伊立替康联合替吉奥二线治疗晚期胃癌临床观察

目的 观察伊立替康联合替吉奥二线治疗晚期胃癌的疗效及不良反应.方法 39例一线化疗失败的晚期胃癌患者,用伊立替康联合替吉奥方案进行二线治疗.结果 39例患者均可评价疗效,其中CR 0例,PR 14例,SD 15例,PD 10例,有效率为35.90％,疾病控制率为74.36％.主要不良反应为恶心、呕吐、腹泻、骨髓抑制等.结论 伊立替康联合替吉奥二线治疗晚期胃癌近期疗效较好,不良反应可耐受,是晚期胃癌二线治疗可选择的化疗方案.     

伊立替康联合卡培他滨治疗奥沙利铂化疗后进展的晚期结直肠癌的临床观察

目的探讨伊立替康(艾力,CPT-11)联合卡培他滨(Xeloda)治疗奥沙利铂(OXA)化疗后进展的结直肠癌的临床疗效及安全性。方法以OXA化疗失败的32例晚期结直肠癌患者为研究对象,采用伊立替康联合卡培他滨方案治疗。伊立替康100mg/m2;卡培他滨2000mg/m2·d-1,每天2次口服,共14天;每三周重复一次。观察患者的疗效及不良反应。结果 32例患者中,完全缓解(CR)2例,部分缓解(PR)16例,有效率(RR)为56.3%。不良反应主要为Ⅰ～Ⅱ度骨髓抑制、恶心呕吐、腹泻、手足综合征。结论伊立替康联合卡培他滨治疗奥沙利铂化疗后进展的结直肠癌耐受性好且疗效满意。     

伊利替康联合顺铂二线治疗晚期胃癌

目的观察伊利替康（CPT-11）联合顺铂（DDP）二线治疗晚期胃癌的疗效和不良反应。方法28例经组织学及影像学证实的晚期胃癌患者,二线按CPT-11/DDP方案化疗。具体：CPT-11 70 mg/m2 d1,8 1h静脉输注;DDP70 mg/m2 d1 2 h静脉输注,3 周为1周期。每化疗2周期后按RECIST标准评价疗效,每1周期后根据CTCAE3.0进行不良反应分级。所有患者随访30月,结果采用Kaplan-Meier进行生存分析。结果28例患者均可评价疗效,完全缓解（CR）1例(3.6%), 部分缓解（PR）11例(39.3%),疾病稳定（SD）6例(21.4%), 疾病进展（PD）10例(35.7%),有效率（CR+PR）42.9% 。中位至疾病进展时间（TTP）5月（95%［CI］,3.0～24月）,中位总生存时间（OS）8月（95%［CI］,5.0～30.0月）。3～4级血液学毒性：白细胞减少、血小板减少及贫血分别为35.7%、 25%及14.3%。3~4级非血液学毒性发生率最高的是消化道反应：恶心呕吐发生率为35.7%;腹泻发生率为17.8%。本研究中无治疗相关性死亡。结论伊利替康联合顺铂二线治疗晚期胃癌疗效显著,耐受性好。     

晚期胃癌化疗进展

随着细胞毒药物和分子靶点药物的研发,晚期胃癌患者姑息化疗取得一定进展。患者中位生存期可接近1年。本文主要介绍新药多西紫杉醇、紫杉醇、奥沙利铂、伊立替康、卡培他滨、S1及靶向药物在晚期胃癌治疗中的作用以及局部晚期胃癌的化疗策略,尤其重点介绍Ⅲ期临床试验研究结果。提出一些新联合方案,如含多西他赛的DCF方案、含奥沙利铂的EOX和FLO方案、含卡培他滨的EOX和顺铂＋希罗达方案、含伊立替康的ILF方案、含S1的S1＋DDP方案,可以作为一线治疗晚期胃癌的新的参考方案。而靶向药物在晚期胃癌治疗中结论尚不明确,其有效性、安全性和最终收益有待进一步的研究;新辅助化疗可作为局部晚期胃癌治疗的选择。     

依立替康联合顺铂二线治疗小细胞肺癌的临床观察

为观察依立替康(lrinotecan,CPT-Ⅱ)联合顺铂(DDP)二线治疗小细胞肺癌(small-cell lung cancer,SCLC)的疗效和不良反应,对22例既往经一线化疗方案治疗失败的SCLC患者采用CPT-Ⅱ 60 mg/m2,静脉滴入,d1、d8、d15;DDP 60 mg/m2,静脉滴入,d1化疗.28 d为1个周期,至少完成2个周期以上.22例患者中除1例出现Ⅳ度腹泻退出化疗,21例患者均完成所需周期化疗.其中1例CR,8例PR,有效率(CR+PR)42.9%(9/21).常见治疗毒性为乙酰胆碱综合征(9.1%,2/22)、延迟性腹泻(18.2%,4/22)、Ⅱ～Ⅲ度白细胞减少(81.8%,18/22)和Ⅱ～Ⅲ度中性粒细胞减少(72.7%,16/22)、仅1例出现Ⅳ度腹泻,主要为血液学毒性.初步研究结果提示,CPT-Ⅱ联合DDP作为二线化疗方案治疗SCLC有效,毒副反应可以耐受.     

伊立替康联合雷替曲塞二线治疗25例晚期大肠癌临床观察

大肠癌是常见的恶性肿瘤之一,发病率近年来呈上升趋势。对于复发性及转移性大肠癌,化疗仍是主要的手段之一。一线化疗方案首选FOLFOX或FOLFIRI,有效率为30%～59%,而对于一线方案失败的患者,目前尚无有效的标准方案治疗。我科对收治的48例FOLFOX方案化疗失败的晚期大肠癌患者,分别应用FOLFIRI方案(23例)和伊立替康(CPT-11)联合雷替     

奥沙利铂辅助化疗失败后一线再引入治疗晚期结直肠癌的研究

  目的  奥沙利铂辅助化疗后疾病进展的晚期结直肠癌患者优先推荐含伊立替康的方案, 然而部分患者因费用或禁忌症不能接受伊立替康的治疗。本回顾性研究探讨奥沙利铂辅助化疗失败后一线再引入治疗的疗效和安全性。  方法  奥沙利铂辅助化疗结束6个月后疾病进展一线治疗再引入的27例晚期结直肠癌患者纳入研究, 化疗方案包括mFOLFOX6和CapeOX。  结果  27例均可评价疗效, 完全缓解1例, 部分缓解7例, 稳定7例, 总有效率29.6%, 疾病控制率55.5%, 中位疾病进展时间和中位总生存分别为7.26个月(95%CI, 6.34~13.43个月)和19.1个月(95%CI, 19.3~33.1个月)。Ⅲ~Ⅳ度不良反应包括Ⅲ度粒细胞下降2例、Ⅲ度贫血1例、Ⅲ度和Ⅴ度血小板下降各1例、Ⅲ度呕吐1例、Ⅲ度口腔粘膜炎1例、Ⅲ度神经毒性2例。  结论  对于奥沙利铂辅助化疗失败后不能接受伊立替康治疗的晚期结直肠癌患者, 奥沙利铂再引入可以给患者带来生存获益, 安全可行。      

周剂量伊立替康联合雷替曲塞在晚期大肠癌二线治疗中的效果及安全性分析

目的探讨周剂量伊立替康联合雷替曲塞二线治疗晚期大肠癌的疗效及安全性。方法选取2014年3月至2016年9月间张家港澳洋医院三兴分院收治的66例晚期结直肠腺癌患者,均经过奥沙利铂与氟尿嘧啶(5-FU)(FOLFOX方案)一线治疗。按照入院先后顺利分为观察组和对照组,每组33例,观察组患者采用周剂量伊立替康联合雷替曲塞作为二线治疗方案,对照组患者采用伊立替康、5-FU和亚叶酸钙(FOLFIRI方案)治疗。评估并比较两组患者临床疗效和不良反应。结果观察组患者疾病控制率为84.8%,高于对照组患者的69.7%,差异有统计学意义(P<0.05)。观察组患者恶心呕吐和粒细胞减少Ⅲ~Ⅳ度发生率分别为21.2%和15.2%,低于对照组的36.4%和33.3%,差异均有统计学意义(均P<0.05)。结论 FOLFOX一线化疗方案治疗失败的晚期大肠癌患者,采用周剂量伊立替康联合雷替曲塞作为二线治疗方案,临床效果能够显著提高,不良反应较低,具有较好的安全性。     

非小细胞肺癌的化疗进展

NSCLC的一线治疗 伊立替康联合顺铂的疗效和不良反应以铂类为基础的两药联合方案仍是晚期NSCLC的标准化疗方案,日本Kubota等设计了4个方案比较试验(FACS),研究伊立替康联合顺铂在晚期NSCLC治疗中的作用.2000年10月～2002年6月间共入组602例,年龄20～74岁,均为病理学证实的ⅢB或Ⅳ期NSCLC,未接受过化疗,有可测量病灶,ECOG评分0/1分.     

伊立替康联合顺铂二线治疗晚期胃癌18例

目的临床观察伊立替康（CPT-11）和顺铂（DDP）联合方案用于二线治疗晚期胃癌的疗效及不良反应。方法经影像学检查及病理证实的18例晚期胃癌患者给予CPT-11180mg／m2静脉滴注90min,第1天;DDP25mg／m2静脉滴注,第1天至第3天,21d为1个治疗周期,患者最少进行2个周期化疗,采用RECIST标准进行临床效果评价。结果18例接受联合方案的患者中完全缓解（CR）0例,部分缓解（PR）6例,稳定（SD）4例,进展（PD）8例,化疗总有效率（CR＋PR）为33．3％。疾病控制率（CR＋PR＋SD）为55．6％。主要的不良反应为骨髓抑制、消化道反应、脱发、急性胆碱能综合征、迟发性腹泻,无与治疗有关的死亡。结论CPT-11和DDP联合治疗晚期胃癌具有一定的临床疗效,不良反应患者可耐受,值得进一步研究。     

A phase II study of combination therapy with oral S-1 and cisplatin in elderly patients with advanced gastric cancer

Background

A combination of S-1 and cisplatin is recognized as one of the standard first-line chemotherapy regimens for patients with advanced gastric cancer. However, demographic analyses of pivotal phase III studies have showed that only a minority of treated patients were aged 76 years or older. The purpose of this phase II study was to evaluate the safety and efficacy of combination therapy with S-1 and cisplatin in elderly patients with chemotherapy-naive advanced gastric cancer.

Methods

Patients aged 76 years or older received S-1 40 mg/m² orally twice daily for 21 days and cisplatin 60 mg/m² intravenously infused at day 8 of each 35-day cycle. Dose modification was performed according to creatinine clearance. The primary endpoint was overall survival (OS). Secondary endpoints included response rate, progression-free survival (PFS), time to treatment failure (TTF), and adverse events.

Results

A total of 40 patients were enrolled. Median OS was 12.3 months, PFS was 7.8 months, and TTF was 4.3 months. The response rate was 54%. The most common grade 3–4 adverse events were anorexia (25%), neutropenia (23%), hyponatremia (20%), anemia (18%), and febrile neutropenia (8%). No treatment-related death occurred.

Conclusions

Combination chemotherapy with S-1 and cisplatin is an effective and well-tolerated regimen for elderly patients with advanced gastric cancer when the dose is adjusted according to renal function.

     

卡培他滨联合顺铂一线治疗晚期胃癌的Ⅱ期临床研究

目的 评价卡培他滨联合顺铂一线治疗晚期胃癌的有效性和安全性.方法 对符合入组标准的141例晚期胃癌患者进行卡培他滨联合顺铂方案化疗,卡培他滨1000 mg/m2,2次/d,早、晚饭后30 min内口服,第1～14 d;顺铂20 mg/m2静脉滴注,第1～5天.21 d为1个疗程,共完成了705个周期的化疗.根据实体瘤反应评估标准(RECIST)评价疗效,根据美国国立癌症研究所抗癌药物常见不良反应评价标准(3.0版)评估不良反应.化疗结束后第1年每3个月随访1次,以后每6个月随访1次.结果 完全缓解13例,部分缓解38例,稳定54例,进展36例,总有效率为36.2%.患者中位疾病进展时间为9.0个月,中位生存时间为12.0个月.最常见的血液学毒副反应是中性粒细胞减少,有24例患者(17.0%)出现3～4级中性粒细胞减少.最常见的非血液学毒性反应是手足综合征,有35例(24.8%)出现手足综合征.本组患者无治疗相关性死亡发生.结论 卡培他滨联合顺铂一线治疗晚期胃癌具有较好的疗效,患者对此方案具有较好的耐受性,并且比5-Fu联合顺铂方案更方便,适合患者门诊应用.     

CPT-11联合5-FU/CF(FOLFIRI)化疗方案治疗晚期结直肠癌

背景与目的:CPT-11联合5-FU/CF(FOLFIRI)化疗方案是治疗晚期结直肠癌的有效方案.但是,该方案作为一线方案治疗中国晚期结直肠癌患者的资料缺乏,其疗效和安全性仍需进一步确定.本文旨在探讨FOLFIRI方案作为一线治疗方案对中国晚期结直肠癌患者的疗效和安全性.方法:自2002年1月至2005年9月期间,共54例晚期结直肠癌患者采用FOLFIRI方案作为一线方案进行治疗,回顾性分析其治疗有效率(response rate,BR)、疾病进展时间(time to progression,TTP)、总生存时间(overall survival,OS)和不良反应.结果:54例患者中52例可评价疗效.其中RR为42.6%,TTP为6个月,OS为15.2个月.最常见的不良反应为中性粒细胞减少(38.9%)、腹泻(37.1%)和恶心呕吐(50.0%),Ⅲ/Ⅳ级的发生率分别为5.6%、9.3%和9.3%,总体耐受性好.结论:FOLFIRI方案治疗中国晚期结直肠癌患者疗效肯定,作为一线化疗方案有较高的有效性,不良反应可以耐受.     

吉西他滨联合顺铂治疗晚期乳腺癌的临床观察

目的探讨吉西他滨联合顺铂方案治疗一线治疗后失败的晚期乳腺癌的临床疗效和不良反应。方法对入组的32例经病理证实的既往治疗后进展的乳腺癌患者,应用吉西他滨1000mg/m2,静滴,第1天、第8天;顺铂25mg/m2,静滴,第2～4天;联合化疗,每21天为1个周期。至少2个周期后评价疗效。结果 32例患者中,部分缓解(CR)3例(9.4%),完全缓解(PR)15例(46.9%),疾病稳定(SD)9例(28.1%),疾病进展(PD)5例(15.6%),总有效率(CR+PR)56.3%,临床获益率为84.4%。中位疾病进展时间(TTP)8.7个月。1年生存率62.5%。不良反应以骨髓抑制、消化道反应最为常见。结论应用吉西他滨联合顺铂治疗既往化疗后进展的晚期乳腺癌,疗效较好,不良反应较轻,值得临床推广应用。     

Phase II study of capecitabine and cisplatin as first-line combination therapy in patients with gastric cancer recurrent after fluoropyrimidine-based adjuvant chemotherapy

To evaluate the efficacy and safety of capecitabine and cisplatin in patients with recurrent gastric cancer after fluoropyrimidine-based adjuvant therapy. Patients with histologically confirmed and measurable advanced gastric cancer that had relapsed after fluoropyrimidine-based adjuvant chemotherapy received oral capecitabine (1250 mg m(-2) twice daily, days 1-14) and intravenous cisplatin (60 mg m(-2) over 1 h, day 1) every 3 weeks. In total, 32 patients were enrolled, of whom 30 were evaluable for efficacy and 32 for safety. A median of 5 cycles (range 1-10) was administered. One patient achieved a complete response and eight had partial responses, giving an overall response rate of 28% (95% CI, 13-44%). The median time to progression and median overall survival were 5.8 months (95% CI, 4.1-7.5 months) and 11.2 months (95% CI, 5.5-16.9 months), respectively. Grade 3 neutropenia and thrombocytopenia were observed in 38 and 6% of patients, respectively. Grade 2/3 nonhaematological toxicities included diarrhoea (19%), stomatitis (19%) and hand-foot syndrome (31%). No grade 4 toxicity, neutropenic fever or treatment-related deaths occurred. Capecitabine in combination with cisplatin was effective and well tolerated as first-line treatment in patients with recurrent gastric cancer after fluoropyrimidine-based adjuvant chemotherapy.     

Docetaxel plus cisplatin as second-line therapy in metastatic or recurrent advanced gastric cancer progressing on 5-fluorouracil-based regimen

The purpose of this study was to determine the activity and safety of docetaxel plus cisplatin as second-line chemotherapy for advanced gastric cancer. This trial included patients who had failed first-line chemotherapy with a 5-fluorouracil regimen within 1 year before their enrollment. After registration, patients were treated with docetaxel intravenously at a dose of 60 mg/m2 given over 1 hour followed by cisplatin 60 mg/m2 given over 2 hours. The treatment was continued every 3 weeks until disease progression or unacceptable toxicity was detected. Forty-three patients were registered and 41 were assessable for response. Seven partial responses were observed (17.1% of the "evaluable" patients; 95% confidence interval [CI], 0-29) with a median response duration of 3.9 months. Stable disease was documented in 2 cases (4.9%). The median survival was 5.8 months (95% CI, 3.4-8.3), resulting in a 1-year survival rate of 23%. Tolerance was acceptable, with the main toxicity being neutropenia. The authors conclude that second-line chemotherapy with docetaxel plus cisplatin for advanced gastric cancer is feasible with an acceptable toxicity level.     

Efficacy and safety of capecitabine as maintenance treatment after first-line chemotherapy using oxaliplatin and capecitabine in advanced gastric adenocarcinoma patients: a prospective observation

The value of maintenance therapy after first-line chemotherapy has been verified in lung cancer and colorectal cancer, however, in gastric cancer, the role of maintenance therapy is still waiting for an answer. The aim of this study is to evaluate the efficacy and safety of capecitabine as maintenance treatment after first-line chemotherapy in advanced gastric adenocarcinoma patients in China. Specimens of patients with advanced gastric adenocarcinoma who were given 6 cycles of oxaliplatin and capecitabine (Xelox for short) as first-line chemotherapy, without disease progression and with grade 2 or higher neuropathy, were collected for analysis. Among them, 64 patients received capecitabine as maintenance (group A) and 222 patients without maintenance as group B. Survival analysis was performed with a Cox regression model. Grades 3–4 adverse events were uncommon; hematologic toxicity was infrequent (5 %) and consistently mild in the phase of maintenance treatment. The median progression-free survival (PFS) was 11.4 months [95 % confidence interval (CI), 10.2–12.6 months] for group A patients, while it was 7.1 months (95 % CI, 6.1–8.0 months) for patients in group B, P?<?0.001. The multivariated analysis showed that the maintenance treatment was an independent prognostic factor in advanced gastric adenocarcinoma patients. The style of first-line treatment-maintenance therapy (Xelox-X) was active and feasible for advanced gastric adenocarcinoma patients who had suffered from grade 2 or higher level of neuropathy.     

Phase II study of docetaxel and cisplatin combination chemotherapy in metastatic gastric cancer

Purpose: Docetaxel, as a single agent, has demonstrated activity in patients with advanced gastric cancer and cisplatin has shown lack of overlapping toxicities with docetaxel. Therefore, we conducted a phase II study to assess the efficacy and the toxicity of a combination regimen of docetaxel plus cisplatin in patients with advanced gastric cancer who have never been treated with palliative chemotherapy. Methods: Ninety-two patients with metastatic gastric cancer were enrolled from April 2000 to March 2004. Patients with histologically confirmed gastric adenocarcinoma, at least one bi-dimensionally measurable lesion, no prior palliative chemotherapy and at least 6 months from the end of adjuvant chemotherapy were eligible for study entry. Docetaxel 75 mg/m² and cisplatin 75 mg/m² were given on day 1. The cycle was repeated every 3 weeks. The objective response was evaluated after three cycles of chemotherapy. Toxicity was assessed according to the National Cancer Institute common toxicity criteria scale version 2.0. Results: In total, 401 cycles were administered, with a median of 5 cycles per patient (range 1–9 cycles). The median age was 56 years (range 31–76). Eighty-six patients were evaluable for treatment response. The objective response rate was 43.5% (95% CI, 33.4–53.6) with one complete response and 39 partial responses. Twenty patients (21.7%) had stable disease and 26 patients (28.3%) had a progression. The median time to progression was 7.0 months (95% CI, 5.0–9.0) and the median overall survival was 11.5 months (95% CI, 9.5–13.4). The chemotherapy was generally well tolerated and the most common grade 3–4 toxicities were neutropenia (17.4%), nausea/vomiting (13.0%) and diarrhea (7.6%). Conclusion: The combination chemotherapy of docetaxel with cisplatin in advanced gastric cancer was tolerable for most patients and showed a promising antitumor activity as a first-line therapy.Keon Woo Park and Jin Seok Ahn contributed equally to this work.     

Second-line chemotherapy with irinotecan plus cisplatin after the failure of S-1 monotherapy for advanced gastric cancer

Background

For advanced gastric cancer (AGC), second-line chemotherapy after the failure of S-1 has not yet been established. The present study aimed to retrospectively evaluate the efficacy and safety of irinotecan plus cisplatin (IP) therapy after the failure of S-1 in patients with AGC.

Methods

The subjects included 87 patients with AGC who received IP therapy as second-line chemotherapy. Irinotecan (70 mg/m²) was administered by intravenous infusion followed by an intravenous infusion of cisplatin (80 mg/m²) on day 1. On day 15, irinotecan (70 mg/m²) alone was administered. The treatment was repeated every 4 weeks until disease progression, patient refusal, or severe adverse events.

Results

The median patient age was 62 years (range, 39–75 years), and the median number of treatment cycles was 3 (range, 1–9). Out of the 87 patients, 70 were assessable for clinical response. There were 2 complete responses and 18 partial responses. The overall response rate was 28.6% (95% confidence interval [CI], 18.4%–40.6%) and the disease control ratio was 70.0%. The median time to progression and median survival time from the first day of IP therapy were 4.3 months and 9.4 months, respectively. The 1-year survival rate was 34.6%. Severe (grade 3/4) leukopenia, neutropenia, anemia, and thrombocytopenia were observed in 34%, 40%, 28%, and 8% of patients, respectively. Grade 3/4 nonhematologic toxicities included anorexia (17%), febrile neutropenia (10%), diarrhea (6%), fatigue (5%), nausea (2%), and elevated creatinine (1%).

Conclusions

The combination of irinotecan plus cisplatin as second-line chemotherapy for AGC appears to be an effective and feasible treatment option after S-1 failure.     

Combination chemotherapy with paclitaxel, cisplatin and fluorouracil for patients with advanced and metastatic gastric or esophagogastric junction adenocarcinoma: a multicenter prospective study

Objective:To evaluate the efficacy and toxicity of the combination regimen of paclitaxel,cisplatin and 5-FU(PCF) as first-line or second-line therapy in patients with advanced gastric and esophagogastric junction(EGJ) adenocarcinoma in China.Methods:The patients were treated with paclitaxel 150mg/m2 on d1;fractionated cisplatin 15mg/m 2 and continuous infusion 5-FU 600mg/(m2·d) intravenously on d1-d5 of a 21-d cycle until disease progression or unacceptable toxicities.Results:Seventy-five patients have been enrolled,among which,41 received PCF regimen as the first-line therapy(group A) and 34 received the regimen as the second-line therapy(group B) with the median age of 59 years old and Karnofsky performance status(KPS) score ≥80.Toxicities were analyzed in all 75 patients.Seventy-one patients were evaluable for efficacy.The median overall survival(mOS) was 12.0 months(95% CI:7.9-16.2 months) in group A and 7.3 months(95% CI:4.3-10.3 months) in group B,respectively.The median progression-free survival(mPFS) was 5.7 months(95% CI:4.1-7.2 months) and 5.0 months(95% CI:3.1-6.9 months),respectively.The response rate(CR+PR) was 40%(16/40;95% CI:24.9-56.7%) in group A and 22.6%(7/31;95% CI:9.6-41.1%) in group B.Major grade 3 or 4 adverse events include neutropenia(41.3%),febrile neutropenia(9.3%),nausea/anorexia(10.7%),and vomiting(5.3%).There was no treatment-related death.Conclusions:The combination chemotherapy with PCF is active and tolerable as first-line and secondline therapy in Chinese patients with advanced gastric and EGJ adenocarcinoma.The response and survival of PCF are same as those of DCF,but the tolerance is much better.