Retrospective study on intravenous compound injection of cancer pain patients with oxycodone and hydrocotarnine preparation in comparison with subcutaneous administration

In Japan, although oral oxycodone is widely used for cancer pain treatment, there is no injection preparation of oxycodone used as a single ingredient. Only the compound injection of oxycodone and hydrocotarnine has received approval. Subcutaneous administration of the drug is approved, but there are few efficacy and safety reports about its intravenous administration. We compared 245 patients(187 intravenous administration patients and, 58 subcutaneous administration patients)to whom the compound injection of oxycodone and hydrocotarnine was administered from April, 2008 to September, 2011, in order to investigate the drug's efficacy and safety. The reasons for injection were the impossibility of oral administration in 105 patients, a need for dose adjustment in 56 patients, and that other drugs were not as effective in 37 patients, and side effect reduction in 33 patients. The average change in the numeric rating scale(0-10)was 3. 7→1. 8 in intravenous administration, and 3. 4→1. 2 in subcutaneous administration. The incidence of main adverse events(intravenous administration/subcutaneous administration)were constipation(37%/28%), vomiting(31%/34%), and somnolence(52%/50%). There was no significant difference in efficacy and safety. The conversion ratio differed in a case due to a change, and about 20 to 40% of addition was needed within four days after the start. It is considered that compound injection of oxycodone and hydrocotarnine is effective for cancer pain treatment.     

盐酸羟考酮控释片阴道给药治疗癌性疼痛的临床研究

背景与目的：盐酸羟考酮控释片是治疗中重度癌性疼痛的强阿片类口服镇痛药,部分患者由于持续的恶心、呕吐、意识障碍或吞咽困难等,常使其口服应用受到限制。本研究目的是观察盐酸羟考酮控释片阴道给药方式治疗中重度癌性疼痛的疗效及不良反应,为口服药物困难的女性患者提供新选择。方法：36例不能口服药物中重度癌痛女性患者采用盐酸羟考酮控释片阴道给药方式治疗,以往未使用阿片类止痛药物者,初始盐酸羟考酮控释片剂量为10mg,每12h用药一次,剂量滴定参考口服给药方法：对凶不能继续口服盐酸羟考酮控释片而改用阴道给药方式者,继续原来剂量阴道给药。结果：36例患者中完全缓解6例,明显缓解20例,中度缓解和轻度缓解各4例,未缓解2例;中度以上疼痛缓解率为83．3％。中位起效时间为49min;中位镇痛时间为13．8h。主要不良反应为阴道烧灼感（9例,25．0％）,无因不良反应而中止治疗者。结论：盐酸羟考酮控释片阴道给药方式安全、有效、方便,在口服药物困难的女性患者是一种可选择的给药方式。     

羟考酮联合纳洛酮治疗癌痛的研究进展

许多患有癌症的人都有中度至重度的疼痛需要使用强效的镇痛药来缓解疼痛。阿片类药物为治疗晚期癌痛的主要药物（如吗啡、羟考酮等）。羟考酮是一种强效的阿片类镇痛药，可快速透过血脑屏障，口服给药后生物利用度高。但阿片类药物常常伴有很多的不良反应:恶心、呕吐、便秘、成瘾等，而羟考酮与纳洛酮联合用药不仅可以缓解病人的疼痛，而且可以减少不良反应的发生。本文对羟考酮联合纳洛酮对疼痛的治疗进展作一综述。     

Efficacy of controlled-release oxycodone for dyspnea in cancer patients--three case series

Dyspnea is a common symptom in patients with advanced cancer. Systemic morphine administration has been reported as an effective pharmacological treatment to control dyspnea. However, there have been few reports on similar effects of alternative opioids except for morphine. To evaluate the effect of controlled-release oxycodone on the relief of dyspnea, we investigated three cases with opioid substitution from subcutaneous morphine to oral oxycodone. In all cases, both opioids provided equivalent effects for the palliation of cancer dyspnea with no significant adverse effects. Future studies in the appropriate clinical designs will be needed to confirm our findings.     

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.     

Comparison of sustained-release morphine with sustained-release oxycodone in advanced cancer patients

The antinociceptive effect of morphine and oxycodone is mediated preferentially at micro and kappa receptors, respectively. The aim of this study was to evaluate the analgesic profile of the combination of morphine and oxycodone in cancer pain, compared to the standard administration of morphine alone. Controlled-release formulations of oxycodone (CRO) and morphine (CRM) were compared in 26 patients. The study started with an open-label, randomised titration phase to achieve stable pain control for 7 days, followed by a double-blind, randomised crossover phase in two periods, 14 days each. At any point, patients were allowed to use oral immediate-release morphine (IRM) as needed, in order to keep visual analogue scale < or =4. Pain, satisfaction, adverse effects and number of daily rescue morphine tablets were assessed. A total of 22 patients were evaluated. The weekly upload consumption ratio in morphine/oxycodone was 1 : 1.8 (1.80, 1.83, 1.76, 1.84). The weekly IRM consumption was higher in patients having CRM compared to patients having CRO (ratio morphine/oxycodone: 1.6, 1.6, 1.6, 1.7) (P<0.05). Patients receiving oxycodone complained of less nausea and vomiting. The rescue morphine analgesic consumption was 38% higher in patients receiving only morphine, compared to patients receiving both morphine and oxycodone. The results suggest that the combination of morphine/oxycodone (opioids with differential preferential sites of action) can be a useful alternative to morphine alone, resulting in a better analgesia profile and less emesis.     

盐酸羟考酮缓释片在食管癌患者癌痛治疗方面的疗效及安全性研究

目的 采用盐酸羟考酮缓释片对食管癌癌痛患者进行癌痛滴定,研究滴定后药物的作用以及药物的安全性.方法 选取食管癌癌痛患者100例,口服盐酸羟考酮,观察分析患者服药后的不良反应,记录滴定周期.结果 100例患者中,86.0％的患者在1个周期内完成滴定,2个周期内滴定完成率为12.0％,重度疼痛患者1个周期滴定完成率为20.0％(2/10),2个周期滴定完成率为70.0％(7/10),中度疼痛患者在前2个周期内滴定完成率高达98.9％;在治疗的早期阶段,患者出现不良反应的次数不断增加,甚至出现尿潴留,但是随着治疗的进行,患者逐渐不再出现不良反应.结论 盐酸羟考酮在治疗食管癌癌性疼痛中有很明显的优势,操作简单,且患者的不良反应少,安全可靠.     

两种剂量的盐酸羟考酮注射液治疗乳腺癌改良根治术后急性疼痛患者的效果比较

目的:探讨两种剂量的盐酸羟考酮注射液治疗乳腺癌改良根治术后急性疼痛患者的临床效果。方法:选取我院收治的120例择期全麻下行乳腺癌根治术治疗的患者进行研究,按照随机数字表法进行分组,60例患者为对照组,采用低剂量盐酸羟考酮注射液治疗,另60例为观察组,采用高剂量盐酸羟考酮注射液治疗,对比两组患者的镇痛效果、用药不良反应等。结果:两组患者在手术时间、麻醉时间、苏醒时间及拔管时间等指标方面对比均无较大差异性（P＞0.05）;拔除喉罩后5 min、0.5 h、2 h、4 h两组患者在疼痛程度评分方面（VAS）比较均无较大差异性（P＞0.05）,但拔除喉罩后8 h、12 h对比,观察组患者VAS评分明显低于对照组（P＜0.05）;两组患者在术后不良事件发生率及镇痛药物追加率方面对比均无较大差异性（P＞0.05）,麻醉前,两组患者心率、血压对比均无较大差异（P＞0.05）,给药后、苏醒期及恢复期两组各指标均有所变化,但两组间对比均无较大差异性（P＞0.05）。结论:采用高剂量的盐酸羟考酮注射液对乳腺癌改良根治术后急性疼痛患者进行治疗效果显著,能够在改善患者术后急性疼痛程度的同时避免增加术后不良事件,可在临床上推广应用。     

羟考酮缓释片联合即释吗啡在癌痛滴定治疗中的镇痛效果及不良反应

目的:观察盐酸羟考酮缓释片（奥施康定）联合即释吗啡在中、重度癌痛滴定治疗中的镇痛效果及不良反应。方法:选择82例中重度癌痛患者,随机分为A组（即释吗啡）和B组（羟考酮缓释片联合即释吗啡）,通过使用阿片类药物镇痛,对镇痛疗效、起效时间、滴定达到稳态时间、生活质量及不良反应进行观察及评估。结果:两组镇痛效果均显著,比较无明显差异性（P＞0.05）。B组较A组镇痛起效时间明显缩短,比较有明显差异性(P＜0.05),B组较A组滴定达到稳态时间明显缩短,比较有明显差异性(P＜0.05);两组生活质量均明显提高,比较无差异性(P＞0.05);两组便秘及恶心呕吐等不良反应的发生率均低,比较无差异性(P＞0.05）。结论:羟考酮缓释片联合即释吗啡治疗中、重度癌痛起效快、镇痛效果好,不良反应轻。     

107例大剂量盐酸羟考酮缓释片治疗中重度癌痛的有效性和安全性研究

目的探讨大剂量盐酸羟考酮缓释片(日剂量超过160 mg)治疗中重度癌痛患者的有效性和安全性。方法对2018年4月至2018年10月符合入组标准的107例患者进行回顾性研究,分析患者在达到大剂量前1天、大剂量治疗当日等5个时间点的疼痛评分、患者药物剂量和不良反应的发生情况。结果大剂量盐酸羟考酮完全缓解率(无痛患者比例)随治疗时间逐渐提高,治疗1周可达到6.54%。有效缓解率(疼痛评分≤3分患者比例)在治疗当日达到近50%,治疗1周可达到90%。患者治疗1周的盐酸羟考酮平均日剂量为228.88 mg。与大剂量盐酸羟考酮治疗前相比,大剂量盐酸羟考酮治疗后不良事件发生率的差异无统计学意义(P>0.05),治疗当日不良事件发生率最高为10.28%,随治疗时间延长而逐渐减低。结论大剂量盐酸羟考酮可有效缓解中重度疼痛,患者耐受性良好,值得在中重度癌痛临床治疗上进行推广。     

羟考酮替换盐酸吗啡减轻阿片类药物耐药的临床研究

目的研究羟考酮替换盐酸吗啡减轻癌症病人对阿片类药物耐药的影响。方法采用前瞻性自身对照试验,以1.5∶1作为各组病人吗啡向羟考酮转换的基础比率,用数字分级评分（NRS）、卡氏行为状态量表评分（KPS）和生活质量评分（QOL）作为转换前后镇痛效果、活动能力及生活质量的评价指标。结果不同剂量组盐酸吗啡与羟考酮的平均转换比率随着吗啡剂量的增加而增加,转换比值与吗啡的的剂量呈一次线性拟合趋势（F=0.003、P=0.954）,大剂量吗啡组比小剂量吗啡组替换后羟考酮的需要量更小。结论应用羟考酮替换大剂量盐酸吗啡止痛是一种减轻阿片类药物耐药的新途径。     

奥施康定联合唑来膦酸治疗骨转移性癌痛的临床研究

目的:观察奥施康定（盐酸羟考酮缓释片）联合唑来膦酸治疗骨转移性癌痛的临床疗效及安全性。方法:共纳入我院收治的286例骨转移性癌痛患者。根据患者疼痛评分给予奥司康定起始剂量，有爆发痛予即释吗啡止痛治疗，第二日根据前日总剂量调整奥施康定用量。1周后行注射用唑来膦酸4 mg输注，每4周重复用药。评价用药后患者止痛疗效、生活质量及毒副反应情况。结果:所有患者疼痛均有所缓解；奥施康定联合唑来膦酸治疗后，191例患者奥施康定用量减少，87例患者维持原剂量，仅有8例患者奥施康定用量增加。治疗前所有患者KPS评分为67.5±12.7,奥施康定治疗后KPS评分为73.8±18.3,奥施康定联合唑来膦酸治疗后KPS评分为78.4±17.1。治疗毒副反应主要为发热、一过性骨痛加剧、消化道症状及嗜睡等，经对症治疗后耐受性好。结论:奥施康定联合唑来膦酸治疗骨转移性癌痛具有较好的临床疗效和安全性，值得临床推广使用。     

盐酸羟考酮缓释片用于癌痛治疗的滴定*

盐酸羟考酮缓释片作为一种新型的强阿片类镇痛药,镇痛效果确切、口服安全性高、不良反应轻微,持续应用可提高癌痛患者的生存质量,是临床治疗中重度癌痛的首选药物之一。针对盐酸羟考酮缓释片治疗癌痛的药理特点,近年国内外将其用于癌痛治疗过程中的剂量调整,取得了很好的效果,本文对此进行综述。      

Opioid rotation from oral morphine to oral oxycodone in cancer patients with intolerable adverse effects: an open-label trial

Objective: We prospectively investigated the efficacy of opioid rotationfrom oral morphine to oral oxycodone in cancer patients whohad difficulty in continuing oral morphine treatment becauseof inadequate analgesia and/or intolerable side effects. Methods: Twenty-seven patients were enrolled and 25 were evaluated. Therate of patients who achieved adequate pain control, which providedan indication of treatment success, was evaluated as primaryendpoint. The acceptability and pharmacokinetics of oxycodonewere evaluated in addition to the assessment of analgesic efficacyand safety during the study period. Results: In spite of intense pain, the morphine daily dose could notbe increased in most patients before the study because of intolerableside effects. However, switching to oral oxycodone allowed 1.7-foldincrease as morphine equivalent dose. Consequently, 84.0% (21/25)of patients achieved adequate pain control. By the end of thestudy, all patients except one had tolerated the morphine-inducedintolerable side effects (i.e. nausea, vomiting, constipation,drowsiness). Common side effects (>10%) that occurred duringthe study were typically known for strong opioid analgesics,and most were mild to moderate in severity. A significant negativecorrelation between creatinine clearance (CCr) value and thetrough concentrations of the morphine metabolites was observed.On the other hand, no significant correlation was found betweenCCr value and the pharmacokinetic parameters of oxycodone orits metabolites. Conclusions: For patients who had difficulty in continuing oral morphinetreatment, regardless of renal function, opioid rotation tooral oxycodone may be an effective approach to alleviate intolerableside effects and pain.     

Pharmacokinetics of controlled-release oxycodone in patients with cancer pain

Oxycodone is a useful analgesic for cancer patients in pain. However, its pharmacokinetics have not been sufficiently examined and there is a lack of information, with very few reports on pharmacokinetics concerning the absorption process in particular. With this in mind, we studied the pharmacokinetics of controlled-release oxycodone (Oxy contin). We measured its serum concentration in patients with cancer pain, and calculated parameters derived using the nonlinear least-squared method program (MULTI). In the result, pharmacokinetic parameters calculated at CL/F were: 45.6+/-22.0 L/hr (Mean+/-SD), Vd/F: 473.0+/-19 6.7 L, t(1/2): 7.2+/- 6.2 hr, kel: 0.103+/-0.034, kal: 1.082+/-0.604, Lag time: 0.9 9+/-0.40 hr. In addition, the serum oxycodone concentration hardly rose until 1 hour after and just before medication, whereupon a rapid increase was evident after 1 hour. The pharmacokinetics of controlled-release oxycodone in patients with cancer pain were clarified in this study. Especially during the absorption process, the lag time was calculated specifically at about 1 hour, making it approximately equal to MS contin.     

神经妥乐平联合羟考酮控释片治疗癌性神经病理性疼痛的疗效观察

目的:探讨神经妥乐平（NTP）联合盐酸羟考酮控释片（OST）治疗癌性神经病理性疼痛（NCP ）的临床疗效。方法:将2012年8 月至2013年8 月在天津医科大学肿瘤医院疼痛治疗科接受药物治疗且VAS 评分> 4 分的102 例NCP 患者随机分成安慰剂联合OST 治疗组（A 组）和NTP 联合OST 治疗组（B 组）。 比较两组VAS 评分、疼痛缓解率、爆发痛发作次数、OST 使用剂量及药物不良反应。结果:两组患者在治疗后VAS 评分、爆发痛发作次数均较治疗前显著降低（P < 0.05）;治疗第14天后B 组VAS 评分、疼痛程度、爆发痛发作次数以及OST 日均用量均优于A 组（P < 0.05）,且B 组患者恶心、呕吐等不良反应明显少于A 组（P < 0.05）。结论:NTP 联合OST 能有效减轻NCP ,并减少OST 的用量及不良反应,值得临床进一步推广。      

盐酸羟考酮缓释片和盐酸吗啡注射液控制胰腺癌晚期癌痛的效果分析

目的:探讨盐酸羟考酮缓释片联合盐酸吗啡注射液控制胰腺癌晚期癌痛的效果。方法:选取我院2015年1月至2017年12月确诊的60例晚期胰腺癌患者，采用随机数字表法分为研究组和对照组各30例，研究组采用盐酸羟考酮缓释片联合盐酸吗啡注射液滴定，对照组采用盐酸吗啡注射液滴定；记录两组患者完成滴定所需的平均时间、疼痛控制情况、滴定治疗前与治疗后的血清前列腺素E2（PGE2）、5-羟色胺（5-HT）、组胺（HIS）、血浆P物质（SP）、β内啡肽（β-EP）及用药过程中的不良反应。结果:研究组在7天内完成盐酸吗啡注射液滴定的时间短于对照组，差异具有统计学意义（P＜0.05）；治疗7天后，研究组的疼痛控制效果优于对照组，差异具有统计学意义（P＜0.05）；治疗前，研究组和对照组的血清PGE2、5-HT、HIS、血浆SP、血浆β-EP差异不具有统计学意义（P＞0.05）；治疗后，研究组患者的血清PGE2、5-HT、HIS、血浆SP低于对照组（P＜0.05），研究组的血浆β-EP高于对照组（P＜0.05）；研究组的不良反应发生率（30.00%）与对照组（13.33%）比较，差异不具有统计学意义（P＞0.05）。结论:盐酸羟考酮缓释片联合盐酸吗啡注射液控制胰腺癌晚期癌痛效果优于单用盐酸吗啡注射液，可显著减低疼痛相关因子PGE2、5-HT、HIS、血浆SP水平。     

羟考酮缓释片联合吗啡片在重度癌痛滴定治疗中的应用

目的:对比羟考酮缓释片联合吗啡即释片与单用吗啡即释片在重度癌痛滴定中的镇痛效果、安全性及对免疫功能的影响。方法:选取2017年12月至2019年2月在我科住院的重度癌痛患者60例，按1∶1随机分为对照组（吗啡即释片滴定）与实验组（羟考酮缓释片联合吗啡即释片滴定），对比两组的疼痛缓解率、平均滴定时间、功能状态、不良反应及免疫功能。结果:滴定24小时后实验组的疼痛缓解率明显高于对照组（P<0.05），在滴定3天及1周后，两组疼痛缓解率无明显差异（P>0.05）；实验组平均滴定时间明显短于对照组（P<0.05）；滴定治疗3天后实验组功能状态评分明显高于对照组（P<0.05）；与对照组相比，实验组对细胞免疫功能抑制较轻（P<0.05）。结论:羟考酮缓释片联合吗啡即释片在重度癌痛滴定中能更快达到疼痛缓解，且对免疫功能抑制较轻。     

羟考酮联合阿片类受体拮抗剂与单独应用羟考酮处理疼痛的系统评价

目的 系统评价羟考酮联合阿片类受体拮抗剂与单独应用羟考酮处理疼痛的疗效。方法全面检索Pubmed、Embase、Cochrane图书馆及中国学术期刊全文数据库（CNKI）等数据库,收集羟考酮联合阿片类受体拮抗剂处理疼痛的随机对照试验（RCT）。制定纳入与排除标准,根据Cochrane系统评价方法对纳入的研究进行方法学质量评价,并用Review Manager 5.1软件进行Meta分析。结果 共纳入包括2003例患者在内的6项RCT。Meta分析结果显示,与单独用药组相比,联合组显著降低肠功能指数评分（MD=-13.86, 95％CI：-16.85～-10.86,P＜0.000 01）,减少便秘发生率（RR=0.70, 95％CI：0.61～0.80,P＜0.000 01）,差异均有统计学意义。两组在疼痛程度评分（MD=0.06, 95％CI：-0.17～0.29,P=0.60）、腹泻发生率（RR=1.22, 95％CI：0.79～1.89,P=0.37）、神经系统不良反应发生率（RR=1.08, 95％CI：0.88～1.32,P=0.48）以及全身性和给药部位不良反应发生率（RR=1.11, 95％CI：0.81～1.53,P=0.51）,差异均无统计学意义。结论 与单独应用羟考酮治疗疼痛相比,联合应用阿片类受体拮抗剂可以在不影响镇痛效果的情况下促进肠功能改善和降低便秘发生率,且不会增加不良反应的发生率,因而是一种较为理想的止痛方法。     

Clinical efficacy of oxycodone against cancer-related pain with a wide variety of pathophysiologies

Cancer-related pain has a wide variety of pathophysiologies. It is well known that many cancer patients suffer from visceral pain, neuropathic pain and bone pain, not only during the terminal phase but also in the active treatment phase. In general, opioids are highly effective against cancer-related pain. It is essential that opioids be selected appropriately based on the pathophysiology of pain, since the analgesic properties of opioids are not homogeneous;the sensitivities of each opioid on neuropathic pain and bone pain differ markedly. In clinical practice, it is also important that potential adverse effects of opioids are taken into account carefully. It has been demonstrated that oxycodone has favorable analgesic potency against neuropathic pain of both malignant and non-malignant origin, such as chemotherapy-induced peripheral neuropathic pain;however, we should be extremely cautious so as to avoid abuse and addiction to opioids when they are prescribed in the active treatment phase. Oxycodone could be effective on refractory bone pain that has a complicated pathophysiological mechanism. Furthermore, it has been reported that oxycodone may have a superior safety profile compared to morphine. Taking these characteristics into consideration, it appears that oxycodone is suitable as a first-line medication for the management of cancer-related pain that comes in a wide variety of pathophysiologies.