阿帕替尼治疗结直肠癌1例

结直肠癌是严重威胁人类健康的恶性肿瘤之一,其发病率和死亡率均位于恶性肿瘤第3位[1],既往化疗和放疗是结直肠癌患者的主要治疗手段.近年来,随着靶向治疗的发展,无论是一线治疗、维持治疗还是疾病进展后的后续治疗,临床试验均证实在化疗基础上联合应用靶向治疗可以提高患者的总生存期(OS).现将本院收治的1例经多线治疗后应用阿帕替尼获OS延长的病例报告如下.     

阿帕替尼单药在标准方案治疗失败晚期结直肠癌患者中的疗效及安全性

目的：探讨阿帕替尼单药在标准治疗方案失败晚期结直肠癌（colorectal cancer,CRC）患者中的疗效和安全性。方法：本研究为前瞻性研究设计,用PASS15 软件计算研究所需的样本量,从2017 年7 月到2018 年8 月入组标准方案治疗失败的晚期CRC患者52 例,给予阿帕替尼起始剂量750 mg或500 mg单药治疗;评估患者的客观缓解率（ORR）和疾病控制率（DCR）,随访评价患者的无进展生存期（PFS）和总生存期（OS）,并记录治疗过程中出现的不良反应。主要研究终点为PFS,次要研究终点为ORR、DCR、OS和安全性。结果：纳入研究的52 例CRC患者中45 例可以评价疗效及安全性,其均为既往接受过至少2 次系统性化疗的晚期CRC患者。疗效：完全缓解0 例、部分缓解5 例、疾病稳定30 例、疾病进展10 例,ORR为11.11%、DCR为77.78%;预后：45 例患者的中位PFS 为3.95 个月（95% CI=3.16~4.74）,中位OS为10.3 个月（95% CI=5.70~14.90）;3 级以上不良反应：手足综合征6 例（13.33%）,高血压5 例（11.11%）,蛋白尿5 例（6.67%）,转氨酶升高4 例（8.89%）,腹泻3 例（6.67%）,疲劳2 例（4.44%）,出血1例（2.22%）。结论：阿帕替尼单药治疗标准方案失败的晚期CRC患者具有潜在的临床获益,安全性事件总体可控。     

单药阿帕替尼治疗二线及二线以上化疗失败的晚期大肠癌患者疗效分析

目的 观察阿帕替尼治疗二线及二线以上化疗失败的晚期大肠癌的临床疗效和不良反应。方法回顾性分析2016年1月至2016年11月14例Ⅳ期大肠癌患者的临床资料。所有患者均给予起始剂量为425 mg／天阿帕替尼单药治疗,并观察临床疗效及不良反应。结果14例晚期大肠癌患者中获PR 2例、SD 6例、PD 6例,有效率为14.3％,疾病控制率为57.1％。中位无进展生存时间为78天。主要不良反应为高血压、手足综合征、黏膜炎、厌食、白细胞减少、血小板减少和蛋白尿,均为1～3级。结论 单药阿帕替尼对二线及二线以上化疗失败的Ⅳ期大肠癌有较好的疗效,多数患者对425 mg／天剂量阿帕替尼的耐受良好。     

阿帕替尼联合雷替曲塞三线治疗晚期结直肠癌患者的临床疗效观察

目的探讨阿帕替尼联合雷替曲塞三线治疗晚期结直肠癌临床疗效观察。方法选取2014年5月至2017年5月间山东省淄博市第四人民医院收治的60例晚期结直肠癌患者进行回顾性分析,将采用静脉注射雷替曲塞联合阿帕替尼治疗的30例患者纳入研究组,采用静脉注射雷替曲塞治疗的30例患者纳入对照组。比较两组患者的治疗效果、不良反应及生活质量。结果治疗后研究组患者治疗总有效率为36. 7%,优于对照组患者的20. 0%,差异有统计学意义(P <0. 05)。研究组患者总生存时间和无进展生存时间均长于对照组,差异均有统计学意义(均P <0. 05)。两组患者生活质量评分比较,差异无统计学意义(P> 0. 05)。治疗后,两组患者主要的不良反应均为感觉神经毒性、肝肾功能损伤、消化道反应及血液学毒性。不良反应主要为Ⅰ～Ⅱ度,研究组患者白细胞减低发生率高于对照组,秃头发生率低于对照组,其他不良反应发生率无明显差异。结论雷替曲塞联合阿帕替尼治疗结直肠癌患者疗效较显著,可延长患者的生存时间,安全性较高。     

阿帕替尼治疗多线治疗失败后晚期乳腺癌的疗效及预后临床研究

目的 观察甲磺酸阿帕替尼单药治疗多线治疗失败的晚期乳腺癌的疗效及安全性.方法 将30例经三线及以上治疗失败后接受甲磺酸阿帕替尼治疗的晚期乳腺癌患者作为治疗组,22例经三线及以上治疗失败后接受最佳支持治疗的晚期乳腺癌患者作为对照组,比较两组患者的疗效、不良反应及预后.结果 治疗组患者总有效率及疾病控制率分别为36.7％(...     

阿帕替尼联合替莫唑胺治疗常规治疗失败的晚期黑色素瘤的疗效分析

目的 探讨阿帕替尼联合替莫唑胺治疗晚期黑色素瘤的安全性及初步疗效。 方法 收集2016年12月至2017年5月常规治疗失败的晚期黑素瘤患者9例,分为3个剂量递增组（每组3例）：替莫唑胺100 mg,阿帕替尼 250 mg;替莫唑胺 200 mg,阿帕替尼 250 mg;替莫唑胺 200 mg,阿帕替尼 500 mg。每28天重复。剂量递增采用传统3+3方法,应用RECIST 1.1标准评价疗效,不良事件按照NCI-CTCAE 4.0分级。主要研究终点为安全性（剂量限制性毒性和最大耐受剂量）,次要终点为客观有效率。 结果 9例晚期黑素瘤患者,剂量递增完成,未观察到剂量限制性毒性,常见不良反应包括高血压（33.3％）、手足皮肤反应（33.3％）、蛋白尿（22.2％）、白细胞减少（22.2％）、恶心（22.2％）、乏力（11.1％）等,均为1～2级,最大耐受剂量目前未达到。截至2017年5月,7例患者可评价疗效,1例部分缓解（PR）,4例稳定（SD）,2例进展（PD）,客观反应率为14.3％。 结论 阿帕替尼联合替莫唑胺治疗晚期黑色素瘤未观察到剂量限制性毒性,可观察到初步疗效。     

贝伐珠单抗联合化疗治疗转移性结直肠癌的近期效果及安全性

目的 研究贝伐珠单抗（bevacizumab,Bev）联合化疗治疗转移性结直肠癌的近期疗效和安全性.方法 对43例接受贝伐珠单抗联合化疗治疗的晚期结直肠癌患者进行回顾分析,评价联合治疗的近期疗效及不良反应.结果 43例患者中部分缓解（PR）17例,疾病稳定（SD）19例,疾病进展（PD）7例;中位无进展生存（PFS）为10.3个月.3～4度不良反应主要为白细胞和粒细胞减少及恶心、呕吐.与贝伐珠单抗相关的不良反应为蛋白尿、高血压、鼻出血、经血增加、肠道出血、肠穿孔及静脉血栓等.结论 贝伐珠单抗联合化疗治疗晚期结直肠癌近期疗效较好,不良反应可耐受,远期疗效有待进一步观察.     

Efficacy of chemotherapy combined with bevacizumab for metastatic colorectal cancer

Bevacizumab (BV) is widely used for patients with metastatic colorectal cancer. We investigated the efficacy and safety of chemotherapy combined with BV for metastatic colorectal cancer. From July 2007 to October 2008, 59 patients were treated by chemotherapy with BV in our hospital. Of the 47 patients who received BV in first-line therapy, 3 cases (6%) with complete response (CR), 25 cases(53%) with partial response (PR), and 17 cases (36%) with stable disease (SD) were observed. The overall response rate and tumor control rate were 60% and 96%, respectively. The median progression-free survival (PFS) was 11. 9 months, and median overall survival (OS) was 23. 6 months. There were 12 patients treated first with BV in second-line therapy. Of the 12 patients, 1 case (8%) with CR, 3 cases (25%) with PR, and 4 (33%) with SD were observed. The overall response rate and tumor control rate were 33% and 67%, respectively. The median PFS was 6.0 months and median OS was not reached. With regard to the grade 3 to 4 adverse events by NCI-CTCAE ver3.0, neutropenia was observed in more than half of the patients (56%), but a few of patients had gastrointestinal toxicities, peripheral neuropathy and infections in non-hematologic toxicities. BV-associated adverse events were hypertension, proteinuria, venous thrombosis, wound healing complication, gastrointestinal perforation and bleeding, each of which were few and not serious. Six of the patients experienced PD after first-line therapy treated with BV continuously in second-line therapy. Four of six were surviving without disease progression at the last follow-up, which suggests the effectiveness of continuation of BV. Our study showed the efficacy and safety of BV for metastatic colorectal cancer.     

Neutropaenia as a prognostic factor in metastatic colorectal cancer patients undergoing chemotherapy with first-line FOLFOX

We retrospectively analysed 153 patients with metastatic colorectal cancer who received FOLFOX with or without bevacizumab as first-line chemotherapy. Several background characteristics and chemotherapy features (grade of neutropaenia, use of bevacizumab or irinotecan, re-introduction of FOLFOX, and tumour progression) as time-varying covariates were analysed as potential prognostic factors. Of the 153 patients, mild neutropaenia (grade 1–2) occurred in 60 patients (39%) and severe neutropaenia (grade 3–4) occurred in 46 patients (30%). The other 47 patients (31%) did not experience neutropaenia. According to a multivariate Cox model with time-varying covariates, hazard ratios (HRs) of death were 0.55 (95% confidence interval (CI), 0.31–0.98; P = 0.044) for patients with mild neutropaenia and 0.35 (95% CI, 0.18–0.66; P = 0.002) for those with severe neutropaenia. Both mild and severe neutropaenia during chemotherapy are associated with improved survival in patients with MCRC. Prospective trials are required to assess whether dosing adjustments based on neutropaenia may improve chemotherapy efficacy.     

Weekly irinotecan in patients with metastatic colorectal cancer failing 5-fluorouracil-based chemotherapy: efficacy and prognostic factors

AIMS AND BACKGROUND: We evaluated the efficacy and tolerability of weekly irinotecan as a second-line treatment in patients with colorectal cancer failing 5-fluorouracil-based chemotherapy and searched for predictive and prognostic factors. METHODS: A total of 36 patients were included. Median age was 53 years (range, 33-72). One treatment cycle consisted of irinotecan, 100 mg/m2 weekly, for 4 weeks followed by a 2-week rest. Gender, age, primary site, number of metastatic sites, histologic subtype, differentiation, pretreatment CEA, CA 19-9 and lactate dehydrogenase levels and marker response to treatment were investigated as predictive factors for response to treatment and as prognostic factors in the overall survival and time to progression of the patients. RESULTS: A total of 120 cycles (median, 3 cycles) was delivered. An overall 14% objective response rate (1 complete and 4 partial responses) was achieved. The median response duration was 4 months (range, 2-7). Another 36% of the patients had stable disease for a median duration of 4 months (range, 2-8). Median time-to-disease progression was 4 months and overall median survival was 12 months (95% confidence interval, 9-15). Pretreatment serum CA 19-9 level and marker response to two courses of treatment were found to be clinically significant in time to progression and overall survival. Younger age (< or = 45 years) was a poor prognostic factor associated with a shorter time to progression. The major toxicity was grade 3-4 diarrhea, which occurred in 28% of the patients, and treatment was discontinued in 3 (8%) patients due to toxicity. Other hematological and non-hematological toxicities were mild and manageable. CONCLUSIONS: We concluded that weekly irinotecan at the dose of 100 mg/m2 is an effective and tolerable treatment option, with a 50% disease control rate, for patients with colorectal cancer failing previous 5-fluorouracil-based chemotherapy.     

Oxaliplatin and UFT combination chemotherapy in patients with metastatic colorectal cancer

A phase II study was performed to evaluate the clinical efficacy and toxicity of oxaliplatin combined with uracil and tegafur (UFT) in patients with advanced colorectal cancer previously treated with a fluoropyrimidine-based regimen. From January to December 1999, 34 patients were enrolled in this study. Patients received intravenous oxaliplatin 130 mg/m2 on day 1 and daily oral UFT 350 mg/m2 in 3 divided doses for 21 days and repeated every 21 days. Thirty-one of 34 patients were assessable for response and 32 patients for toxicity. Partial response was observed in four patients and stable disease in six patients. The response rate was 12.9% (95% CI, 3.6-29.8%) and median duration of response was 17 weeks. The median overall survival and progression-free survival of all patients were 26 weeks (range, 3-90+ weeks) and 9 weeks (range, 3-56 weeks), respectively. Sensory neuropathy was the most common toxicity, but there was no severe toxicity (>grade II) except for a case of grade III neutropenia. We conclude that oxaliplatin and UFT combination chemotherapy was well tolerated without significant toxicities. The results of this trial will serve as the basis for designing new clinical trials with a different dose or schedule.     

阿帕替尼治疗二线化疗失败的晚期卵巢癌的疗效和安全性评价

目的:评价甲磺酸阿帕替尼片治疗二线化疗失败的晚期上皮性卵巢癌患者的有效性与安全性。方法:研究共纳入20例患者,最终分析17例。入组患者口服阿帕替尼片,500 mg或250 mg 每日1次,连用28天为一个观察周期,治疗三个周期后行疗效评价。结果:治疗3个月后,PR占35.3%（6/17）,SD占11.8%（2/17）,ORR为35.3%,DCR为47.1%。起始剂量为500 mg组（ORR,30%;DCR,30%）及250 mg组（ORR,42.9%;DCR,71.4%）患者治疗效果比较无明显统计学差异。患者的中位PFS为2.2个月,中位OS为6.3个月。患者出现的最主要不良反应为高血压（70.6%）、手足综合征（52.9%）、口腔黏膜损伤（35.3%）。结论:针对二线以上化疗失败的晚期卵巢癌患者,阿帕替尼口服治疗具有一定的疗效,且安全性好,无严重不良反应。     

Efficacy of 5-fluorouracil-based chemotherapy in elderly patients with metastatic colorectal cancer: a pooled analysis of clinical trials.

BACKGROUND: Recently published population-based investigations showed elderly patients to be underrepresented in clinical trials and less often treated according to the standard therapy. Although there is evidence that elderly patients benefit from adjuvant (radio-) chemotherapy to the same extent as younger patients, no large series describes the influence of age on efficacy of chemotherapy in metastatic colorectal cancer. PATIENTS AND METHODS: We carried out a retrospective analysis using source data of 3825 patients who received 5-fluorouracil (5-FU)-containing treatment in 22 European trials and identified 629 patients with an age of > or = 70 years. RESULTS: We found an equal overall survival in elderly patients [10.8 months, 95% confidence interval (CI) 9.7-11.8] and in younger patients (11.3 months, 95% CI 10.9-11.7; P = 0.31). Response rate did not differ between age groups > or = 70 and <70 years (23.9% and 21.1%; respectively; P = 0.14). Progression-free survival was marginally prolonged in elderly patients (5.5 months, 95% CI 5.2-5.8; compared with 5.3 months, 95% CI 5.1-5.5; P = 0.01). In both age groups, infusional 5-FU resulted in significantly increased response rates, overall survival and progression-free survival compared with bolus 5-FU. CONCLUSIONS: 'Fit' elderly patients benefit at least to the same extent from palliative chemotherapy with 5-FU as younger patients. Infusional 5-FU was shown to be more effective than bolus 5-FU in both age groups. Therefore, standardized palliative chemotherapy should generally be offered to elderly patients and they should not be excluded from clinical trials.