Rapid switching between transdermal fentanyl and methadone in cancer patients.

PURPOSE: The aim of this study was to examine the clinical effects of switching from transdermal (TTS) fentanyl to methadone, or vice versa, in patients with a poor response to the previous opioid. PATIENTS AND METHODS: A prospective study was carried out on 31 patients who switched from TTS fentanyl to oral methadone, or vice versa, because of poor opioid response. A fixed conversion ratio of fentanyl to methadone of 1:20 was started and assisted by rescue doses of opioids, and then doses were changed according to clinical response. Pain and symptom intensity, expressed as distress score, were recorded before switching doses of the two opioids and after subsequent doses. The number of changes of the daily doses, time to achieve stabilization, and hospital stay were also recorded. RESULTS: Eighteen patients were switched from TTS fentanyl to methadone, and seven patients were switched from methadone to TTS fentanyl. A significant decrease in pain and symptom intensity, expressed as symptom distress score, was found within 24 hours after switching took place in both directions. Unsuccessful switching occurred in six patients, who were subsequently treated with an alternative therapy. CONCLUSION: A rapid switching using an initial fixed ratio of fentanyl to methadone of 1:20 is an effective method to improve the balance between analgesia and adverse effects in cancer patients with poor response to the previous opioid. No relationship between the final opioid dose and the dose of the previous opioid has been found.     

Opioid switch to oral methadone in cancer pain

The occurrence of undesirable side effects due to opioids (delirium, confusion, myoclonus, nausea, emesis) is one of the major complications in the management of pain, especially in chronic cancer pain states. Methadone, as an alternative to morphine, has been proposed in the control of opioid-induced toxicity. Methadone is a synthetic opioid, with mu and delta receptor activity, associated with the capacity to inhibit N-methyl-D-aspartate receptors. Questions have arisen concerning its equianalgesic ratio since its rediscovery over the past few years and are certainly related to its receptor interactions. Aspects of its pharmacology, indications, and switching modalities are discussed here. Opioid rotation is a new tool in the management of cancer pain, deserving more attention.     

晚期肺癌癌痛患者口服吗啡转换为芬太尼贴剂的临床疗效

目的探讨晚期肺癌癌痛患者由口服吗啡转换应用芬太尼透皮贴剂的临床疗效。方法59例口服吗啡镇痛不满意的晚期肺癌伴重度癌痛患者,换用芬太尼透皮贴剂止痛,剂量换算公式为：芬太尼透皮贴剂72h剂量（μg/h）=口服吗啡（mg/d）×0．5,根据疼痛评分调整剂量,将疼痛控制在3分以下。数字评分法记录疼痛强度、生活质量和不良反应评分。结果59例晚期肺癌癌痛患者药物转换后疼痛强度明显降低,转换前疼痛评分均值为（6．27±1．15）分,转换后6d为（2．15±0．87）分,15d为（2．03±0．68）分,30d为（1．95±0．73）分（P〈0．01）。总的疼痛缓解率81．35％。转换后生活质量评分明显提高（P〈0．05）,不良反应如恶心／呕吐和便秘发生率降低,但皮肤瘙痒的发生率提高（P〈0．05）。结论无法应用口服吗啡镇痛的晚期肺癌癌痛患者,转换应用芬太尼贴剂后,镇痛效果提高,生活质量得到明显改善。     

Treatment of cancer pain with transdermal fentanyl

Pain is a feature of many cancers, particularly in the advanced stages at which the palliative care approach to symptom control achieves the best outcomes. The holistic approach generally dictates that any treatment of the cancer per se has symptom control as the primary objective at this advanced stage. Pain, which invariably increases with disease progression, is treated with opioids and adjuvant analgesic drugs together with physical therapies. Orally administered opioid drugs are used preferentially because of cost and convenience, but other routes of administration (subcutaneous, rectal, spinal) are also possible. More recently, transdermal fentanyl has been evaluated in the treatment of moderate to severe cancer pain. The rate of fentanyl absorption is constant (after a lag period), and the dose is altered by increasing or decreasing the area of skin covered by the patch (size and/or number of patches). The dosing interval for these systems is generally 3 days. The extent of pain relief provided by transdermal fentanyl and sustained release morphine formulations is similar, with quality-of-life instruments showing no consistent preference for either formulation. Open studies have suggested a lower risk of constipation. Transdermal fentanyl is effective in the treatment of severe cancer pain, particularly when the oral route is unavailable.     

口服控释吗啡交替为芬太尼透皮贴剂的疗效分析

目的评价晚期癌痛患者由口服控释吗啡转换为芬太尼透皮贴剂止痛的疗效与不良反应。方法 40例口服控释吗啡镇痛不满意的晚期癌痛患者,交替为芬太尼透皮贴剂,吗啡与芬太尼贴剂的剂量换算比为100∶1。采用0～10视觉模拟评分法评价疼痛强度,评分降低≥2表示疼痛缓解有临床显著性差异;不良反应评估分为4级:无不良反应(0)、轻度(1)、中度(2)或重度(3)。结果药物交替后疼痛强度明显降低,转换前平均疼痛评分为5.7,转换后7 d降至3.4。发生至少一种不良反应的患者转换前为37例(92.5%),转换后降至25例(62.5%)。结论将口服控释吗啡交替为芬太尼透皮贴剂是一种安全有效的镇痛策略。     

多瑞吉对恶性肿瘤治疗相关性疼痛止痛作用的前瞻性研究

目的 探讨用芬太尼贴剂(多瑞吉)治疗恶性肿瘤放化疗所致中重度口腔黏膜疼痛的可行性及安全性.方法 采用前瞻性随机对照研究的方法,将恶性肿瘤放、放化后出现口腔疼痛视觉评分(VAS)≥4分的患者,随机分为研究组和对照组:对照组仅给予VitBco漱口水含漱;研究组在此基础上加用多瑞吉治疗,起始剂量为2.5 mg,每3天更换,据疼痛程度调整.结果 研究组疼痛缓解率为87.8﹪,而对照组为43.48﹪,差异有统计学意义(P＜0.05);多瑞吉平均起效时间2.78±0.96天.研究组和对照组在进食时疼痛评分、进食恐惧感、对普鲁卡因的依赖、对治疗的信心及睡眠等方面的差异有统计学意义(P＜0.05).不良反应主要表现为头昏、呕吐等,经对症治疗后可明显改善,未出现对多瑞吉成瘾及其他严重的不良反应.结论 多瑞吉对恶性肿瘤放化疗所致口腔疼痛有较好的止痛效果,且较迅速、安全,对放化疗所致中重度口腔疼痛而服用止痛药物困难的患者又提供了一个好的止痛方法.     

Inter- and intra-individual variability in transdermal fentanyl absorption in cancer pain patients

A transdermal therapeutic system (TTS) is recommended for use in chronic cancer pain, particularly in the advanced stages. The aim of this trial was to study intra- and interindividual variabilities in fentanyl transdermal absorption and investigate physiological and clinical parameters that can influence the absorption in patients treated using a TTS for moderate to severe cancer pain. The study group consisted of 108 patients (71 men and 37 women; mean age, 61.3 years) with chronic cancer pain. A total of 507 patches were analysed. The TTSs used to administer fentanyl were removed after a 72-h period. The amount of fentanyl remaining in the patches was determined using a high-performance liquid chromatography method with ultraviolet detection. Depending on the analgesic requirements of the patient, the dose of fentanyl administered by TTS ranged from 25 to 500 microg/h. The study period was 6 months. Large interindividual variability in the amount of remaining fentanyl in the patches occurred. For 58.1% of patches, absorption was 60 to 84%; for 33.2% of them, it was lower; and for 8.8%, it was higher than this range. The intra-individual variability ranged from 2.8 to 75.1%. The bioavailability of fentanyl was statistically different according to patient age. Patients >75 years of age absorbed 50% of the fentanyl during the selected 72-h period, whereas patients <65 years absorbed 66%. Moreover, there is a significant difference in the percentage of absorbed fentanyl according to the type of cancer. The absorption was higher in patients with breast or digestive cancer than in those with lung cancer. Hyperhidrosis, hypertrichosis and the localization of patches on the skin did not influence bioavailability. For the entire group, transdermal fentanyl treatment provided good to excellent pain relief in the majority of patients.     

芬太尼透皮贴剂治疗30例中度、重度癌痛

目的：研究芬太尼透皮贴剂用于癌痛患者的镇痛效果、不良反应及使用后患者生活质量的改善。方法：30例中度或重度癌痛的患者，使用芬太尼透皮贴剂。记录有后的疼痛强度、生活质量评分及用药后的不良反应，加以归纳总结。结果：芬太尼透皮贴剂使用后，全部患者均获中度以上缓解。其中安全缓解13例（43.33%)，明显缓解16例（53.33%），中度缓解1例（3.33%）。不良反应有恶心、呕吐、便秘、头晕及嗜睡等，但发生率较低，患者的生活质量均得到明显改善。结论：对于中度或重度癌痛的患者，使用芬太尼透皮贴剂，能安全、有效和简单的控制癌痛，改善生活质量且不良反应发生率较低。     

芬太尼透皮贴剂与口服吗啡用于癌痛病人的比较

目的　比较芬太尼透皮贴剂与口服吗啡用于癌痛病人的副作用。方法　癌痛病人 5 6例 ,随机分为两组 ,每组 2 8例。组A应用芬太尼 5mg/贴 /3d ,按剂量换算 ,组B应用口服缓释吗啡 5 0mg ,2次 /d。应用 9d后 ,采用视觉模拟评分法 (VAS法 )评价止痛疗效 ,同时比较两组副作用。结果　两组用药后止痛效果明显 ,两组间疼痛缓解程度无显著差异 (P >0 .0 5 ) ,两组副作用中便秘的发生率却有显著性差异 (P <0 .0 1)。结论　应用芬太尼透皮贴剂用于癌痛病人的便秘发生率较口服吗啡低。     

Long-term cancer pain management in morphine pre-treated and opioid naive patients with transdermal fentanyl

There is emerging data supporting the use of TTS-F (transdermal therapeutic system-fentanyl) in opioid naive patients. Our study examines the safety and efficacy of TTS-F in the long-term control of cancer pain in opioid naive patients and those transferring from oral morphine. Pain was assessed in 589 patients (Group A: 268 opioid naive, Group B: 321 transferring from morphine) using a Visual Analogue Scale (VAS; 0-10), based on selected questions from the Greek Brief Pain Inventory (GBPI). Overall treatment satisfaction was assessed on a 4-point scale. Quality of Life (QOL) and ECOG (0-4) status were also recorded. These were assessed in relation to TTS-F dose, pain type (neuropathic, combined, nociceptive), concomitant use of anti-inflammatory drugs and other demographic data. Of 589 patients, 59 (10%) withdrew as a result of inadequate pain satisfaction or for other reasons. There were no discontinuations due to side effects; no Grade 3-4 events occurred. A total of 530 continued on-study, 211 patients died during study period and 295 departed; all (506; 89%) were satisfied with their pain relief. Analysis of patients at baseline, 28 days, 6 and 12 month time points (n = 153 Group A; n = 214 Group B) with respect to QOL and pain measures indicated a statistically significant (p < 0.001) improvement in all measures across time independent of pain type, or any other patient characteristic(s). In patients with intolerable pain, transfer to TTS-F offers an efficient and safe long-term analgesic option. TTS-F offers durable long-term maintenance of pain relief with acceptable side effects in opioid naive patients. In general, TTS-F as a first line analgesic approach for carefully selected and monitored patients experiencing moderate to severe cancer pain should be considered.     

Three-day-type transdermal fentanyl patch conversion by rapid titration method with short-acting oral oxycodone for cancer pain

This study compared the efficacy and safety of a 3-day-type transdermal fentanyl patch conversion by the rapid titration method to short-acting oral oxycodone for cancer pain.We evaluated seven hospitalized cancer patients who had moderate to severe cancer pain.Pain intensity was rated using an 11-point(0-10)numerical rating scale(NRS).All 7 patients initially reported their pain intensity at rest as NRS≥4 during treatment by Non-Steroidal Anti-Inflammatory Drugs(NSAIDs).Short - acting oral oxycodone(OxiNorm?)5 mg was administered to all patients.One hour after short-acting oral oxycodone was administered, pain assessment was carried out using NRS by the author.Short -acting oral oxycodone was administered four times a day periodically, and as a rescue dose.If the total daily dose of short-acting oral oxycodone was stable for 2 days, we switched to the 3-day-type transdermal fentanyl patch.The optimal dosage of the 3-day-type transdermal fentanyl patch was determined by titration of short-acting oral oxycodone.All 7 patients reported mild levels(NRS≤2)of cancer pain for 2 days.No serious side effects were reported.The 3-day-type transdermal fentanyl patch conversion by the rapid titration method with short-acting oral oxycodone can be accomplished safely and effectively for patients with moderate cancer pain.     

Rapid switching from morphine to methadone in cancer patients with poor response to morphine.

PURPOSE: The aim of this study was to evidence the clinical effects of an abrupt substitution of morphine with methadone using a fixed ratio of 1:5 in patients for whom limiting adverse effects occurred before adequate analgesia was achieved with oral morphine. PATIENTS AND METHODS: A cross-sectional prospective study was carried out on 24 consecutive patients who were switched from oral morphine to oral methadone because they experienced substantial adverse effects that limited further increase in morphine dose. A fixed conversion morphine-to-methadone ratio of 5:1 was chosen. Subsequently, doses were changed according to clinical need, with frequent visits or phone contacts. Pain and symptom intensity, preswitching doses of morphine, initial and subsequent doses of methadone, and survival were recorded. RESULTS: A significant decrease in pain and symptom intensity was found within 24 hours after the substitution took place. The switching was effective in most patients (19 of 24), although five patients required alternative treatments. No significant changes in methadone dose were reported in the 3 days after switching. Methadone dose was significantly higher in patients who had lower preswitching doses of morphine and vice versa. No relevant complications were reported. CONCLUSION: A rapid substitution of morphine with methadone using an initial fixed ratio of 5:1 is a safe and effective method for improving the balance between analgesia and adverse effects in cancer patients with poor morphine response. An appropriate system of patient monitoring is necessary, because further changes in dose may be required according to clinical needs.     

芬太尼透皮贴剂(芬太克)治疗癌性疼痛临床疗效观察

目的:观察芬太尼透皮贴剂(芬太克)治疗癌性疼痛的疗效、不良反应及对生活质量的影响。方法:采用芬太尼透皮贴剂(芬太克)对50例癌性疼痛患者镇痛治疗,每24小时评定疼痛强度、生活质量及不良反应。结果:疼痛完全缓解36例,部分缓解10例;患者生活质量明显改善,不良反应发生率低,主要为便秘,恶心、呕吐及头昏等。结论:芬太尼透皮贴剂(芬太克)治疗癌性疼痛效果良好,不良反应低,能提高生活质量。     

芬太尼透皮贴剂治疗肺癌骨转移疼痛50例临床观察

目的：观察芬太尼透皮帖剂治疗肺癌骨转移的镇痛效果，不良反应及生活质量的改善程度。方法：选取50例中重度疼痛的肺癌骨转移患者，使用芬太尼透皮贴剂，记录治疗前后疼痛强度，生活质量评分和用药的不良反应。结果：使用芬太尼透皮贴剂后，全部患者均获得中度以上缓解，其中完全缓解20例（40．0）％，明显缓解22例（44．0％），中度缓解8例（16．0％），不良反应发生率较低，主要有恶心、呕吐、嗜睡等，患者的生活质量得到明显改善。结论：芬太尼透皮贴剂治疗中重度疼痛疗效显著。     

吗啡滴定给药与芬太尼透皮贴联合治疗晚期重度癌痛的临床疗效观察

目的：观察吗啡滴定给药与芬太尼透皮贴联合治疗因晚期消化道恶性肿瘤所引起重度癌痛患者的临床疗效。方法：40例晚期消化道的恶性肿瘤患者,用吗啡滴定给药与芬太尼透皮贴联合止痛治疗,观察疗效及不良反应。结果：40例晚期消化道的恶性肿瘤患者的疼痛均得到良好控制,72h 后评估发现大部分患者睡眠改善、食欲增加、精神好转。而且因单用吗啡所致的如便秘、恶心、呕吐、头晕等药物不良反应发生率也低。结论：吗啡滴定给药与芬太尼透皮贴联合治疗能有效控制重度癌痛并且不良反应发生率低。     

Patient-controlled analgesia with oral methadone in cancer pain: Preliminary report

BACKGROUND:: Methadone is a very useful drug in cancer pain because of itslow cost, lack of active metabolites, high oral availability,and the rapid onset of its analgesic effect. It seems to bewell tolerated in patients with difficult pain syndromes whoare receiving high doses of opioids, and it may deter the developmentof tolerance, but a high individual variation in terminal eliminationhalf-life can result in different rates and extents of drugaccumulation. For this reason, oral patient-controlled analgesiawith methadone was used in 24 advanced-disease patients withpain. PATIENTS AND METHODS:: A regimen of self-administered oral methadone at fixed dosesand flexible patient-controlled dosage intervals to achieveadequate analgesia, while avoiding toxic effects of methadoneaccumulation, was used in 24 patients requiring opioid therapy.After a priming period of three days with fixed doses of 3–5mg three times a day for naïve patients and 50% of themorphine equivalent of methadone in patients switched from morphine,patients and relatives were instructed to maintain the night-timedose and to administer a second dose when the pain recurred.When than four doses of methadone a day were used, an increaseof the dosage was prescribed. Continuous pain assessment andmonitoring of symptoms were offered. RESULTS:: The majority of patients achieved good pain relief until death,and three were switched to very low doses of subcutaneous morphinein their final days. The methadone escalation index was about2% a day, with a mean dosage increase of 0.3 mg a day for anaverage of 60 days of treatment at doses ranging from 9 to 80rug. The plasma concentration in 14 patients ranged from 0.013to 0.273 mcg/ml with dosages of 20–80 mg during chronictreatment. A mean of 2.4 doses a day was reported, includingthe fixed night-time dose. The extent of side effects was consideredacceptable. CONCLUSION:: Patient-administered analgesia with oral methadone appears tobe a simple, cheap and relatively safe technique for controllingcancer pain, permitting individualization by the patient him-or herself and avoiding the risk of accumulation. Continuousassessment is necessary. cancer pain, methadone, patient-controlled analgesia     

芬太尼透皮贴剂治疗中重度癌痛的疗效观察

晚期癌痛患者43例,均为中、重度疼痛,在使用芬太尼透皮贴剂前后观察疼痛强度、生活质量评分及用药后的不良反应.结果总有效率为88.3%(38/43),其中完全缓解13例(30.2%),明显缓解25例(58.1%);不良反应有头晕、恶心、呕吐、胃部不适、便秘等,但发生率低.初步研究结果提示.芬太尼透皮贴剂治疗中、重度癌痛,可使患者生活质量明显改善.     

小剂量芬太尼治疗中度癌痛疗效与满意度

为了观察小剂量芬太尼透皮贴剂治疗中度慢性癌痛的疗效、不良反应及满意度.将43例中度癌痛患者,根据既往使用的镇痛药决定芬太尼初始剂量并分为2组.A组(2.5 mg)28例已口服弱阿片药物;B组(1.25 mg)15例使用非阿片类药镇痛但效果差.观察疼痛缓解程度、生活质量改善、不良反应及满意度.结果使用芬太尼贴剂后疼痛缓解率100%(Ⅲ度58.1%+Ⅳ度41.9%),最终滴定剂量≤25 μg/h,A组60.7%,B组86.6%,两组之间治疗前后疼痛评分差异无统计学意义,P＞0.05.生活质量得到改善,尤以睡眠和食欲改善最为显著.不良反应为轻度头晕、嗜睡、恶心呕吐、便秘等.自身对比显示,使用芬太尼贴剂较使用弱阿片药物满意度高,两组差异有统计学意义,P＜0.05.初步临床观察结果显示,小剂量芬太尼透皮贴剂可作为治疗中度慢性癌痛的首选方法之一.肿瘤防治杂志,2004,11(10)1099-1100     

癌痛患者芬太尼静脉自控镇痛滴定芬太尼透皮贴剂的临床观察

目的 探讨癌痛患者芬太尼静脉自控镇痛（PCIA）滴定芬太尼透皮贴剂（多瑞吉）的安全性和有效性。方法 收集2011年12月至2013年8月我院收治的中重度癌痛患者26例,采用芬太尼PCIA滴定多瑞吉治疗癌性疼痛,分为4个治疗时段（PCIA前、PCIA时、PCIA+多瑞吉和多瑞吉）记录滴定情况、疼痛评分、疼痛对生活的影响评分和不良反应。结果 26例患者中21例滴定成功,5例滴定失败。患者在芬太尼PCIA时、PCIA+多瑞吉和多瑞吉治疗后与PCIA治疗前比较,一般疼痛评分、最严重疼痛评分、活动时疼痛评分、静息时疼痛评分和疼痛对生活的影响评分均有显著下降（P＜0.05）。滴定主要不良反应为PCIA治疗中出现的恶心、呕吐,未观察到肌强直、意识丧失、呛咳、瘙痒、呼吸抑制和心动过缓发生。结论 癌痛患者PCIA滴定多瑞吉安全、有效、简单易行,并能迅速缓解爆发痛,值得临床推广。     

Direct conversion from low-dose morphine to transdermal fentanyl: efficacy for cancer pain and quality of life

The efficacy and QOL in a cancer pain patient who converted to transdermal fentanyl from low-dose morphine (n=5) or high-dose morphine (n=5) were retrospectively compared. Cancer pain control was evaluated by visual analogue scales (VAS) score. Patients switched from low-dose morphine demonstrated significantly better scales. The number of morphine rescues was also significantly less in the low-dose conversion group. In conclusion, conversion from low-dose morphine is useful for cancer pain control from the aspect of efficacy and QOL.