which are-widely used in rheumatology and oncology, and antidepressants, which are frequently used to treat chronic pain, especially that with a neuropathic component. Anti-epileptics are also used, particularly for excrutiating
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PMID:[Review of current pharmacologic treatment of pain]. 919 Mar 20

Basic guidelines for cancer pain treatment can be found in many different handbooks published in the last years. Particularly those of the World Health Organisation published in 1986 and revised in 1996, furnish useful indication for cancer pain treatment. The authors therefore focused on resuming the most recent development in this field. In the research regarding alternative routes of administration of opioids in alternative to the oral route, the rectal administration of morphine and methadone and the transdermal route for fentanyl have proved to be efficacious. The subcutaneous route (for morphine) as well as the intravenous, peridural and subaracnoid routes, being known for some time are not taken in consideration in this paper. Various studies suggest that alternative routes are necessary in 53-70% of patients in their last days or months of live. The most frequent causes for the need to stop oral administration are dysphagia, nausea, and uncontrollable vomiting, bowel obstruction, malabsorption, cognitive failure, coma, and pain syndromes requiring anaesthetics which need be administered via the spinal route. Among the drugs, tramadol seems to be effective in the control of moderate pain. Tramadol is a centrally acting analgesic drug; it has an agonist effect on mu 1 receptors of opioids and acts also by inhibiting the re-uptake of noradrenaline and serotonine which activates descending monoaminergic inhibitory pathways. Recent clinical studies revealed that pamidronate has an analgesic effect in pain due to bone metastasis. Pamidronate is part of the biphosphonates, which are active on bone metabolism and are usually being used for the treatment of hypercalcaemia in cancer. The authors also describe briefly the indication of ketamin in association with morphine for the treatment of neuropathic pain.
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PMID:[Treatment of pain in oncology]. 923 25

Although the oral route is the preferred method of opioid therapy in patients with cancer pain, many patients will require an alternate route of analgesic administration at some point during the trajectory of their illness. This study compared the efficacy and safety of a novel, controlled-release suppository of morphine (MSC-R) and controlled-release morphine tablets (MSC-T) in patients with cancer pain. In a double-blind crossover study, 27 patients with cancer pain were randomized to receive MSC-R or MSC-T every 12 hours for 7 days each, using a 1:1 analgesic equivalence ratio. Pain intensity was assessed using a visual analog scale (VAS) and the Present Pain Intensity Index of the McGill Pain Questionnaire. Nausea and sedation were also assessed with a VAS. Pharmacodynamic assessments were made by the patient at 8:00 AM, 12:00 PM, 4:00 PM, and 8:00 PM and rescue morphine use recorded in a daily diary. There were no significant differences between MSC-R and MSC-T in overall scores for pain intensity VAS, ordinal pain intensity, and sedation. There was a small but significant difference in overall nausea VAS score in favor of MSC-R. Mean daily rescue analgesic use did not differ significantly during between treatment with MSC-R and MSC-T. MSC-R provides pain control comparable to that provided by MSC-T when given every 12 hours at a 1:1 dose ratio, and represents a reliable alternative method of pain control for patients unable to take oral opioid agents.
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PMID:Comparative efficacy and safety of controlled-release morphine suppositories and tablets in cancer pain. 959 63

Inadequate training of physicians contributes to the undertreatment of cancer pain. To address these concerns, the University of Kentucky has introduced a 4-week course for final-year medical students that teaches the principles of clinical pharmacology and pain management. The purposes of this study are to assess the knowledge deficits of final-year medical students about the use of morphine for cancer pain and to assess the efficacy of a short course on cancer pain management. Eighty-six final-year medical students completed a 22-item questionnaire assessing their knowledge and attitudes toward the use of morphine for cancer pain. Students indicated their agreement with each statement on a four-point scale (one, strongly disagree; four, strongly agree). All students then completed a compulsory short course on pain management. The course content included a 1-hr lecture on chronic nonmalignant pain, a 1-hr lecture on acute pain management, and a 1-hr lecture on cancer pain management. In addition, students completed small-group, problem-based learning modules on several aspects of pain management. After the course, all students completed the same 22-item survey. The alpha reliability score of the pretest instrument was 0.55, and the posttest reliability was 0.86. Upon course completion, students agreed most strongly (mean +/- SEM) that morphine should be given on a regular schedule for cancer pain (3.41 +/- 0.08), that cancer pain management frequently requires co-analgesics (3.36 +/- 0.06), and that patients with good pain relief function better than those with continuing pain (3.39 +/- 0.08). A comparison of pretest and posttest means on specific items suggested that the greatest amount of learning took place in the following content areas: morphine is a good oral analgesic; increases in cancer pain should be treated by increasing the morphine dose; respiratory depression is not a concern for cancer pain patients; and morphine can be used over a wide range of doses. The regular use of morphine was recognized as the treatment drug of choice for cancer pain. The students showed improved knowledge scores on ten of the 22 items on the posttest survey. A significant increase in learning occurred on six knowledge and attitude items. On only one item (nausea as a side effect of morphine) did the knowledge scores decrease on the posttest. A significant minority (40%) of senior medical students had deficits in knowledge about the use of morphine for cancer pain. The risk of addiction, respiratory depression, and tolerance were misunderstood by a significant minority (25%) of students.
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PMID:Medical student knowledge of morphine for the management of cancer pain. 967 Jun 36


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