阿片类联合激素及抗惊厥药治疗晚期癌痛的临床观察

目的　探讨晚期癌痛应用阿片类药物的合理用药方案。方法　选择伴有中、重度疼痛的晚期肿瘤患者,分３组,第一组３６例,采用盐酸羟考酮控释片（奥施康定）单药治疗;第二组１９例,用奥施康定和甲强龙联合治疗;第三组２５例,用奥施康定联合加巴喷丁。观察３组患者治疗后的疼痛缓解情况和生活质量。结果　单用奥施康定组完全缓解率为６３.９％,奥施康定联合甲强龙组为６８.４％,奥施康定和加巴喷丁联用组为４８.０％。主要毒副反应为便秘,其次为恶心、呕吐。第二组毒副反应最轻,第三组部分患者出现头晕和嗜睡。结论　阿片类药物奥施康定治疗晚期癌痛具有较好的疗效,其中奥施康定联合甲强龙尤其适合肺癌伴脑转移或骨转移患者,且安全性高,值得临床推广。     

盐酸羟考酮缓释片与硫酸吗啡缓释片治疗晚期恶性肿瘤重度疼痛的比较观察

目的观察盐酸羟考酮缓释片（奥施康定）与硫酸吗啡缓释片（美施康定）治疗晚期恶性肿瘤重度疼痛的临床效果及毒副反应。方法58例晚期恶性肿瘤重度疼痛患者随机分为2组,奥施康定组30例,美施康定组28例。奥施康定起始剂量10mg·（12h）-1,美施康定起始剂量20mg·（12h）-1,根据疼痛缓解程度调整剂量,评价镇痛效果及毒副反应。结果2组患者疼痛程度均显著减轻,镇痛总有效率分别为96．7％、96．4％,比较差异无统计学意义（P〉0．05）。奥施康定组起效更快,其起效时间均为1h之内,而美施康定组起效时间为2～3h。奥施康定组的毒副反应发生率为40．0％,低于美施康定组的53．6％,差异有统计学意义（P〈0．05）。2组均无严重毒副反应发生。结论奥施康定与美施康定治疗晚期恶性肿瘤重度疼痛的临床效果相近,但奥施康定起效更快,毒副反应更轻,服用安全,是治疗晚期恶性肿瘤重度疼痛的首选药物之一。     

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。     

盐酸羟考酮缓释片与曲马多缓释片治疗中度癌痛的近期疗效比较

目的比较盐酸羟考酮缓释片（奥施康定）与曲马多缓释片（奇曼丁）治疗中度癌痛的近期疗效。方法将100例伴有中度癌痛患者随机分为奥施康定组和奇曼丁组,每组50例,分别接受奥施康定和奇曼丁的治疗。结果奥施康定组治疗后第3、7、10天的NRS评分均较奇曼丁组低,且奥施康定组治疗后第3天NRS评分下降幅度较奇曼丁组明显（P〈0.05）;奥施康定组的CR率和有效率分别为34.0%和100.0%,明显高于奇曼丁组的10.0%和84.0%（P〈0.05）;2组毒副反应发生率比较差异均无统计学意义（P〉0.05）。结论与奇曼丁相比,应用奥施康定治疗中度癌痛患者,能更快更有效缓解疼痛,而未增加毒副反应。     

超大剂量盐酸羟考酮缓释片与硫酸吗啡缓释片治疗重度癌痛的疗效及安全性比较

目的:观察超大剂量盐酸羟考酮缓释片(奥施康定)与硫酸吗啡缓释片(美施康定)治疗重度疼痛的临床疗效及安全性.方法:将重度疼痛的晚期肿瘤患者随机分为盐酸羟考酮缓释片组(奥施康定组)和硫酸吗啡缓释片(美施康定组)组,剔除观察期内(14天)两组患者中奥施康定和美施康定使用未达到超大剂量的患者.共有76例患者纳入本研究,其中奥施康定组33例,美施康定组43例.比较两组患者的止痛疗效、生活质量、不良反应.结果:奥施康定组达到首次疼痛控制稳定时间短于美施康定组,且在观察期间内,奥施康定组爆发痛发生次数以及解救药物使用剂量均少于美施康定组,差异具有统计学意义(P<0.05).奥施康定组疼痛缓解率87.88%,美施康定组疼痛缓解率83.72%,两组相比差异无统计学意义(P>0.05).奥施康定组和美施康定组治疗后生活质量较治疗前好转,差异有统计学意义(P<0.05);两组患者用药后生活质量变化比较,差异无统计学意义(P>0.05).治疗过程中,奥施康定组便秘发生情况低于美施康定组,差异具有统计学意义(P<0.05).结论:奥施康定和美施康定可有效缓解晚期癌症患者的疼痛,改善患者生活质量,具有较好的临床疗效,但盐酸羟考酮缓释片止痛快速、持久、稳定,不良反应发生率低.     

奥施康定联合塞来昔布治疗中重度癌痛的疗效分析

[目的]观察奥施康定(盐酸羟考酮)联合塞来昔布治疗中、重度癌痛的临床疗效、不良反应及患者生活质量改善情况。[方法]回顾性分析110例中、重度癌痛患者,对照组(n=57)以奥施康定5mg/12h或10mg/12h为起始剂量,按25%~50%递增剂量直至达到维持剂量;治疗组(n=53)奥施康定采用相同起始剂量,再加用塞来昔布200mg/12h,若数字分级法(NRS)评分≥4,则增加至400mg/12h,若24h内仍然NRS≥4则增加奥施康定剂量直至维持剂量(NRS<3),对比分析两组患者的疼痛缓解情况、主要不良反应、药物成瘾性以及患者生活质量的改善情况。[结果]镇痛效果相同情况下,治疗组平均维持剂量低于对照组(P=0.042),治疗组便秘的发生率较对照组明显减少(P=0.017),两组患者的生活质量均有所改善。[结论]奥施康定联合塞来昔布能有效控制中、重度癌痛,提高晚期肿瘤患者的生活质量,同时奥施康定相关的不良反应发生率也有所下降。     

奥施康定用于慢性癌性中重度疼痛的疗效观察

目的:观察奥施康定(盐酸羟考酮控释片)治疗慢性癌性中重度疼痛的疗效及不良反应.方法:对50例慢性癌性中重度疼痛患者进行治疗,其中男26例,女24例;平均年龄(54.21±12.26)岁.无重要并发症及肝肾损害,无药物滥用史.疼痛类型:主要为骨痛,其次为胸痛、腹痛、神经疼痛、髋骶部疼痛等.奥施康定剂型为10mg,由患者主诉疼痛明显时给药,且均为首次服用奥施康定.奥施康定必须整片吞服,不得掰开、咀嚼或研磨.初始剂量10mg·12h-1,服用24小时如疼痛分级下降不到1级,则第二天加量至20mg·12-1.服用24小时如疼痛分级仍下降不到1级,第三天加量至30mg·12h-1,以此类推,最多至60mg·12h-1.在用药过程中根据疼痛缓解程度调整剂量,所有患者均连续用药4周.结果:50例慢性癌性中重度疼痛患者使用的奥施康定最小剂量10mg·12h-1,最大剂量60mg·12h-1.治疗效果:完全缓解19例(38.0%).部分缓解29例(58.0%),轻度缓解2例(4.0%).其中中度疼痛患者的显效率为100.0%(7/7).重度疼痛患者的显效率为95.3%(41/43),全部患者总的显效率为96.0%(48/50).不良反应有:便秘9例,恶心呕吐6例,腹胀3例,厌食2例,嗜睡2例,头晕1例.结论:奥施康定治疗慢性癌性中重度疼痛疗效确切,有效率高,不良反应轻,服用安全.     

奥施康定治疗中重度癌痛疗效观察

目的:观察奥施康定治疗中重度癌痛的疗效及不良反应。方法:奥施康定起始剂量10mg/12h,根据疼痛缓解程度调整剂量,评价镇痛效果、KPS评分及不良反应。结果:平均镇痛起效时间41分钟,平均镇痛时间12.6h,日平均剂量69.03mg。31例中重度癌痛患者,轻度缓解1例(3.23%),中度缓解4例(12.90%),明显缓解20例(64.52%),完全缓解6例(19.53%),中度以上疼痛缓解率96.77%。KPS评分:19例(61.29%)升高,9例(29.03%)稳定,3例(9.68%)病情恶化死亡。不良反应主要为便秘11例(35.48%)。结论:奥施康定治疗中重度癌痛时,起效快,镇痛效果满意,副反应轻,服用安全。     

奥施康定治疗45例儿童重度癌痛临床疗效及安全性观察

目的:观察奥施康定治疗儿童癌痛临床疗效及安全性。方法:应用奥施康定治疗45例重度癌痛患儿,奥施康定初始剂量10mg/12h。每24h根据病情、镇痛效果进行剂量滴定一次,24h如疼痛分数下降不至3分以下(含3分),且每日突破性疼痛大于2次,则第二天加前1天剂量的25%-50%。结果:45例患者奥施康定用药最小剂量10mg/12h,最大剂量60mg/12h,中位数40mg/12h。治疗后疼痛控制总有效率为100％。主要不良反应为便秘、恶心、头昏、嗜睡、皮肤瘙痒,均为轻中度,无重度不良反应发生。结论:奥施康定对儿童癌痛镇痛效果好、毒副作用小、疗效确切、安全性高。     

小剂量奥施康定治疗晚期肺癌中度癌痛的临床疗效

目的探讨小剂量盐酸羟考酮缓释片(奥施康定)治疗晚期肺癌中度癌痛的疗效和安全性。方法将60例晚期肺癌合并中度癌痛患者随机分为对照组(30例)和治疗组(30例),对照组采用盐酸曲马多缓释片(奇曼丁,起始剂量100 mg/次、每12小时一次)治疗,治疗组采用奥施康定(起始剂量10 mg/次、每12小时一次)治疗,2组出现爆发痛时加用盐酸吗啡片滴定,次日加大剂量,直至疼痛NRS评分≤3分。至少治疗2周后评价临床疗效和不良反应。结果60例患者均可进行客观疗效评价及不良反应观察。治疗组CR 10例,PR 18例,MR 1例,NR 1例,治疗组客观有效率(RR)93.33%;对照组CR 7例,PR 20例,MR 1例,NR 2例,对照组客观有效率(RR)90.00%;与对照组相比较,治疗组的客观有效率及不良反应发生率差异无统计学意义(P>0.05),但奥施康定起效更迅速(P=0.015)、达稳态剂量更小(P<0.001)。结论小剂量奥施康定治疗晚期肺癌中度癌痛有效、安全。     

甲磺酸伊马替尼治疗晚期胃肠间质瘤的疗效及预后因素

目的:探讨口服甲磺酸伊马替尼治疗晚期胃肠间质瘤患者的疗效及预后相关因素。方法:102例复发和(或)转移性胃肠间质瘤患者接受甲磺酸伊马替尼口服治疗(起始剂量为400mg/d,病情进展者加量至600mg/d)。结果:99例患者可评价疗效,其中8例(8.1%)完全缓解,68例(68.7%)部分缓解,20例(20.2%)疾病稳定,3例(3.0%)疾病进展;客观缓解率(完全缓解+部分缓解)为76.8%。中位无进展生存期(progression-free survival,PFS)为32.0个月,1、2和3年生存率分别为96.1%、81.2%和70.8%。居住在城市、美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)体能状况(performance status,PS)<2分或客观缓解的患者有更长的PFS(P<0.05),而年龄<65岁、居住在城市、ECOG PS<2分、单纯肝转移或治疗后病灶密度降低的患者有更长的总生存期(P<0.05)。结论:口服甲磺酸伊马替尼治疗晚期胃肠间质瘤患者安全而有效。年龄、基线PS、近期疗效和治疗后病灶密度的变化是晚期胃肠间质瘤预后的重要相关因素。     

Oral ifosfamide-mesna: a clinical investigation in advanced non-small-cell lung cancer.

The purpose of this study was to evaluate the toxicity and response efficacy of fixed-dose oral ifosfamide (OI)-mesna (M) in advanced, non-small-cell lung cancer (NSCLC). OI was given in four different fractionated-dose treatment schedules with a total dose per cycle of either 3.0 g/m2, 6.0 g/m2, 7.5 g/m2 or 10 g/m2 (equivalent to a daily dose of either 750 mg, 1000 mg or 1250 mg.) M was given p.o. by drinking ampules. In the 64 patients (pts) included, a total of 305 treatment cycles were administered with no evidence of severe neurotoxicity. Twenty-two pts (37%) developed mild to moderate CNS toxicity. Neither myelosuppression, alopecia, gastrointestinal toxicity nor urotoxicity were clinical problems. On schedule 2 (6 g/m2), 3 of 14 evaluable pts (21%) had partial remissions (PR), and on schedule 3 (7.5 g/m2) 4 pts (25%) showed PRs. The median duration of response was 9 months (mts) for pts on schedule 2, and 8 mts for pts on schedule 3. We conclude that OIM can easily be tolerated in the same dose usually given intravenously (7.5 g/m2/mts), when patients at high risk for developing CNS toxicity have been previously excluded from therapy. In order to reduce CNS toxicity, it is suggested that the total dose per cycle should not exceed 7.5 g/m2 (1000 mg daily) within a fractionated-dose, 14-day treatment schedule. We further conclude that the tumor response efficacy of OIM in NSCLC is comparable to the one achieved by intravenously-administered IM, whereby the total monthly OI dose should not be less than 6.0 g/m2 (750 mg daily).     

A phase II trial of low dose administration of 5-fluorouracil and cisplatin in patients with advanced and recurrent gastric cancer.

The clinical efficacy of chemotherapy for patients with advanced gastric cancer has not been established. We investigated in a phase II study the combination chemotherapy of low dose 5-fluorouracil (5-FU) and cisplatin (low dose FP) to evaluate its clinical efficacy in terms of response, quality of life and survival in 43 gastric cancer patients including 29 advanced and 14 recurrent cases. The administration of 5-FU was done by continuous intravenous infusion for 28 consecutive days with a dose of 250 mg/m2, while the administration of cisplatin was done by 1-h intravenous drip-infusion for 5 consecutive days and 2-day intervals per week with a dose of 3.5 mg/m2, that was repeated for 4 weeks in one cycle. The response rate in advanced cases was 48.3%, evaluated in 14 cases of partial response (PR), whereas its response rate in recurrent cases was 35.7%, evaluated in 5 cases of PR. The most effective lesions for low dose FP chemotherapy were primary lesion and lymph node metastasis. The quality of life assessed by performance status and oral intake was improved in 13.8% and 37.9% of advanced cases, and 21.4% and 28.6% of recurrent cases, respectively, as compared to those of pretreatment. The median survival time and 1-year survival rate were 6 months, 21.6% in advanced cases and 10 months, 28.8% in recurrent cases, respectively. The major adverse effect was observed in gastrointestinal toxicity and leukopenia, and the all toxicities were less than grade 2, that were controllable during the treatment. These results indicated that the combination chemotherapy of low dose administration of 5-FU and cisplatin might have therapeutic efficacy in tumor response and offer improvement in quality of life in patients with advanced and recurrent gastric cancer.     

厄洛替尼对化疗失败的晚期非小细胞肺癌的疗效及安全性研究

目的：观察厄洛替尼对化疗失败的晚期非小细胞肺癌的疗效及安全性。方法：82例既往化疗失败的Ⅲ一Ⅳ期非小细胞肺癌（NSCLC）患者,均EFGR监测阳性,给予单用厄洛替尼150mg／d,服药至病情进展或出现不能耐受的不良反应,观察厄洛替尼的疗效和不良反应,对其生存期进行分析。结果：82例患者均可评价疗效,中位治疗时间为5个月（1—14个月）;客观有效率为36．5％;疾病控制率为56．1％。性别、吸烟史、Ps评分及病理类型,临床分期对疗效无统计学关联。中位肿瘤进展时间（214±26）d;中位生存期（375±21）d,1年生存率30．3％,其中肺腺癌疗效较好占30％。最常见的不良反应为皮疹（21．9％）。结论：厄洛替尼对化疗失败的中晚期非小细胞肺癌疗效确切,且不良反应轻,耐受性好。     

联合化疗方案治疗晚期胃癌的临床疗效分析和安全性评估

目的探讨联合化疗方案PDF即紫杉醇（PTX）＋顺铂（DDP）＋5-氟尿嘧啶（5-Fu）治疗晚期胃癌的临床疗效情况和安全性。方法入选2008年1月至2010年12月期间晚期胃癌患者80例,随机分为治疗组（40例）和对照组（40例）。对照组患者采用5-Fu治疗。治疗组患者采用PTX（135mg／m^2）静脉滴注3h,第1天;DDP（25mg／m^2）静脉滴注,第1—3天;5-Fu（750mg／m^2）静脉滴注,第1～5天,28天为1个化疗周期。2个周期后分析两组患者的疗效和不良反应。结果治疗组患者中,完全缓解（CR）8例,部分缓解（PR）10例,稳定（SD）15例,进展（PD）7例,临床有效率为45．0％,临床受益率为82．5％,明显高于对照组。治疗组患者的不良反应主要是骨髓抑制和消化道反应,症状较轻,不良反应明显低于对照组。结论采用联合化疗方案治疗晚期胃癌可提高疗效,且不良反应较轻,值得临床上推广。     

Oral idarubicin in patients with late chronic phase chronic myelogenous leukemia or chronic myelomonocytic leukemia

Patients with chronic myelogenous leukemia (CML) who have failed or cannot receive interferon alpha (IFN-alpha) based regimens or patients with advanced chronic myelomonocytic leukemia (CMML) have very limited current therapeutic options. Hence, there is a need to develop new strategies for these patients. This study was undertaken to determine the efficacy and toxicity of a chronic low-dose oral idarubicin regimen in these patients as positive data has been generated on this agent in shorter schedules given to patients with other hematological malignancies. Eighteen patients were treated on study. The starting dose of oral idarubicin was 2 to 5 mg/m2 daily depending in initial WBC count. This dose was escalated in the absence of Grade 4 myelosuppression or Grade 3 or 4 extramedullary toxicity. Oral idarubicin was given daily for 28 days followed by a 21 day break off treatment in repeated cycles until there was evidence of disease progression or intolerable toxicity. The dose of idarubicin was adjusted, at 2-week intervals, by 25% to maintain a white blood cell (WBC) count between 2 and 4x10(9)/L and a platelet count of >75x10(9)/L. The dose was reduced by 25% for grade 2 extramedullary toxicity and held until toxicity resolved to grade 2 or better for grade 3 toxicity. Oral idarubicin was then restarted at 75% of the initial dose. Five out of 14 CML patients achieved a complete hematologic remission. No CMML patient responded (median survival 3 months). The overall median survival was 24 months. CML patients had a median survival of 28 months. Major toxicities (myelosuppression, gastrointestinal, cardiac) were infrequent with a median cumulative dose of 1110 mg/m2 (range 54-9750). Five patients have received oral idarubicin for > 1 year with no overt cardiotoxicity, reaching median cumulative dose of 2756 mg/m2 (range 2550-9750) which is higher than those documented in prior studies. We conclude that oral idarubicin is sufficiently safe and active to warrant phase II studies investigating it as part of interferon-based regimens in patients with advanced CML.     

长春瑞滨与表阿霉素联合治疗晚期乳腺癌临床观察

目的评价长春瑞滨联合表阿霉素治疗晚期乳腺癌的疗效和毒副反应.方法长春瑞滨25 mg/m2,d1,8;表阿霉素80 mg/m2,d1,静注.结果 43例中CR 4例(9.3%),PR 21例(48.8%),SD 13例(30.2%),PD 5例(11.6%),总有效率(CR PR)58.1%.其中既往曾用CMF方案化疗的19例患者,有效率为63.2%;曾用FAC方案化疗的24例有效率为54.2%.毒副反应主要是骨髓抑制,其次是静脉炎.结论长春瑞滨联合表阿霉素治疗晚期乳腺癌有较好疗效,毒副反应可以耐受.     

A phase II trial of UFT and leucovorin in women 65 years and older with advanced breast cancer

The incidence of breast cancer increases with age. This trial evaluated the efficacy and safety of oral UFT (ftorafur plus uracil) plus leucovorin in elderly patients with advanced breast cancer. Eligibility criteria included age > or =65 years, locally advanced or metastatic breast cancer, < or =1 prior chemotherapy regimens in the setting of metastatic disease, performance status 0-2, and adequate end-organ function. UFT at 300 mg/m2 per day as 2 divided doses and 30 mg leucovorin with each dose were administered orally daily for 21 days, followed by a 7-day rest period. Ten patients were accrued. Six patients received treatment in their first relapse and 3 in their second. One patient was chemotherapy-naive. The dose-limiting toxicity was diarrhea with grade 3 or 4 diarrhea occurring more often in the oldest patients (1 of 6 patients between 65 and 69 vs. 3 of 4 patients > or =70 years old). Protocol treatment was discontinued in 2 patients (ages 78 and 83) secondary to severe gastrointestinal toxicity. One patient achieved a partial response. Although UFT/leucovorin had efficacy in 1 patient, toxicity in the patients over 70 years of age was increased. Careful evaluation of anticancer drug toxicity in very elderly patients is important as our population ages.     

Erlotinib in patients with advanced non-small-cell lung cancer: impact of dose reductions and a novel surrogate marker

Erlotinib is a relatively well-tolerated treatment option for patients with advanced non-small-cell lung cancer (NSCLC). Some patients suffer from severe skin toxicity or diarrhea, making dose reductions or even treatment cessation necessary. Recent clinical trials usually defined a 100 mg daily dose as the lowest acceptable dose, whereas little is known about the efficacy with lower doses. We retrospectively reviewed the files of all patients with advanced non-small-cell lung cancer (NSCLC) treated with erlotinib. We assessed demographic, disease- and treatment-related information. We tried to correlate tolerability with clinical efficacy. EGF receptor exon 18/19/21 mutations were analyzed in selected patients. Fifty-three patients with advanced non-small-cell lung cancer were treated with erlotinib. In nine patients (17%), the doses had to be reduced to 75 or 50 mg daily due to toxicity. We observed several sustained disease stabilizations in this subgroup. Patients suffering from paronychia with erlotinib had a significantly longer time to progression than did subjects without nail toxicity (P = 0.04). If patients were free from any toxicity, they were at high risk for early tumor progression (P = 0.001) and death. In patients with disease stabilization for 6 months or longer, we observed EGFR 18/19/21 wild type, exon 19 and exon 21 mutations. In conclusion, several patients required dose reductions during treatment with erlotinib. However, in tumors with sensitivity to erlotinib, even daily doses of 50–75 mg can result in sustained disease control. Paronychia represents a favorable surrogate marker for efficacy.