癌痛规范化治疗的意义探讨

目的：探讨在癌症疼痛诊疗规范（2011年版）指导下癌痛规范化治疗的意义。方法：收集自2012年3 月至2013年12月就诊于河北医科大学第四医院肿瘤内科126 例癌痛患者的临床资料,比较NRS 评分、爆发痛次数、生存质量影响评分3 个方面改善的情况;分析不同疼痛分级、病种与治疗效果之间的关系;通过Logistic回归分析癌痛缓解的影响因素。结果：规范化治疗后NRS 评分的改善率在不同疼痛分级（P = 0.001）、不同性别患者间有显著性差异（P < 0.001）,在不同病种间无显著性差异（P = 0.112）;规范化治疗后生存质量影响总分下降和爆发痛次数减少的改善率各组内均差异无统计学意义。疼痛分级、病种对癌痛缓解情况影响不大。抗肿瘤治疗、无远处转移两个因素是促使NRS 评分、生存质量影响评分下降的独立因素;无远处转移（P = 0.046）是促使爆发痛次数减少的独立因素。结论：规范化治疗癌痛带来NRS 评分、爆发痛次数、生存质量影响评分的获益;接受抗肿瘤治疗、无远处转移的患者止痛治疗效果明显。     

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.     

Optimal pain management for patients with cancer in the modern era

Pain is a common symptom among patients with cancer. Adequate pain assessment and management are critical to improve the quality of life and health outcomes in this population. In this review, the authors provide a framework for safely and effectively managing cancer‐related pain by summarizing the evidence for the importance of controlling pain, the barriers to adequate pain management, strategies to assess and manage cancer‐related pain, how to manage pain in patients at risk of substance use disorder, and considerations when managing pain in a survivorship population. CA Cancer J Clin 2018;68:182–196 . © 2018 American Cancer Society .     

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.     

Lectin drug conjugate therapy for colorectal cancer

Drug resistance represents an obstacle in colorectal cancer (CRC) treatment because of its association with poor prognosis. rBC2LCN is a lectin isolated from Burkholderia that binds cell surface glycans that have fucose moieties. Because fucosylation is enhanced in many types of cancers, this lectin could be an efficient drug carrier if CRC cells specifically present such glycans. Therefore, we examined the therapeutic efficacy and toxicity of lectin drug conjugate therapy in CRC mouse xenograft models. The affinity of rBC2LCN for human CRC cell lines HT‐29, LoVo, LS174T, and DLD‐1 was assessed in vitro. The cytocidal efficacy of a lectin drug conjugate, rBC2LCN‐38 kDa domain of pseudomonas exotoxin A (PE38) was evaluated by MTT assay. The therapeutic effects and toxicity for each CRC cell line‐derived mouse xenograft model were compared between the intervention and control groups. LS174T and DLD‐1 cell lines showed a strong affinity for rBC2LCN. In the xenograft model, the tumor volume in the rBC2LCN‐PE38 group was significantly reduced compared with that using control treatment alone. However, the HT‐29 cell line showed weak affinity and poor therapeutic efficacy. No significant toxicities or adverse responses were observed. In conclusion, we demonstrated that rBC2LCN lectin binds CRC cells and that rBC2LCN‐PE38 significantly suppresses tumor growth in vivo. In addition, the efficacy of the drug conjugate correlated with its binding affinity for each CRC cell line. These results suggest that lectin drug conjugate therapy has potential as a novel targeted therapy for CRC cell surface glycans.     

门诊癌痛患者阿片类药物治疗全程管理的安全性评估

目的:评价门诊患者全程管理接受癌痛治疗的安全性。方法:回顾性调查分析对比癌痛病房创建前后门诊癌痛患者经全程评估,指导治疗,随访等全程管理的安全性。结果:全程管理后爆发痛的次数减少,毒副作用减轻,患者心境平和。结论:门诊癌痛患者全程管理是重要的,可指导患者正确服药,学会处理爆发痛及阿片类药物毒副作用的预防及处理,提高了阿片类药物的安全使用。     

Laxative management in ambulatory cancer patients on opioid therapy: a prospective, open-label investigation of polyethylene glycol, sodium picosulphate and lactulose

WIRZ S., NADSTAWEK J., ELSEN C., JUNKER U. & WARTENBERG H.C. (2012) European Journal of Cancer Care 21 , 131–140. Laxative management in ambulatory cancer patients on opioid therapy: a prospective, open‐label investigation of polyethylene glycol, sodium picosulphate and lactulose Constipation and the laxatives polyethylene glycol (PEG), sodium picosulphate (SPS) and lactulose (L) were investigated in outpatients with cancer and on opioid therapy. Randomly selected patients were enrolled in a prospective, controlled, open‐label trial. Endpoints were number of patients taking laxatives >28 days, number of patients with a stool‐free interval >72 h (sfi72), dosage, numerical rating scale (NRS) for constipation, and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) questionnaire scores. The 348 patients had comparable demographic and medical data. In this ambulatory population, mobility scores remained unaffected. Constipation incidence was 5.7%, with sfi72 42, mean NRS 2.3557 and mean QoL 2.1. A total of 53.2% discontinued their laxative medication. Laxative use correlated with higher opioid usage (morphine‐equivalent mg/day: no laxative 98.2, SPS 128.2, PEG 139.9, L 154.5). PEG was the most frequently prescribed laxative (PEG 27.3%, SPS 10.3%, L 9.2%). PEG (sfi72 12.6%, NRS 2.2, QoL 2.1) and SPS (sfi72 11.1%, NRS 2.7, QoL 2.2) proved more effective than L (sfi72 15.5%, NRS 3.8, QoL 2.5). In spite of opioid therapy, the incidence of constipation was low in these ambulatory cancer pain patients at an early disease stage. For prevention of constipation, PEG or SPS is recommended instead of L.     

Cancer pain management and the opioid crisis in America: How to preserve hard‐earned gains in improving the quality of cancer pain management

Cancer pain remains a feared consequence of the disease and its treatment. Although prevalent, cancer pain can usually be managed through the skillful application of pharmacologic and nonpharmacologic interventions. Unfortunately, access to these therapies has been hampered by interventions designed to contain another serious public health problem: the opioid misuse epidemic. This epidemic and the unintended consequences of efforts to control this outbreak are leading to significant barriers to the provision of cancer pain relief. Oncologists and other professionals treating those with cancer pain will require new knowledge and tools to provide safe and effective pain control while preventing additional cases of substance use disorders (SUDs), helping patients in recovery to maintain sobriety, and guiding those not yet in recovery to seek treatment. How do these 2 serious epidemics intersect and affect oncology practice? First, oncology professionals will need to adopt practices to prevent SUDs by assessing risk and providing safe pain care. Second, oncology practices are likely to see an increased number of patients with a current or past SUD, including opioid misuse. Few guidelines exist for the direct management of pain when opioids may be indicated in these individuals. Third, modified prescribing practices along with the education of patients and families are warranted to prevent the exposure of these medications to unintended persons. Finally, advocacy on behalf of those with cancer pain is imperative to avoid losing access to essential therapies, including opioids, for those who might benefit. Cancer 2018;124:2491‐7 . © 2018 American Cancer Society.     

A prospective pilot study investigating the musculoskeletal pain in postmenopausal breast cancer patients receiving aromatase inhibitor therapy

Background

Although arthralgia is a known adverse effect of aromatase inhibitor (ai) treatment in postmenopausal breast cancer patients, few studies have carried out a comprehensive evaluation of the nature, onset, and incidence of musculoskeletal (msk) pain in these patients. We therefore used a pilot study to identify conditions or markers predictive of pain.

Methods

For 24 weeks, we monitored 30 eligible postmenopausal women starting ai therapy. Pre-existing and incident msk conditions and pain were assessed clinically and with ultrasonography of the hands and wrists. In addition, patient questionnaires were used to assess pain before and during ai therapy. Biochemical markers were measured at baseline and at regular intervals after anastrozole therapy began. Gene profiling studies were carried out before and 48 hours after the initial ai administration.

Results

Over the 24-week study period, 20 participants (67%) showed no pain symptoms; 5 (17%) experienced low or moderate pain at baseline, which did not increase with ai treatment; and during therapy, 5 (17%) showed exacerbation of pain attributable to osteoarthritis of the hand and to finger flexor tenosynovitis. Although all 30 participants had some degree of msk conditions before anastrozole therapy started, the pre-existing conditions did not necessarily predispose the women to increased pain during anastrozole treatment. Higher levels of urinary N-telopeptides of type i collagen were associated with the groups presenting pain, suggesting a higher extent of pre-existing bone resorption, without significant evolution over the 24-week treatment period. Slightly higher levels of 1,25(OH)₂ vitamin D₃ were observed at baseline in patients with pain increase, but did not significantly change during treatment; however, average levels of 25(OH) vitamin D₃ increased, likely because of supplementation. Although biochemical markers did not discriminate efficiently between pain groups, a signature of 166 genes in peripheral blood mononuclear cells was identified that could stratify patients into the various groups observed in this pilot study. The gene signature was enriched in components of inflammatory signalling and chemokine expression, of antitumoural immunity pathways, and of metabolic response to hormones and xenobiotics, although no clinically significant association could be made in the present study, considering the small number of patients. Nevertheless, the observed trend suggests the feasibility of developing surrogate predictive markers of msk pain. Patient compliance was high in this study and was not affected by pain exacerbation.

Conclusions

Baseline msk assessment showed pre-existing causes for pain in most of the study patients before initiation of the ai. Exacerbation of existing osteoarthritis pain and tenosynovial symptoms was the primary cause of pain increase. Musculoskeletal pain assessment at baseline and prompt treatment of pain symptoms may help to optimize adherence to ai therapy. The value of routinely assessing inflammatory markers such as C-reactive protein and erythrocyte sedimentation rate was not supported by our pilot study. Gene expression profiles in peripheral blood mononuclear cells may be further explored in larger-scale studies as stratification markers to identify patients at risk of developing arthralgia.     

Methadone titration in opioid-resistant cancer pain

Aim: To assess the use of methadone in patients with cancer pain who fail to respond to increasing doses of other opioids or experience intolerable side-effects from them.
Method: Inpatients of a specialist palliative care unit were titrated onto oral methadone. The dose was calculated as 10% of the previous morphine equivalent dose, up to maximum of 40 mg, given every 3 h as required for analgesia. When daily requirements were stable it was divided into two regular doses. Pain was assessed on a five-point verbal rating score (VRS): a good response was defined as a fall in VRS of two points or more. Results are expressed as median (range).
Results: Thirty-three patients (13 men, 20 women, age 61 (34-91) years), 26 with inadequate analgesia and seven with intolerable opioid related side-effects, were converted to methadone from diamorphine (12), morphine (19) or fentanyl (two). Morphine equivalent dose was 480 (20-1200) mg/day prior to titration. Pain was neuropathic (11), nociceptive (three) or mixed (19). Stabilisation on methadone was complete in 3 (2-18) days in 29 (88%) patients at 80 (20-360) mg/day. Twenty-six (78%) had a good response. Four (12%) patients were withdrawn during titration (three entered terminal phase, one failed to respond). During follow-up 15 (45%) required alteration of methadone dose. Twenty-three (70%) patients were discharged home at 12 (4-26) days. In all cases the stable dose of methadone was less than the previous morphine equivalent, and there was a weak correlation between them.
Conclusions: This method of methadone titration often results in improved pain control in patients with morphine resistance or intolerance. It requires careful titration in a specialist inpatient unit as there is no reliable formula for dose equivalence.     

Impact of mood disturbance,sleep disturbance,fatigue and pain among patients receiving cancer therapy

CHENG K.K.F. & YEUNG R.M.W. (2013) European Journal of Cancer Care 22 , 70–78 Impact of mood disturbance, sleep disturbance, fatigue and pain among patients receiving cancer therapy This paper describes the prevalence of mood disturbance, sleep disturbance, fatigue and pain (MSFP), either alone or in combination in patients receiving cancer therapy, and determines its impact and whether it is a predictor for functional status and the impairment of quality of life (QoL). This is a cross-sectional study using secondary data from a sample of 214 patients being treated by chemotherapy or radiotherapy. In all, 87%, 68%, 66% and 38% of the patients reported MSFP respectively. Co-occurrence of any three and all of the four symptoms, were reported separately at rates of 29% and 31%. Patients with all four symptoms recorded significantly lower Karnofsky Performance Scale (KPS) scores (mean 77.7 ± 12.9) and QoL scores (mean subscales scores 9.0–17.6) than those with none or up to any three of the symptoms (P < 0.001). Regression of the KPS and QoL scores against the MSFP revealed an increase in the explained variance of 25%, 43%, 27%, 37% and 41% respectively for KPS, physical, emotional, functional and total QoL. The results suggest that MSFP are highly prevalent, whether alone or in combination, in patients receiving cancer therapy, and may negatively influence the patient's functional status and QoL during cancer therapy.     

静脉自控镇痛用于治疗阿片药物耐受患者伴发中重度疼痛300例观察

目的:探讨静脉自控镇痛用于治疗阿片药物耐受患者伴发中重度疼痛效果.方法:选择2014年1月至2016年6月因疼痛控制不佳而入院或转入我科的中重度癌痛患者300例,所有患者均在原所用止痛药基础上,加用静脉自控镇痛进行止痛.吗啡注射液加入自控镇痛泵,采取"背景输注+病人自控"模式输注,时间15~20分钟,常规背景输注为0.5~1 mg/h+病人自控0.5~1 mg/h.背景输注和自控剂量根据患者疼痛情况进行调整,观察患者疼痛缓解情况、生活质量评分情况及不良反应.结果:300例患者中,267例患者在3日内达到镇痛目标,总有效率为89%,NRS评分显著降低.1月后随访结果显示:229例疼痛控制仍满意,17例由于疼痛加重再次入院,12例死亡,9例患者失访.恶心呕吐、便秘、尿潴留、头晕、嗜睡等不良反应未见增加,未发生呼吸抑制和心动过缓.患者食欲、睡眠、精神、疲乏状态及日常生活能力生活质量均得到明显改善.结论:静脉自控镇痛简便、安全、有效、迅速、稳定,不良反应发生率低,显著提高生活质量,适合阿片药物耐受患者伴发中重度疼痛的治疗,值得临床推广应用.     

Fentanyl buccal tablet for the treatment of breakthrough pain in opioid‐tolerant patients with chronic cancer pain

BACKGROUND:

This study assessed the long‐term safety and tolerability of fentanyl buccal tablet (FBT) in opioid‐tolerant patients with cancer and breakthrough pain (BTP) who were either naive to FBT or had completed 1 of 2 previous double‐blind, placebo‐controlled FBT studies (rollover patients).

METHODS:

Patients who were FBT‐naive underwent titration to find a successful FBT dose. Rollover patients used a previously identified successful dose of FBT. Patients who achieved a successful dose were eligible to enter a maintenance phase (≥12 months). Safety assessments included adverse events (AEs), physical and neurologic examinations, and clinical laboratory tests.

RESULTS:

Two hundred thirty‐two patients were enrolled. A total of 112 entered titration; 79 identified a successful FBT dose, and 77 of these patients entered the maintenance phase along with 120 rollover patients (n = 197). AEs resulted in discontinuation of therapy for 33% of patients. The most common AEs were generally typical of opioids administered to cancer patients. All serious AEs were considered to be related to the patients' underlying conditions, except for 1 incident of FBT‐related drug withdrawal syndrome. Sixty patients died after enrollment because of disease progression. Fifteen (6%) patients experienced ≥1 application‐site AE, all of which were considered by investigators to be related to FBT.

CONCLUSIONS:

FBT was generally well tolerated and had a favorable safety profile in the long‐term (≥12 months) management of patients with persistent cancer pain and BTP. No unexpected AEs occurred. Safety and tolerability was similar to that observed in short‐term studies. Cancer 2009. © 2009 American Cancer Society.