Gabapentin mitigates neuropathic pain in cancer patients--a case report

A 64-year-old male underwent low anterior resection of the rectum for rectal cancer. Five years later, he suffered neuropathic cancer pain on the left-posterior surface of his thigh caused by sacral invasion of the recurrence site. His neuropathic pain was not sufficiently responsive to the combination therapy of opioids, non-steroidal antiinflammatory drugs (NSAIDs), continuous infusion of subcutaneous ketamine and oral mexiletine. Gabapentin, which has been suggested as an adjuvant analgesic for neuropathic pain introduced orally, rapidly and significantly alleviated his pain and we could subsequently dispense with ketamine and mexiletine. No adverse effect was seen during this treatment. The present case indicates that gabapentin would be one of the most effective adjuvant analgesics for neuropathic cancer pain.     

Acetaminophen (paracetamol) improves pain and well-being in people with advanced cancer already receiving a strong opioid regimen: a randomized, double-blind, placebo-controlled cross-over trial.

PURPOSE: To determine whether adding regular acetaminophen (paracetamol) could improve pain and well-being in people with advanced cancer and pain despite strong opioids. PATIENTS AND METHODS: Participants took acetaminophen for 48 hours and placebo for 48 hours. The order (acetaminophen or placebo first) was randomly allocated. Pain was the primary outcome. Preferences, number of opioid breakthrough doses, overall well-being, nausea and vomiting, drowsiness, constipation, and cold sweats were secondary outcomes. Patients rated themselves daily with visual analog scales (VAS) and a verbal numeric scale (VNS) for pain, all scaled from 0 to 10. RESULTS: Thirty patients completed the trial. The oral opioid was morphine in 23 patients and hydromorphone in seven patients. The median daily opioid dose in oral morphine equivalents was 200 mg (range, 20 to 2,100 mg). Nonsteroidal anti-inflammatory drugs, corticosteroids, or both were used by 16 patients. Pain and overall well-being were better for patients receiving acetaminophen than for those receiving placebo. The mean difference was 0.4 (95% CI, 0.1 to 0.8; P =.03) in VNS for pain, 0.6 (95% CI, -0.1 to 1.3; P =.09) in VAS for pain, and 0.7 (95% CI, 0.0 to 1.4; P =.05) in VAS for overall well-being. More patients preferred the period they took acetaminophen (n = 14) than the period they took placebo (n = 8), but many had no preference (n = 8). There were no differences in the other outcomes. CONCLUSION: Acetaminophen improved pain and well-being without major side effects in patients with cancer and persistent pain despite a strong opioid regimen. Its addition is worth considering in all such patients.     

盐酸羟考酮控释片联合加巴喷丁治疗晚期癌症神经病理性疼痛疗效分析

目的:探讨盐酸羟考酮控释片联合加巴喷丁治疗晚期癌症神经病理性疼痛的疗效.方法:晚期癌症的神经病理性疼痛患者,通过视觉模拟划线法(VAS)和口头叙述法(VRS)分级进行疼痛强度评估,分为A组盐酸羟考酮控释片20例,B组盐酸羟考酮控释片+加巴喷丁20例,通过个体化用药,研究其治疗疼痛缓解度,有效率.结果:A组轻度疼痛9例,无痛6例,有效率为75.0％,B组轻度疼痛5例,无痛13例,有效率为90.0％.结论:盐酸羟考酮控释片+加巴喷丁治疗晚期癌症神经病理性疼痛疗效显著.     

A randomized, controlled, double-blinded clinical trial of gabapentin 300 versus 900?mg versus placebo for anxiety symptoms in breast cancer survivors

Gabapentin is used for the treatment of hot flashes and neuropathic pain in breast cancer survivors, and is commonly used off-label for the treatment of anxiety. Yet, clinical trial evidence to support the use of gabapentin for anxiety symptoms is lacking. In a randomized, double-blinded controlled trial we compared 300?mg gabapentin versus 900?mg gabapentin versus placebo. Subjects were 420 breast cancer patients who had completed all chemotherapy cycles. Anxiety traits and current (state) anxiety were measured using the Speilberger Strait-Trait Anxiety Inventory at baseline, 4 and 8?weeks. Pain was measured at baseline using a 10-point scale. Analyses included analysis of covariance and ordinary least squares regression. At 4?weeks, state anxiety change scores were significantly better for gabapentin 300 and 900?mg (p?=?0.005) compared to placebo. The magnitude of improvement was proportional to baseline state anxiety. At 8?weeks, the anxiolytic effects of gabapentin compared to placebo persisted (p?<?0.005). We found no significant interactions. The lower dose (300 mg) was associated with the best treatment outcomes for all patients except those with the highest baseline anxiety. Given its similar pharmacology, efficacy in the treatment of hot flashes, and low cost, gabapentin may provide a low cost and parsimonious alternative treatment choice for breast cancer survivors presenting in primary care practices with anxiety symptoms. Gabapentin is effective for hot flashes, and, therefore, may provide therapeutic benefit for both anxiety and hot flashes at a generic drug price. For patients reluctant to take a controlled substance, such as a benzodiazepine, gabapentin may offer an alternative therapy. Similarly, patients with a history of substance use may benefit from gabapentin without risk of addiction or abuse. For cancer survivors experiencing both hot flashes and anxiety, gabapentin may provide a single effective treatment for both and is an alternative therapy for anxiety for patients unwilling to take a benzodiazepine or those with a history of substance use.     

Oxycodone and pregabalin using transdermal fentanyl patch provided relief of symptoms for postherpetic neuropathic pain in a patient with non-small cell lung cancer

This paper presents a man in his 70's with non-small cell lung cancer (cT3N2M0, Stage III A) after chemoradiation therapy during follow-up visits. He was referred to the department of palliative care 1 month after the occurrence of herpes zoster, because of pain. Opioids (transdermal fentanyl patch and rapid-release oxycodone) were administered for his cancer pain previously. Additionally, gabapentin was given for neuropathic pain uncontrolled by opioids. However, this was replaced by pregabalin because he experienced somnolence. Although numbing improved remarkably with pregabalin, the pain was only slightly improved. The dose of rapid-release oxycodone was increased and controlled-release oxycodone was added. This provided for marked pain relief. We conclude that administration of pregabalin as an analgesic adjuvant, and oxycodone, which is an opioid, should be considered in the treatment of cancer patients without improvement of neuropathic pain from herpes zoster through use of the transdermal fentanyl patch.     

大剂量阿片类药物治疗癌性疼痛回顾性分析

目的：观察大剂量阿片类止痛药物控制国人癌性疼痛的疗效及安全性。方法：八一医院肿瘤内科２００５年１月～２００９年２月住院治疗晚期恶性肿瘤患者中,有２１例因重度疼痛而需要大剂量阿片类（口服吗啡等效剂量为≥３００ｍｇ／ｄ）治疗,回顾性分析其临床诊断,阿片类滴定时间、剂量、使用持续时间以及毒副反应。结果：２１例中,１６例为胃肠道肿瘤;１４例存在骨骼转移,８例有腹膜后淋巴结转移;躯体痛１４例,神经性疼痛和内脏痛各９例。治疗过程中１７例患者经历阿片类转换。滴定至最大剂量的时间为４～３７８ｄ（中位时间９２ｄ）。最大剂量范围为３３０ｄ～１２００ｍｇ／ｄ（中位数４５０ｍｇ／ｄ）。大剂量阿片类持续时间为１２～２５５ｄ（中位时间６１ｄ）。出现疼痛后生存期为２～４５个月（中位数１１个月）。未出现威胁生命的毒副反应。结论：大剂量阿片类止痛药对具有重度疼痛的国人晚期肿瘤患者是安全有效的。     

Gabapentin for the treatment of pain syndrome related to radiation‐induced mucositis in patients with head and neck cancer treated with concurrent chemoradiotherapy

BACKGROUND:

This retrospective study evaluated the efficacy of gabapentin for the treatment of pain syndromes related to radiation‐induced mucositis in patients with head and neck cancers treated with concurrent chemoradiation.

METHODS:

Data from 42 patients with head and neck malignancies treated with concurrent chemoradiotherapy using an intensity‐modulated radiotherapy technique were analyzed. Gabapentin was initiated in the second week of radiotherapy. Opiates were prescribed in addition to gabapentin as clinically indicated to obtain adequate pain control.

RESULTS:

At a median dose of 2700 mg/day of gabapentin, only 33% and 55% of patients required additional low‐dose narcotic medications for pain control during the third and fourth week of treatment, respectively, despite exhibiting a grade 2 or higher mucositis in 71% and 86% of the patients, respectively. Furthermore, during the last weeks of treatment, 71% of the patients required additional low‐dose opiates for adequate pain control, despite the presence of grade 2 or higher mucositis in 95% and 100% of patients at Weeks 5 and 6, respectively. Only 1 patient had a treatment‐related interruption of >3 days during chemoradiotherapy.

CONCLUSIONS:

Gabapentin appears to be promising in reducing the need for high total doses of opioids and avoiding unplanned treatment interruptions for patients with head and neck malignancies treated with concurrent chemoradiotherapy and should be further evaluated prospectively in controlled clinical trials. Cancer 2010. © 2010 American Cancer Society.     

盐酸羟考酮控释片联合加巴喷丁治疗晚期癌症神经病理懒疗效分析

目的：探讨盐酸羟考酮控释片联合加巴喷丁治疗晚期癌症神经病理性疼痛的疗效。方法：晚期癌症的神经病理性疼痛患者,通过视觉模拟划线法（VAS）和口头叙述法（VRs）分级进行疼痛强度评估,分为A组盐酸羟考酮控释片20例,B组盐酸羟考酮控释片＋加巴喷丁20例,通过个体化用药,研究其洛疗疼痛缓解度,有效率。结果：A组轻度疼痛9例,无痛6例,有效率为75．0％,B组轻度疼痛5例,无痛13例,有效率为90．0％。结论：盐酸羟考酮控释片＋加巴喷丁治疗晚期癌症神经病理性疼痛疗效显著。     

A prospective open-label trial of gabapentin as an adjuvant analgesic with opioids for Japanese patients with neuropathic cancer pain

Background  

Neuropathic pain is regarded as one of the main causes of cancer pain refractory to standard opioid therapy in palliative care. The use of adjuvant analgesics for neuropathic cancer pain is largely empirical and the true efficacy of these adjuvant analgesics has been unknown. Gabapentin is one of the new promising anticonvulsant drugs as an adjuvant analgesic for neuropathic cancer pain.     

Suramin therapy for patients with symptomatic hormone-refractory prostate cancer: results of a randomized phase III trial comparing suramin plus hydrocortisone to placebo plus hydrocortisone.

PURPOSE: Suramin is a novel agent that has demonstrated preliminary evidence of antitumor activity in hormone-refractory prostate cancer (HRPC). A prospective randomized clinical trial was designed to evaluate pain and opioid analgesic intake as surrogates for antitumor response in HRPC patients with significant, opioid analgesic-dependent pain. PATIENTS AND METHODS: A double-blind, placebo-controlled trial randomized patients to receive a 78-day, outpatient regimen of either suramin plus hydrocortisone (HC, 40 mg/d) or placebo plus HC. Treatment assignment was unblinded when either disease progression or dose-limiting toxicity occurred; placebo patients were allowed to cross-over to open-label suramin plus HC. In addition to pain and opioid analgesic intake, prostate-specific antigen (PSA) response, time to disease progression, quality of life, performance status, and survival were compared. RESULTS: Overall mean reductions in combined pain and opioid analgesic intake were greater for suramin plus HC (rank sum P =.0001). Pain response was achieved in a higher proportion of patients receiving suramin than placebo (43% v 28%; P =.001), and duration of response was longer for suramin responders (median, 240 v 69 days; P =.0027). Time to disease progression was longer (relative risk = 1.5; 95% confidence interval, 1.2 to 1.9) and the proportion of patients with a greater than 50% decline in PSA was higher (33% v 16%; P =.01) in patients who received suramin. Neither quality of life nor performance status was decreased by suramin treatment, and overall survival was similar. Most adverse events were of mild or moderate intensity and were easily managed medically. CONCLUSION: Outpatient treatment with suramin plus HC is well tolerated and provides moderate palliative benefit and delay in disease progression for patients with symptomatic HRPC.     

恶性肿瘤患者临终前的阿片类药物止痛回顾

目的:调查恶性肿瘤患者临终前的阿片类药物止痛治疗现状。方法:分析242例患者阿片类药物止痛的基本情况,比较不同性别、年龄及肿瘤原发灶的阿片止痛情况。结果:176例(72.73%)用阿片止痛,其中134例(76.14%)用美施康定,28例(15.91%)用多瑞吉,14例(7.95%)用弱阿片,无阿片过量引起的死亡。日平均吗啡口服剂量:男性(166.67mg)明显高于女性(107.66mg),年龄增大,用量逐渐减小,但无显著差异,不同原发灶的患者无显著差异。结论:止痛治疗合理、安全;男性止痛所需阿片量比女性大,年龄大的患者阿片用量较小,肿瘤原发灶与阿片止痛剂量无关。     

Determinants of Opioid Efficiency in Cancer Pain: a Comprehensive Multivariate Analysis from a Tertiary Cancer Centre

Background: Pain is one of the most terrifying symptoms for cancer patients. Although most patients withcancer pain need opioids, complete relief of pain is hard to achieve. This study investigated the factors influencingpersistent pain-free survival (PPFS) and opioid efficiency. Materials and Methods: A prospective study wasconducted on 100 patients with cancer pain, hospitalized at the medical oncology clinic of Akdeniz University.Patient records were collected including patient demographics, the disease, treatment characteristics, and detailsof opioid usage. Pain intensity was measured using a patient self-reported visual analogue scale (VAS). The areaunder the curve (AUC) reflecting the pain load was calculated from daily VAS tables. PPFS, the primary measureof opioid efficacy, was described as the duration for which a patient reported a greater than or equal to two-pointdecline in their VAS for pain. Predictors of opioid efficacy were analysed using a multivariate analysis. Results:In the multivariate analysis, PPFS was associated with the AUC for pain (Exp (B)=0.39 (0.23-0.67), P=0.001),the cumulative opioid dosage used during hospitalisation (Exp (B)=1.00(0.99-1.00), P=0.003) and changes in theopioid dosage (Exp (B)=1.01 (1.00-1.01), P=0.016). The change in VAS score over the standard dosage of opioidswas strongly associated with current cancer treatment (chemotherapy vs. others) (ß=-0.31, T=-2.81, P=0.007)and the VAS for pain at the time of hospitalisation (ß=-0.34, T=-3.07, P= 0.003). Conclusions: The pain load,opioid dosage, concurrent usage of chemotherapy and initial pain intensity correlate with the benefit receivedfrom opioids in cancer patients.     

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临床效果评价

目的 探讨癌性神经病理性疼痛患者使用神经妥乐平+羟考酮控释片治疗后的临床效果.方法 选取VAS评分＞4分的癌性神经病理性疼痛患者86例,并按数字表法随机分为对照组与试验组两组,每组均43例.对照组予以安慰剂+羟考酮控释片的治疗方案,试验组则实施神经妥平乐+羟考酮控释片的治疗措施.分析对比两组患者治疗前后VAS评分、SAS评分、治疗后疼痛缓解情况、治疗7d及14 d后爆发痛发作情况及羟考酮控释片服用情况.结果 经过治疗后,试验组患者VAS评分为(0.96±1.08)分、SAS评分为(36.69 ±8.45)分,均明显低于对照组的(3.01±1.29)分、(48.56±10.27)分,差异有统计学意义(P＜0.05);试验组患者整体疼痛缓解情况明显优于对照组,疼痛缓解率(95.35％)明显高于对照组的(53.49％),组间对比有统计学上有意义(P＜0.05);治疗14 d时,试验组爆发痛发作次数为(1.72±0.95)次/d、羟考酮控释片日均服用量为(80.76±20.79) mg/d,均明显优于对照组[(2.21±1.24)次/d、(101.99±23.56)mg/d],有统计学意义(P＜0.05).结论 神经妥乐平联合羟考酮控释片联合治疗,可缓解肿瘤患者的癌性神经病理性疼痛,临床治疗效果较优.     

氢溴酸高乌甲素联合阿片类药治疗中重度神经病理性癌痛疗效观察

目的探讨氢溴酸高乌甲素联合阿片类药与单独应用阿片药治疗中重度神经病理性癌痛的疗效差别。方法2003年1月至2007年12月间我院肿瘤科收治了63例神经病理性癌疼痛患者,Karnofsky评分50～80分,随机分为两组,其中A组采用氢溴酸高乌甲素联合阿片类镇痛药（32例）;B组单用阿片类镇痛药（31例）;疼痛评估采用视觉模拟评分法（visual analogue scale,VAS）,分析第0、3、10天的变化;评价两组阿片药品的消耗量以及不良反应的发生率。结果A、B组的VAS评分基线值差异无显著性（P=0.452）。从疼痛的缓解程度来看,VAS评分下降程度A组要好于B组,差异有显著性（P〈0.05）;从阿片类药物的消耗来看,B组明显要多于A组;阿片不良反应B组多于A组（P=0.015）。结论氢溴酸高乌甲素联合阿片类药可以更好地治疗患者神经病理性癌痛,减少了阿片药品的用量,降低了因为阿片药带来的不良反应,是治疗中重度神经病理性癌痛安全有效的办法。     

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.     

Controversies in pharmacotherapy of pain management

Since the establishment of the WHO three-step ladder for management of cancer pain, several controversies have arisen, which are partly due to new drug development, reformulations of older analgesics, and technological advancements. As a result, clinicians need clarification of several questions. Is morphine the opioid of choice for moderate to severe pain in cancer? Should combinations of opioids be used? When should spinal opioids be used to treat pain in cancer? What are the appropriate opioid doses for breakthrough pain? Should selective cyclo-oxygenase (COX) 2 inhibitors be used? What is the best tactic to treat neuropathic pain, and what first-line adjuvant analgesic should be used? And do bisphosphonates relieve bone pain in cancers other than breast cancer and myeloma? This review addresses these questions.     

Potential Role of Bupropion Sustained Release for Cancer-Related Fatigue: a Double-Blind,Placebo-Controlled Study

Background: Cancer-related fatigue (CRF) is very common and can be experienced at all stages of disease and insurvivors. CRF causes patients more distress than pain or nausea and vomiting. Different pharmacologic interventionshave been evaluated for the management of CRF. The purpose of this study was to determine the efficacy of bupropionsustained release (SR) as a treatment for fatigue in patients with cancer. Methods: In this randomized, double-blind,placebo-controlled trial, patients with fatigue due to cancer were randomly assigned to either 150mg daily of bupropionSR or matching placebo. The primary endpoint was the changes in average daily fatigue from baseline to week 4 usingthe Functional Assessment of Chronic Illness-therapy- Fatigue (FACIT-F) questionnaire. Results: 40 patients wererandomly assigned to treatment with bupropion SR or placebo (20 in each group). Analysis of covariance (ANCOVA)showed a significant improvement in fatigue and quality of life in the bupropion group compared to baseline (P=0.000).Secondary outcome, including depression, severity of fatigue and performance status didn’t show significant differencebetween groups. Generally, bupropion SR was tolerated well. Conclusion: Four weeks of 150 mg bupropion SRimprove fatigue significantly in cancer patients. Bupropion has potential as an effective and safe pharmaceutical agentfor treating CRF.     

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。     

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.     

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。