经椎管内硬膜外腔介入治疗胰腺癌致顽固性癌痛的临床研究

Clinical analgesia study on epidural implantable drug delivery system compared with comprehensive medical management for abdominal intractable pain caused by cancer of pancreas

目的探讨椎管内硬膜外腔导管介入镇痛与非椎管内途径多药物联合镇痛治疗胰腺癌所致腹部顽固性癌痛的效果及不良反应。方法收集胰腺癌相关腹部顽固性癌痛患者48例,随机分为两组,非全植入式硬膜外腔导管介入镇痛组(试验组):采用硬膜外腔导管介入自控镇痛技术,经侧腹壁做皮下隧道,外接自控镇痛泵。药物联合镇痛组(对照组):采用《癌症疼痛诊疗规范(卫生部2011年版)》建议的非介入性治疗,主要为三阶梯镇痛药物的联合,包括口服、静脉、肌注、黏膜、自控镇痛(patient control analgesia,PCA)等用药方式的联合。随访3个月,以视觉模拟评分法(visual analogue scale,VAS)评估镇痛效果,记录VAS降低>20%和降低>50%的病例数,应用美国国立癌症研究院通用毒性标准(National Cancer Institute Common Toxicity Criteria,NCI-CTC)标准(纳入15项观察指标)计算药物毒性评分,记录通用毒性标准(common toxicity criteria,CTC)降低>20%的病例数,计算等效口服吗啡节俭效应,记录两组患者3个月后存活率。结果镇痛治疗4周时试验组与对照组VAS和CTC评分同时降低>20%的病例数分别为79.2%和39.1%,VAS降低>50%和CTC降低>20%的病例数分别为87.5%和34.8%;对照组VAS评分均值由7.8下降到4.8,CTC评分均值由6.8下降到5.8;试验组VAS评分均值由7.9下降到3.2,CTC评分由6.9下降到2.9;试验组和对照组等效口服吗啡节俭率分别94.5%和31.2%(P<0.01);试验组与对照组患者3个月存活率分别为79.2%和33.3%(P<0.01)。结论与非椎管内途径多药物联合镇痛比较,经椎管内硬膜外腔导管介入镇痛治疗胰腺癌所致腹部顽固性癌痛的镇痛效果更好,镇痛药相关药物不良反应降低,患者生活质量显著改善,存活时间明显延长。

Objective To evaluate the analgesia effect, drug-related toxicity, and survival of neuraxial epidural analgesia （ EPI） and nonneuraxial comprehensive medical management （ CMM） in patients with abdominal intractable pain caused by cancer of pancreas. Method Randomized controlled study of 48 abdominal intractable pancreas cancer pain patients assigned to each of two groups （ all patients had Visual Analogue Scores VAS for pain≥5/10 on at least 200 mg morphine or equivalent daily）：epidural analgesia group （ EPI,24 patients）：adopted by epidural implantable drug delivery system, doing side abdominal subcutaneous tunnel, long-term indwelling epidural catheters and external controlled analgesia pump;comprehensive medical management group （ CMM,24 patients） following standard guide-lines in management of cancer pain, adopted by non-invasive treatment, combined analgesia according the WHO＆#39;s three ladders method, including oral, intravenous, intramuscular, transdermal, PCA and other methods. For this study, measurements are reported for all patients alive at 12 weeks. The measurement point for primary objective was 2 weeks after randomization. Secondary objectives：pain scores over time （ comparison of changes in VAS for pain over the duration of the trial）;the NCI-CTC（ Common Toxicity Criteria） standardizes the comparison of drug-related ad-verse events over the duration of the follow-up period. Overall survival was represented using curves. Result At 4 weeks,19 of 24 （79. 2%） EPI patients compared with 9 of 23 （39. 1%） CMM patients achieved＆gt;20% reduction in both pain VAS and toxicity, 21 of 24 （87. 5%） EPI patients compared with 8 of 23 （34. 8 %） CMM patients a-chieved both＆gt;50% reduction in pain VAS and ＆gt;20% reduction in toxicity, at 4 weeks the EPI patients VAS pain scores decreased from 7. 9 to 3. 2 （59. 5% reduction） compared with 7. 8 to 4. 8 （38. 5% reduction） for CMM patients;the EPI patients NCI CTC scores decreased from 6. 9 to 2. 9（58. 0% reduction） compared with 6. 8 to 5. 8 （14. 7% reduction） for CMM patients . All individual VAS pain scores and drug toxicities improved with EPI at both 4 and 12 weeks than CMM. At 4 weeks,the MOED （Morphine oral equivalent dose,mg/day） was decrease 94. 5% in EPI group and 31. 2% in CMM groups（P＆lt;0. 01）. At 12 weeks, only 79. 2% of the patients randomized to EPI were a-live, compared with 33. 3% for patients in CMM groups. Conclusion EPI improved clinical success, reduced pain scores, decreased the MOED and relieved most toxicity of pain control drugs, and was associated with increased sur-vival in patients with abdominal intractable pancreas cancer pain for the duration of this 3 month trial.