Morphine and alternative opioids in cancer pain: the EAPC recommendations

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.     

四种阿片类镇痛药用于癌性疼痛治疗的药物经济学评价

目的:探讨盐酸吗啡缓释片(美菲康)、硫酸吗啡缓释片(美施康定)、盐酸羟考酮控释片(奥施康定)、芬太尼透皮贴剂(多瑞吉)用于癌性疼痛患者镇痛治疗的成本效果,为临床合理用药提供指导。方法:随机调查2011年2月至2012年4月我院240例分别使用美菲康(58例)、美施康定(60例)、奥施康定(62例)和多瑞吉(60例)治疗晚期癌痛的住院患者。美菲康给药初始剂量为30mg,q12h,美施康定给药初始剂量为30mg,q12h,奥施康定给药初始剂量为10mg,q12h,多瑞吉外用贴于皮肤,起始剂量4.2mg,q72h,治疗中出现暴发痛者给予硫酸吗啡即释片,根据疼痛缓解情况决定剂量的调整直至将疼痛缓解至病人满意的程度即VAS 0-3分。不良反应给予对症处理。比较用药一个月后的镇痛疗效、不良反应及用药成本,运用药物经济学成本-效果分析法评价四组治疗方案。结果:美菲康、美施康定、奥施康定和多瑞吉的疼痛缓解率分别为91.38%、91.67%、93.55%、93.33%,四组无显著性差异(P>0.05)。人均成本分别为1279.26元、1346.53元、1507.66元、2018.12元,成本-效果比分别为13.40、14.68、16.12、21.62。结论:美菲康、美施康定、奥施康定和多瑞吉用于晚期癌痛患者镇痛疗效相当,从药物经济学角度来看,美菲康是癌痛患者镇痛治疗的较佳选择。     

Adjuvant analgesics in cancer pain management

Adjuvant analgesics are defined as drugs with a primary indication other than pain that have analgesic properties in some painful conditions. The group includes numerous drugs in diverse classes. Although the widespread use of these drugs as first-line agents in chronic nonmalignant pain syndromes suggests that the term "adjuvant" is a misnomer, they usually are combined with a less-than-satisfactory opioid regimen when administered for cancer pain. Some adjuvant analgesics are useful in several painful conditions and are described as multipurpose adjuvant analgesics (antidepressants, corticosteroids, alpha(2)-adrenergic agonists, neuroleptics), whereas others are specific for neuropathic pain (anticonvulsants, local anesthetics, N-methyl-D-aspartate receptor antagonists), bone pain (calcitonin, bisphosphonates, radiopharmaceuticals), musculoskeletal pain (muscle relaxants), or pain from bowel obstruction (octreotide, anticholinergics). This article reviews the evidence supporting the use of each class of adjuvant analgesic for the treatment of pain in cancer patients and provides a comprehensive outline of dosing recommendations, side effects, and drug interactions.     

Opioid analgesics in cancer pain: current practice and controversies

Pain is a complex somato psychic experience that requires a multimodality approach to treatment. Pharmacologically, pain in cancer can be divided into opioid non-responsive, opioid partially responsive, opioid responsive (but do not use opioids) and opioid responsive (do use opioids). Three concepts govern the use of analgesics in opioid responsive pains: 'by the mouth', 'by the clock' and 'by the ladder'. Adjuvant drugs may also be necessary. Morphine is the strong opioid of choice for cancer pain. In patients unable to take oral medication, morphine can be administered by suppository, by injection or peridurally. Useful alternative strong opioids include phenazocine, hydromorphone and buprenorphine. A number of controversial issues are discussed. These include the oral to parenteral potency ratio of morphine; the main site of metabolism of morphine; the relative merits of morphine and diamorphine; the risk of respiratory depression; the development of tolerance; and the risk of addiction.     

Understanding opioid tolerance in cancer pain

PURPOSE/OBJECTIVES: To review opioid tolerance in chronic cancer pain, define the phenomenon and its scope, review physiologic mechanisms, and discuss clinical strategies to identify and manage this complex issue. DATA SOURCES: Review articles, case studies, original research, and published guidelines. DATA SYNTHESIS: Novel therapies to prevent/reverse tolerance are being investigated with a possible future role for N-methyl-d-aspartate antagonists. CONCLUSIONS: Greater nursing research is needed to identify patient risk factors for tolerance development and clinical measurement of the phenomenon. Understanding cellular mechanisms for tolerance may contribute to better management. IMPLICATIONS FOR NURSING PRACTICE: Nursing knowledge of tolerance is important to provide the basis for accurate patient assessment, education, and pain management.     

Evolving knowledge of opioid genetics in cancer pain

Inter-individual variation in response to opioids for cancer pain is a well-established phenomenon. Variation occurs in the dose of opioid required, the analgesic efficacy of the opioid and also in the side-effects experienced by the individual taking the drug. To date, no clinical factor has been identified that can reliably explain or predict such variation. In recent years there has been growing interest in the possibility that genetic factors may play a role in the variability in opioid response. The aims of this review are to present the evidence supporting pharmacogenetic research in this area, to evaluate some of the studies and results that have been published to date and to present some of the challenges for future research in this area.     

辅助镇痛药物在癌痛治疗中的应用进展*

辅助镇痛药物是指作用机制各不相同、原本用于治疗某种疾病,之后发现兼具镇痛作用的一组药物。由于癌痛机制复杂,所以经常需要阿片药物、非甾体类药物和辅助药物联合镇痛。根据WHO三阶梯镇痛原则,辅助药物可以用于癌痛治疗的任何一个阶梯,与阿片类药物联合应用具有协同镇痛、减少阿片类药物用量、减轻阿片类药物不良反应的作用,尤其适用于对阿片类药物部分敏感的神经病理性疼痛。常用的辅助镇痛药物包括：抗抑郁药、抗惊厥药、局部用药、皮质类固醇激素以及NMDA受体拮抗剂等,这些药物在辅助镇痛时与原本治疗疾病的用法用量有所不同,临床医生应该熟知其不良反应,并从小剂量开始,经过数天或数周的逐步加量达到最佳效果与不良反应的平衡。     

Formulary availability and regulatory barriers to accessibility of opioids for cancer pain in Europe: a report from the ESMO/EAPC Opioid Policy Initiative

BackgroundMany patients in Europe do not receive adequate relief of pain because of excessive regulatory restrictions on the availability and accessibility of opioids. This is a major public health problem. The aim of the study is to evaluate and report on opioid availability and the legal and regulatory barriers to accessibility across the countries of Europe.MethodsEuropean Society for Medical Oncology and European Association for Palliative Care national representatives reported data regarding survey of opioid availability and accessibility. Formulary adequacy is evaluated relative to the World Health Organization (WHO) essential drugs list and the International Association for Hospice and Palliative Care list of essential medicines for palliative care. Overregulation is evaluated according to the guidelines for assessment of national opioid regulations of the WHO.ResultsData were reported on the availability and accessibility of opioids for the management of cancer pain in 21 Eastern European countries and 20 Western European countries. Results are presented describing the availability and cost of opioids for cancer pain in each surveyed country and nine forms of regulatory restrictions.ConclusionsUsing standards derived from the WHO and International Narcotics Control Board, this survey has exposed formulary deficiencies and excessive regulatory barriers that interfere with appropriate patient care in many European countries. There is an ethical and public health imperative to address these issues.     

Interdisciplinary evidence-based recommendations for the follow-up of testicular germ cell cancer patients

Over the last years, clear treatment recommendations for patients with testicular cancer have been published. This has led to significant improvements in outcome and survival. Moreover, active surveillance has become a cornerstone in the management of clinical stage I seminomatous and non-seminomatous germ cell tumors. On the other hand, the existing recommendations for the follow-up of testis cancer patients are unclear and differ widely. Follow-up recommendations in this young patient population have to be as evidence based as possible, feasible in order to ensure adherence, and must not be harmful. Therefore, attention has to be paid to the negative impact of unnecessary radiation exposure. Recently, new evidence became available regarding the relapse pattern of different disease stages of testicular cancer, the use of imaging at follow-up, and the risks of excessive radiation due to imaging, and in particular that of computed tomography (CT) scans. This article summarizes the recommendations for follow-up of testicular cancer patients of an interdisciplinary multinational working group consisting of urologists, medical oncologists, and radiation oncologists.     

The management of neuropathic pain in cancer: clinical guidelines for the use of adjuvant analgesics

Neuropathic pain is seen in a third of cancer patients and is not always responsive to traditional analgesics. We describe practical guidelines for the use antidepressants and anticonvulsants as adjuvant analgesics in such situations. Newer adjuvant analgesics, interventional procedures and options for the management of pain emergencies, are also briefly outlined.     

Use of analgesics and risk of renal cell cancer

Although heavy or long-term use of analgesics has been related to risk of renal cell cancer in several studies, evidence for such an association remains inconclusive. In a populationbased case-control study including 440 renal cell cancer cases, spouses of an additional 151 cases, and 691 controls, we assessed renal cell cancer risk associated with lifetime consumption among those who reported during in-person interviews regular (at least 2 or more times per week for I month or longer) use of analgesics. Odds ratios (OR) were computed using logistic regression analyses. No excess risk was associated with regular use of aspirin, acetaminophen, phenacetin or combinations of these agents, nor did risks rise with increasing cumulative intake of these analgesics. A non-significant increased risk (OR = 2.1, 95% CI = 0.6–6.9) was observed among women who used only acetaminophen-containing analgesics, but little excess was seen in men. Earlier studies reported a link to phenacetin-containing analgesics, but no one reported exclusive use of phenacetin-containing drugs in our study. The findings suggest that use of analgesics is not likely to play a major role in renal cell cancer development and that for cases diagnosed in the late 1980s or later, after the earlier withdrawal of phenacetin-containing drugs from the market, a hazard from this analgesic no longer exists. © 1994 Wiley-Liss, Inc.     

Interventional therapies for cancer pain management: important adjuvants to systemic analgesics

Optimized use of systemic analgesics fails to adequately control pain in some patients with cancer. Commonly used analgesics, including opioids, nonopioids (acetaminophen and non-steroidal anti-inflammatory drugs), and adjuvant analgesics (anticonvulsants and antidepressants), have limited analgesic efficacy, and their use is often associated with adverse effects. Without adequate pain control, patients with cancer not only experience the anguish of poorly controlled pain but also have greatly diminished quality of life and may even have reduced life expectancy. Interventional pain therapies are a diverse set of procedural techniques for controlling pain that may be useful when systemic analgesics fail to provide adequate control of cancer pain or when the adverse effects of systemic analgesics cannot be managed reasonably. Commonly used interventional therapies for cancer pain include neurolytic neural blockade, spinal administration of analgesics, and vertebroplasty. Compared with systemic analgesics, which generally have broad indications for control of pain, individual interventional therapies generally have specific, narrow indications. When appropriately selected and implemented, interventional pain therapies are important components of broad, multimodal cancer pain management that significantly increases the proportion of patients able to experience adequate pain control.     

阿片类药物治疗终末期癌痛患者的临床分析

目的：分析终末期癌症患者应用阿片类镇痛药物的剂量与安全性。方法：回顾性分析181例终末期癌症患者中138例（76．3％）用阿片类药物镇痛，比较不同性别、年龄、原发肿瘤部位和转移部位阿片镇痛药物疗效及副作用。结果：可评价的138例中，用硫酸吗啡控释片（美施康定）105例（76．1％），芬太尼透皮帖剂（多瑞吉）21例（15．3％），弱阿片类12例（8．7％）。日平均吗啡口服量男性高于女性（P=0．02）；随着年龄增大，用药剂量减少（P〈0．05），不同部位肿瘤患者用量无明显差异（P〉0．05）。用硫酸吗啡控释片发生呼吸抑制需解救者4例（3．8％），便秘发生率11．4％。无药物过量致死亡患者。结论：阿片类镇痛药物使用剂量与性别和年龄有一定关系，原发病灶与剂量无关，不良反应可控制。     

268例门诊癌痛患者镇痛药品用药分析

目的 分析评估某院近3年门诊癌痛患者麻醉镇痛药品的应用情况,探讨镇痛治疗策略,为临床合理应用该类药物提供依据.方法 选择门诊收治的268例癌痛患者为对象,记录其所用药品名称、用药量、使用天数、病种等,并进行逐份统计、整理、分析,比较治疗前后患者疼痛程度、生活质量等的差异.结果268例癌痛患者常用的阿片类镇痛药有5种,排序由高到低分别为盐酸羟考酮缓释片、芬太尼透皮贴剂、硫酸吗啡缓释片、盐酸吗啡片和磷酸可待因片.268例癌痛患者中,肺癌患者最多(26.5%);盐酸羟考酮缓释片的使用量最多;有36例患者用药时间超过1年.与治疗前相比,患者的痛感程度得到了缓解,疼痛数字评分(NRS)降低,卡氏功能状态评分(KPS)增加,治疗前后比较,差异均有统计学意义(P﹤0.05).结论 门诊癌痛治疗基本符合WHO癌痛治疗原则,但仍存在一定的问题,有待于进一步规范完善.     

The role of bisphosphonates in the treatment of prostate cancer: recommendations from an expert panel

In this study, we provide consensus guidelines for the use of bisphosphonates in men with prostate cancer. To this end, an expert panel composed of urologists, medical oncologists, radiation oncologists, and endocrinologists met to review current clinical evidence for the use of bisphosphonates in patients with different stages of prostate cancer to derive consensus recommendations. Physicians should be proactive in monitoring bone loss in patients receiving long-term androgen-deprivation therapy for prostate cancer. Further study is needed before recommending the routine use of bisphosphonates in men with nonmetastatic prostate cancer. However, if a patient has clinically significant bone loss, use of a bisphosphonate to prevent further compromise of bone integrity should be strongly considered, regardless of hormonal and metastatic status. Bone scans are the preferred method for the identification of bone metastases. In patients with hormonerefractory prostate cancer and bone metastases, zoledronic acid is the only bisphosphonate indicated for the prevention of skeletal complications. In conclusion, patients with prostate cancer are at high risk for skeletal morbidity. Bisphosphonates have been shown to prevent cancer treatment-induced bone loss in men receiving androgen-deprivation therapy as well as skeletal complications in men with bone metastases. However, further study of the use of bisphosphonates across the clinical spectrum of prostate cancer is needed.