Phase I study of axitinib combined with paclitaxel,docetaxel or capecitabine in patients with advanced solid tumours

Background:

Axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, enhanced the efficacy of chemotherapy in human xenograft tumour models. This phase I study investigated the safety, tolerability, pharmacokinetics and antitumour activity of axitinib combined with chemotherapy.

Methods:

A total of 42 patients with advanced solid tumours received a continuous axitinib starting dose of 5 mg twice daily (b.i.d.) plus paclitaxel (90 mg m^–2 weekly), docetaxel (100 mg m^–2 every 3 weeks) or capecitabine (1000 or 1250 mg m^–2 b.i.d., days 1–14).

Results:

Common treatment-related adverse events across all cohorts were nausea (45.2%), hypertension (45.2%), fatigue (42.9%), diarrhoea (38.1%), decreased appetite (33.3%) and hand–foot syndrome (31.0%). There was one complete response, nine partial responses and seven patients with stable disease. Ten patients (23.8%) remained on therapy for >8 months. Paclitaxel and capecitabine pharmacokinetics were similar in the absence or presence of axitinib, but docetaxel exposure was increased in the presence of axitinib. Axitinib pharmacokinetics were similar in the absence or presence of co-administered agents.

Conclusions:

Axitinib combined with paclitaxel or capecitabine was well tolerated; no additive increase in toxicities was observed. Antitumour activity was observed for each treatment regimen and across multiple tumour types.     

吉西他滨联合奥沙利铂治疗晚期非小细胞肺癌临床观察

背景与目的奥沙利铂在肺癌治疗中应用较少,本观察的目的为了解奥沙利铂联合吉西他滨治疗晚期非小细胞肺癌的疗效及毒副反应。方法对32例晚期非小细胞肺癌患者给予奥沙利铂65mg/m^2第1、8天静脉输注;吉西他滨800-1000mg/m^2,第1、8天静脉输注。21天为一个周期,完成2周期治疗后评价疗效。结果全组患者可评价疗效31例,无完全缓解,部分缓解7例,稳定15例,进展9例,总有效率22.6%,疾病控制率71.0%。中位疾病无进展生存7个月,中位生存期14.5个月。1年生存率59.0%,2年生存率45.8%。主要毒性反应为骨髓抑制和恶心呕吐。结论奥沙利铂联合吉西他滨治疗晚期非小细胞肺癌有一定疗效,可延长生存期,毒副反应可耐受,生存质量下降不明显。     

康莱特联合GP方案治疗晚期非小细胞肺癌的疗效观察

目的：观察康莱特联合GP方案治疗晚期非小细胞肺癌的临床疗效及化疗不良反应。方法：将70例患者随机分成治疗组、对照组,各35例;两组均采用GP方案：吉西他滨1000 mg/m2,第1、8天,顺铂25 mg/m2,第1-3天,3周为一周期。治疗组在此基础上于化疗第一天开始加用康莱特200ml静滴连用10天。两个周期化疗结束后比较两组临床疗效、生存质量、不良反应等情况。结果：治疗组近期疗效有效率为42.86%,对照组为34.28%,两组比较有显著性差异（P〈0.05）;治疗组KPS评分有效率为68.57%,对照组为42.86%,两组比较有显著性差异（P〈0.05）;两组主要不良反应为骨髓抑制及胃肠道反应,但治疗组的反应程度较对照组轻,两组比较有显著性差异（P〈0.05）。结论：康莱特联合化疗治疗晚期非小细胞肺癌可提高临床疗效,减轻化疗的不良反应,提高患者生存质量。     

晚期非小细胞肺癌不同治疗方案疗效的比较

目的:通过对IIIb~IV期非小细胞肺癌(NSCLC)不同化疗方案的临床疗效及毒性分析,为临床用药提供指导。方法:95例IIIb~IV期非小细胞肺癌分为4组,NP组33例,NVB25mg/m2,iv,d1,8,CDDP30mg/m2,iv,d1~3;GP组26例,GEM1000mg/m2,iv,d1,8,CBP300mg/m2,iv,d1;TP组20例,Taxotere35mg/m2,iv,d1,8,15,CBP300mg/m2,iv,d1;NG组16例,NVB25mg/m2,iv,d1,8,GEM1000mg/m2,iv,d1,8.完成2周期治疗后评价疗效。结果:临床获益率分别为75.7%,92.3%,90%,81.2%,无明显差异(P=0.77)。生活质量改善率分别为30.3%,30.8%,45%,31.3%,无明显差异(P=0.844)。毒性反应III~IV度白细胞减少,血红蛋白减少,4组无明显差别(P=0.19,P=0.096);血小板减少,4组有显著差别(P=0.013);消化道反应NP组最明显(P<0.01)。结论:NVB CDDP,GEM CBP,Taxotere CBP,GEM NVB4个方案疗效近似,毒性反应各异,临床用药应因人而异,遵循个体化用药原则。     

康莱特联合GP方案治疗晚期非小细胞肺癌的疗效观察

目的:观察康莱特联合GP方案治疗晚期非小细胞肺癌的临床疗效及化疗不良反应。方法:将70例患者随机分成治疗组、对照组,各35例;两组均采用GP方案:吉西他滨1000 mg/m2,第1、8天,顺铂25 mg/m2,第1-3天,3周为一周期。治疗组在此基础上于化疗第一天开始加用康莱特200ml静滴连用10天。两个周期化疗结束后比较两组临床疗效、生存质量、不良反应等情况。结果:治疗组近期疗效有效率为42.86%,对照组为34.28%,两组比较有显著性差异(P<0.05);治疗组KPS评分有效率为68.57%,对照组为42.86%,两组比较有显著性差异(P<0.05);两组主要不良反应为骨髓抑制及胃肠道反应,但治疗组的反应程度较对照组轻,两组比较有显著性差异(P<0.05)。结论:康莱特联合化疗治疗晚期非小细胞肺癌可提高临床疗效,减轻化疗的不良反应,提高患者生存质量。     

恩度联合化疗治疗晚期非小细胞肺癌的临床研究

目的：观察恩度（重组人血管内皮抑素）联合含铂化疗方案治疗晚期非小细胞肺癌的近期疗效和安全性,并与单纯含铂化疗方案比较。方法：依照入选标准,选择60例晚期NSCLC住院患者,分恩度联合化疗组28例和单纯化疗组32例,观察有效率（RR）、疾病控制率（DCR）、生活质量改善情况及不良反应。结果：恩度联合化疗组和单纯化疗组的有效率分别为28.57%和28.13%,无统计学差异（P〉0.05）;疾病控制率分别为96.43%和93.75%,无统计学差异（P〉0.05）。治疗后两组ECOG评分均较治疗前明显降低,具有统计学差异（P〈0.05）,但两组间比较,无统计学差异（P〉0.05）。恩度联合化疗组的临床症状缓解率较单纯化疗组高：咳嗽缓解率分别为80%和71.43%、气短缓解率分别为78.57%和75%、咯血缓解率分别为90%和81.82%、疼痛缓解率分别为75%和71.43%,但无统计学差异（P〉0.05）。两组的主要不良反应均为恶心/呕吐、疲乏及骨髓抑制,骨髓抑制以白细胞、中性粒细胞减少为主,患者均可耐受,两组间不良反应发生率均无统计学差异（P〉0.05）。结论：恩度与含铂化疗联合应用,未改善近期疗效,未增加不良反应,但具有提高生活质量的趋势,值得临床进一步研究。     

晚期肺癌患者的抑郁状态在化疗过程中的变化

目的:观察晚期肺癌患者的抑郁状态在化疗过程中的变化。方法:应用Zung’s抑郁自评量表,对可评价的111例住院的晚期肺癌患者在化疗前、中、后进行抑郁情绪的评估。结果:化疗中患者的抑郁人数比化疗前增多(P>0.05),出现Ⅲ-Ⅳ度化疗不良反应的晚期肺癌患者发生抑郁的人数较仅出现Ⅰ-Ⅱ度化疗不良反应的肺癌患者发生抑郁的人数要多(P<0.05);化疗后病情有缓解的晚期肺癌患者中的抑郁人数较化疗后病情是稳定或有进展的肺癌患者抑郁的人数要少(P<0.05)。结论:较严重的化疗不良反应有可能会增加晚期肺癌患者抑郁的发生;肿瘤病情的缓解有可能会改善晚期肺癌患者的抑郁状态。     

晚期肺癌患者的抑郁状态在化疗过程中的变化

目的：观察晚期肺癌患者的抑郁状态在化疗过程中的变化。方法：应用Zung＇s抑郁自评量表,对可评价的111例住院的晚期肺癌患者在化疗前、中、后进行抑郁情绪的评估。结果：化疗中患者的抑郁人数比化疗前增多（P〉0.05）,出现Ⅲ-Ⅳ度化疗不良反应的晚期肺癌患者发生抑郁的人数较仅出现Ⅰ-Ⅱ度化疗不良反应的肺癌患者发生抑郁的人数要多（P〈0.05）;化疗后病情有缓解的晚期肺癌患者中的抑郁人数较化疗后病情是稳定或有进展的肺癌患者抑郁的人数要少（P〈0.05）。结论：较严重的化疗不良反应有可能会增加晚期肺癌患者抑郁的发生;肿瘤病情的缓解有可能会改善晚期肺癌患者的抑郁状态。     

Phase II trial of weekly docetaxel and gemcitabine as first-line therapy for patients with advanced non-small cell lung cancer

Background A platinum doublet has been the standard treatment for patients with advanced non-small cell lung cancer (NSCLC) and good performance status. This treatment results in almost a doubling of 1-yr survival, along with an improvement in quality of life despite treatment-related toxicities. However, platinum-based treatment may be associated with significant toxicity. Materials and Methods In this trial, we prospectively evaluated a weekly regimen of docetaxel and gemcitabine for advanced NSCLC. The endpoints of this study included objective response rate, survival, and toxicity. Forty-two patients with previously untreated, advanced NSCLC with PS 0-1 were included. Patients received docetaxel (36 mg/m²) and gemcitabine (600 mg/m²) on d 1, 8, and 15 of a 28-d cycle. Responses were assessed every two cycles. The median age was 63 yr; with 22 males and 20 females; 67% were ≥60 years old; and 38 patients had stage IV disease. Results In the intent-to-treat (ITT) analysis of response, 16 patients had a partial response (38%) and 15 patients had stable disease (36%). The 1-yr survival was 48%; median survival for all patients was 11.3 mo and the median progression-free survival was 5.1 mo. Toxicities (≥grade 3) included neutropenia (29%), asthenia (26%), diarrhea (14%), thrombocytopenia (10%), pneumonitis (7%), peripheral neuropathy (5%), peripheral edema (5%), nail changes (2%), and myositis (2%). Conclusions This study demonstrated that this non-platinum doublet (docetaxel+gemcitabine) given on a weekly schedule for advanced NSCLC was well tolerated with efficacy comparable to that reported with platinum-based chemotherapy regimens.     

Phase I study of irinotecan and gemcitabine in previously untreated patients with advanced non-small cell lung cancer

BACKGROUND: Irinotecan and gemcitabine are effective against non-small cell lung cancer. We conducted a phase I study of the combined use of irinotecan and gemcitabine in previously untreated patients with advanced non-small cell lung cancer to determine dose-limiting toxicities and maximum tolerated dose. METHODS: Patients were treated with irinotecan followed by gemcitabine on days 1 and 8 every 3 weeks. Gemcitabine dose was fixed at 1000 mg/m2, and irinotecan dose was increased from 60 mg/m2. RESULTS: A total of 16 patients was enrolled. Maximum tolerated dose of irinotecan was determined up to level 3 (irinotecan 100 mg/m2). In Japan, the maximum approved weekly dose of irinotecan is 100 mg/m2, so this was the dose that was used. Only very mild hematological and non-hematological toxicities were noted. CONCLUSION: Use of 100 mg/m2 irinotecan followed by 1000 mg/m2 gemcitabine on days 1 and 8 every 3 weeks warrants a phase II study.     

贝伐珠单抗联合化疗治疗非鳞状细胞非小细胞肺癌的疗效观察

目的：观察贝伐珠单抗联合化疗治疗非鳞状细胞非小细胞肺癌的疗效和安全性.方法：回顾性分析2010年7月-2011年12月解放军总医院经组织病理学证实的局部进展或复发转移的非鳞状细胞非小细胞肺癌患者接受贝伐珠单抗联合化疗方案治疗的临床资料.贝伐珠单抗7.5mg/kg,每3周1次,联合多西他赛、培美曲塞或吉西他滨±铂类化疗.化疗2周期后按实体肿瘤疗效评价标准（RECIST）评价疗效,按美国癌症研究所制定的常见毒性判定标准（NCI-CTC） 3.0版评价不良反应.结果：21例患者中无完全缓解病例,部分缓解4例,稳定13例,进展4例,客观缓解率19.0％（4/21）,疾病控制率81.0％（17/21）,中位无疾病进展时间为7.0月,中位生存时间为10.4月.与贝伐珠单抗相关的不良反应出血6例（28.6％）,高血压1例（4.8％）,主要为Ⅰ、Ⅱ度,Ⅲ、Ⅳ度少见.结论：贝伐珠单抗联合化疗治疗进展或复发的非鳞状细胞非小细胞肺癌疗效确切,耐受性好.     

序贯放化疗治疗局部晚期非小细胞肺癌

目的评价局部晚期非小细胞肺癌予NP方案序贯放化疗综合治疗的疗效及耐受性。方法92例局部晚期非小细胞肺癌均分为两组,单纯放疗组采用常规分割放疗,原发灶及转移淋巴结总剂量均为60Gy~70Gy;综合治疗组化疗采用NP方案,先予化疗2周期,随后局部放疗,放疗方法同单放组,放疗期间停止化疗,放疗结束后继续化疗2周期。结果92例均完成治疗计划,随访1年以上。放化疗组总有效率(CR PR)65.2%,CR21.7%;均较单放组高(34.8%,10.9%)。1、2年生存率放化疗组为60.9%和32.6%,而单放组为39.1%,17.4%,两组比较有显著性差异。结论序贯放化疗治疗局部晚期非小细胞肺癌的疗效优于单纯放疗,放射性食管炎、放射性肺炎及骨髓抑制两组比较差异存在显著性,但均可耐受。     

培美曲塞二线治疗老年晚期非小细胞肺癌的临床观察

目的：探讨培美曲塞二线治疗老年晚期非小细胞肺癌的疗效及不良反应。方法：老年晚期非小细胞肺癌患者34例,采用培美曲塞500 mg/m2,静脉滴注,第1天;21d为1周期,至少2周期后评价疗效。结果：有效率（RR）为14.7%,中位TTP 3.2个月,中位生存期7.9个月。主要毒副反应为骨髓抑制及消化道反应。结论：培美曲塞二线治疗老年晚期非小细胞肺癌的近期疗效较好,且患者耐受性好,值得临床推广。     

化疗对晚期非小细胞肺癌患者凝血功能的影响

目的:探讨晚期非小细胞肺癌(NSCLC)患者化疗前后凝血指标的变化及临床意义。方法:对60例肺癌患者及20例健康人的血浆凝血酶原时间(PT)、纤维蛋白原(FIB)、部分活化凝血活酶时间(APTT)和D-二聚体(D-D))水平进行测定,同时计数血小板(PLT)。结果:化疗前肺癌患者凝血指标凝血酶原时间、纤维蛋白原、部分活化凝血活酶时间、D-二聚体、血小板与正常对照组比较有显著差异(P<0.05);肺癌患者化疗后与化疗前各项指标相比有显著性差异(P<0.05)。结论:晚期NSCLC患者普遍存在凝血功能异常,化疗可改善患者的凝血功能。     

吉非替尼联合胸腔内化疗治疗伴有恶性胸水的非小细胞肺癌的临床研究

目的:探讨吉非替尼联合胸腔内化疗治疗伴有恶性胸水的非小细胞肺癌的疗效和安全性.方法:26例伴有中、大量恶性胸水的晚期非小细胞肺癌患者,采用胸腔置管引流尽量放干胸水后,胸腔内注射化疗药物顺铂(DDP)40mg/m2、香菇多糖2mg、地塞米松10mg,从胸腔内化疗后的第3天口服吉非替尼250mg/d,直到病变进展或其他原因停药.每3个月对病灶进行1次CT检查.结果:第3个月CT复查结果显示:全组胸水控制有效率为69.2%(18/26),肿瘤病灶治疗有效率为34.6%(9/26),疾病控制率73.1%(19/26),临床受益反应为88.5%(23/26).中位疾病进展时间(TTP)为8.2个月(95%可信区间:1.8-14.2月),中位生存期(MST)为12.4个月(95%可信区间:3.1-37.4月),1年生存率为46.2%(12/26).主要不良反应是Ⅰ、Ⅱ度皮肤毒性.结论:吉非替尼联合胸腔内化疗治疗伴有恶性胸水的非小细胞肺癌具有较好的疗效和安全性.     

Phase I study of amrubicin hydrochloride and cisplatin in patients previously treated for advanced non-small cell lung cancer

OBJECTIVE: A single-center phase I trial was designed to determine both the dose-limiting toxicities and the maximum tolerated dose (MTD) for amrubicin hydrochloride in combination therapy with cisplatin for advanced non-small cell lung cancer (NSCLC) patients with prior chemotherapy. METHODS: Eligible patients received amrubicin and cisplatin on days 1 through 3 every 3 or 4 weeks. Cisplatin was administered at a fixed dosage of 20 mg/m(2) while the administered dose of amrubicin was started at 20 mg/m(2). Each group comprised 3 or 6 patients. When dose limiting toxicities were noted in three or more of six patients at a particular level, that level was estimated to be the MTD. RESULTS: Fifteen patients were enrolled in this study, including 5 males and 10 females, with a median age of 57. The dose limiting toxicities included grade 4 neutropenia which lasted 4 or more days and febrile neutropenia. The non-hematologic toxicities were well managed and rarely severe. The MTD of amrubicin in this combination regimen was estimated to be 30 mg/m(2).A partial response was observed in 4 of 15 patients (27%). CONCLUSIONS: The recommended dose was thus determined to be 25 mg/m(2) amrubicin with 20 mg/m(2) cisplatin for 3 consecutive days. A phase II study is currently underway.     

吉西他滨联合顺铂治疗不同年龄晚期非小细胞肺癌的临床观察

目的:观察不同年龄晚期非小细胞肺癌(NSCLC)患者接受吉西他滨与顺铂联合化疗时,有效率及毒副反应的差异。方法:观察我院49例接受吉西他滨与顺铂联合化疗方案的NSCLC患者,根据年龄分为≥70岁组和<70岁组,对两组患者疗效进行比较。结果:49例患者均可进行临床评价,≥70岁组和<70岁组的临床有效率分别为42.9%和40.0%;毒副反应血小板减少、恶心呕吐、乏力发生率分别为21.4%、14.3%、14.3%和11.4%、5.7%、0。结论:一般情况较好的高龄(≥70)NSCLC患者可以接受吉西他滨与顺铂联合化疗方案。     

长春瑞滨节拍化疗在晚期非小细胞肺癌患者中的应用

传统化疗依靠常规剂量静脉给药,毒性较大,肿瘤易复发和耐药,而节拍化疗低剂量、频繁、短间歇给予细胞毒性药物的治疗方式在一定程度上减少了化疗不良反应,延缓了肿瘤的复发、耐药;节拍化疗通过抗血管生成、免疫调节、抑制肿瘤干细胞并诱导肿瘤细胞休眠抑制肿瘤生长。口服长春瑞滨节拍化疗在晚期非小细胞肺癌患者治疗中有多种应用方案,包括单药化疗、双药化疗、联合抗血管生成药、联合靶向治疗、联合放疗、联合免疫治疗等多种治疗方案。     

吉西他滨联合顺铂治疗不同年龄晚期非小细胞肺癌的临床观察

目的：观察不同年龄晚期非小细胞肺癌（NSCLC）患者接受吉西他滨与顺铂联合化疗时,有效率及毒副反应的差异。方法：观察我院49例接受吉西他滨与顺铂联合化疗方案的NSCLC患者,根据年龄分为≥70岁组和〈70岁组,对两组患者疗效进行比较。结果：49例患者均可进行临床评价,≥70岁组和〈70岁组的临床有效率分别为42.9%和40.0%;毒副反应血小板减少、恶心呕吐、乏力发生率分别为21.4%、14.3%、14.3%和11.4%、5.7%、0。结论：一般情况较好的高龄（≥70）NSCLC患者可以接受吉西他滨与顺铂联合化疗方案。     

吉非替尼治疗23例晚期非小细胞肺癌

背景与目的:有临床研究表明分子靶向药物吉非替尼单药治疗NSCLC有效,本文旨在研究吉非替尼治疗晚期非小细胞肺癌的疗效及其安全性。方法:23例晚期非小细胞肺患者每日均口服吉非替尼250mg,直至患者不能耐受或病情进展时停药,观察患者症状、近期疗效、肿瘤无进展时间、生存期及不良反应。结果:23例患者至少服药1个月,其中用药后咳嗽、胸痛等症状缓解的有13例,无缓解的有3例,病情持续加重的有7例。影像学显示,肺、脑等转移灶减小的有11例(47.8%),无变化或增大的各6例(各占26.1%)。CR2例(8.7%),PR10例(43.5%),SD4例(17.4%),PD7例(30.4%)。有效率(RR)为52.2%,疾病控制率(DCR)为69.6%。患者肿瘤无进展中位时间5个月(0～15个月),至随访结束时,8例死亡,15例生存。副作用有皮疹10例(43.5%),4例(17.4%)消化道反应表现为溃疡与腹泻症状。结论:用吉非替尼治疗晚期非小细胞肺癌效果较好且安全。