异甘草酸镁对奥沙利铂在人胃癌裸鼠模型中抗肿瘤作用的影响研究

目的:探讨异甘草酸镁对奥沙利铂在人胃癌裸鼠模型中抗肿瘤作用的影响。方法:建立人胃癌SGC-7901细胞裸鼠皮下移植瘤模型,并随机分为高、中、低剂量异甘草酸镁(Mg IG)联合奥沙利铂(L-OHP)组,单纯L-OHP组,单纯Mg IG组和葡萄糖对照组6组,连续尾静脉注射给药14 d,停药24 h后处死裸鼠,称取移植瘤质量,测量移植瘤体积,分别计算质量抑瘤率、体积抑瘤率,用TENEL法检测移植瘤组织的细胞凋亡率,并检测裸鼠肝功等指标。结果:高、中、低剂量Mg IG联合L-OHP组以及单纯L-OHP组的体积抑瘤率和质量抑瘤率均高于葡萄糖对照组,差异有统计学意义(P<0.05);各剂量Mg IG联合L-OHP组的抑瘤率高于单纯L-OHP组,且呈剂量依赖性,差异有统计学意义(P<0.05);与单纯L-OHP组相比,不同剂量Mg IG联合L-OHP组ALT和AST水平均较低,差异有统计学意义(P<0.01)。结论:异甘草酸镁对奥沙利铂的抗肿瘤作用具有协同作用,并能够潜在改善药物性肝损伤。     

雷替曲塞单药与联合奥沙利铂或伊立替康二线治疗晚期结直肠癌的临床对比观察

目的：探讨雷替曲塞单药与联合奥沙利铂或伊立替康方案二线治疗晚期结直肠癌的疗效和安全性。方法收集70例有明确病理诊断的晚期结直肠癌患者的临床资料,按化疗方案分为3组：A组（25例）：雷替曲塞2～3 mg／m2,静脉滴注,d1;B 组（22例）：奥沙利铂100～130 mg／m2,静脉滴注, d1,雷替曲塞剂量及用法同 A 组;C 组（23例）：伊立替康160～180 mg／m2,静脉滴注,d1,雷替曲塞剂量及用法同 A 组,均每3周重复,每2个周期评价疗效,最多治疗6个周期。结果70例患者均可评价疗效,A、B、C组有效率分别是4．0％（1／25）、31．8％（7／22）和21．7％（5／23）,3组疗效比较差异有统计学意义（P＜0．05）,其中A组有效率低于B、C组（P＜0．05）,B组与C组有效率比较差异无统计学意义（P＞0．05）;疾病控制率分别是52．0％（13／25）、77．2％（17／22）、73．9％（17／23）;中位无进展生存期分别是3．8个月、6．5个月、5个月;中位总生存期分别是9个月、13个月、11个月,3组比较差异均无统计学意义（P＞0．05）。最常见的毒性反应是粒细胞减少、转氨酶异常、消化道反应,以Ⅰ～Ⅱ级为主,粒细胞减少Ⅰ～Ⅱ级发生率分别为4．0％（1／25）、31．8％（7／22）、26．1％（6／23）,B、C组明显高于A组（P＜0．05）。转氨酶异常Ⅰ～Ⅱ级发生率分别为20．0％（5／25）、31．8％（7／22）、26．1％（6／23）,差异无统计学意义（P＞0．05）。腹泻Ⅰ～Ⅱ级发生率A组4．0％（1／25）、B组4．5％（1／22）低于C组34．8％（8／23）（P＜0．05）。结论雷替曲塞单药方案在晚期结直肠癌二线化疗中安全有效。雷替曲塞联合奥沙利铂或伊立替康方案疗效优于单药方案,毒性可耐受,值得临床推广应用。     

恒温在预防奥沙利铂引起的末梢神经毒性中的作用

目的 探讨恒温对预防奥沙利铂(L-OHP)化疗所致末梢神经毒性的临床效果研究。 方法 将60例使用L-OHP的患者,随机分为观察组与对照组各30例,对照组采用常规干预,观察组在常规干预基础上使用暖手宝进行恒温干预,观察4个化疗周期的末梢神经毒性程度。 结果 4个化疗周期间,观察组神经毒性症状程度均轻于对照组(Z=-2.924,P=0.003;Z=-2.360,P=0.018;Z=-3.008,P=0.003;Z=-2.133,P=0.033)。 结论 使用暖手宝可预防和减轻L-OHP化疗所致的周围神经毒性。     

Chemotherapy Alone for Patients With Stage II/III Rectal Cancer Undergoing Radical Surgery

Purpose.

The purpose of this prospective pilot study was to determine the efficacy of preoperative chemotherapy with six cycles of FOLFOX 6 (without radiation therapy) followed by radical surgery followed by six additional cycles of FOLFOX 6 for patients with stage II/III rectal cancer.

Patients and Methods.

From January 2010 to January 2014, patients with locally advanced rectal cancer who met the eligibility criteria were enrolled in this study. Patients received FOLFOX 6 chemotherapy comprising oxaliplatin and leucovorin calcium i.v. over 2 hours on day 1, then bolus, and then continuous fluorouracil i.v. over 46 hours on days 1 and 2. Treatment was repeated every 14 days for 6 courses followed by radical surgery followed by additional 6 cycles of FOLFOX 6.

Results.

In total, 45 patients were enrolled in this study. In the preoperative re-evaluation, the overall response rate was 68.8% (clinical complete response was 4.4%, and the partial response was 64.4%). There were 14 cases (31.2%) of stable disease. No patients had progressive disease. Postoperatively, the pathologic complete response rate was 8 of 45 (17.8%; 95% confidence interval [CI]: 8.9%–28.9%). The median follow-up was 29 months (range 9–54 months). The actuarial 3-year overall survival and disease-free survival rates for all patients were 80.8% (standard error, 1.877; 95% CI: 69.3%–92.3%) and 67.9% (standard error, 2.319; 95% CI: 54.3%–81.5%), respectively.

Conclusion.

Neoadjuvant chemotherapy (FOLFOX) without radiotherapy is active and safe but cannot be considered a standard of care until the results of prospective randomized phase III trials are available.

Implications for Practice:

Neoadjuvant radiotherapy of rectal cancer represents the current standard of care. However, its use is also associated with short-term toxicity and long-term morbidity. With the increasing use of total mesorectal resection resulting in better local control and advances in systemic therapy for colorectal cancer, this study highlights the question of whether radiation is a necessary component of neoadjuvant therapy for all patients with rectal cancer or whether select patients could be spared the additional toxicities and inconvenience of radiotherapy. This study suggests that neoadjuvant FOLFOX without radiotherapy is active and safe, but it could not be considered a standard of care till now.     

培美曲塞联合铂类治疗难治性晚期乳腺癌疗效与安全性分析

目的:通过观察分析培美曲塞联合铂类药物治疗晚期乳腺癌的疗效及毒副反应,探寻难治性复发转移性乳腺癌的有效治疗方法。方法:选择60例晚期乳腺癌患者,根据体质不同予以培美曲塞联合顺铂或奥沙利铂方案化疗:培美曲塞500mg/m2,第1天;顺铂75mg/m2或奥沙利铂85mg/m2,第1天;每3周一疗程,每2个疗程进行1次疗效和安全性评价。结果:60例患者均可评价疗效,中位随访14个月,PR 22例,SD 20例,RR 36.7%,中位PFS 4.5个月(95%CI:3-11个月),中位OS 8.2个月(95%CI:7.5-12个月)。主要毒副反应为疲乏,其次为白细胞减少、胃肠道反应、末梢神经炎,但均较轻微。结论:培美曲塞联合铂类方案治疗复发转移性乳腺癌疗效值得肯定,毒副反应轻微,且无论联合顺铂或奥沙利铂生存率无明显差别,患者能够耐受。     

Regorafenib plus modified FOLFOX6 as first-line treatment of metastatic colorectal cancer: A phase II trial

BackgroundThe oral multikinase inhibitor regorafenib improves overall survival (OS) in patients with metastatic colorectal cancer (CRC) for which all standard treatments have failed. This study investigated regorafenib plus modified FOLFOX (mFOLFOX6) as first-line treatment of metastatic CRC.MethodsIn this single-arm, open-label, multicentre, phase II study, patients received mFOLFOX6 on days 1 and 15, and regorafenib 160 mg orally once daily on days 4–10 and 18–24 of each 28-day cycle. The primary end-point was centrally assessed objective response rate (ORR). Secondary end-points included disease control rate (DCR), OS, progression-free survival (PFS) and safety.ResultsMedian overall treatment duration with any study drug was 9.9 months (range 0.6–19.6); median treatment duration with regorafenib was 7.7 months (range 0.1–19.5); six patients remained on regorafenib for more than 1 year. Fifty-three patients received at least one dose of regorafenib. ORR was 43.9% (all partial responses); DCR was 85.4%; median OS was not reached; median PFS was 8.5 months. Treatment-emergent adverse events were experienced by all patients but were manageable with dose modifications.ConclusionRegorafenib + mFOLFOX6 as first-line treatment in patients with metastatic CRC did not improve ORR over historical controls. Regorafenib plus mFOLFOX6 did not appear to be associated with a markedly worse tolerability profile versus mFOLFOX6 alone.ClinicalTrials.gov identifier: NCT01289821.     

A Case of Liver Fibrosis with Splenomegaly after Oxaliplatin-Based Adjuvant Chemotherapy for Colon Cancer

Previous studies reported that oxaliplatin is associated with sinusoidal obstruction syndrome. However few reports on oxaliplatin induced liver fibrosis are found in the literature. Furthermore pathogenesis of liver fibrosis is not well known. We report a case of 45-yr-old Korean man in whom liver fibrosis with splenomegaly developed after 12 cycles of oxaliplatin based adjuvant chemotherapy for colon cancer (T4N2M0). Thorough history taking and serological examination revealed no evidence of chronic liver disease. Restaging CT scans demonstrated a good response to chemotherapy. Five month after chemotherapy, he underwent right hepatectomy due to isolated metastatic lesion. The liver parenchyma showed diffuse sinusoidal dilatation and centrilobular vein fibrosis with necrosis without steatosis. We could conclude that splenomegaly was due to perisinusoidal liver fibrosis and liver cell necrosis induced portal hypertension by oxaliplatin. In addition, to investigate the pathogenesis of liver fibrosis, immunohistochemical stains such as CD31 and α-smooth muscle actin (α-SMA) were conducted with control group. The immunohistochemical stains for CD31 and α-SMA were positive along the sinusoidal space in the patient, while negative in the control group. Chemotherapy with oxaliplatin induces liver fibrosis which should be kept in mind as a serious complication.     

TNF-α联合奥沙利铂对胃癌细胞SGC-7901抑制作用的研究

目的:探讨TNF-α联合奥沙利铂对人胃癌细胞株SGC-7901生长抑制、凋亡的影响及其作用机制。方法:应用噻唑蓝(MTT)法检测不同浓度的TNF-α、奥沙利铂及两者联合应用对SGC-7901细胞抑制率;采用Hoechst检测SGC-7901细胞凋亡情况。结果:浓度为20、40、80和160μg/mL的奥沙利铂对SGC-7901的细胞生长抑制率为(29.11±0.63)%、(41.05±0.97)%、(47.69±1.03)%和(56.26±0.93)%,均可抑制细胞增殖(P<0.01);浓度为25 mg/L的TNF-α对SGC-7901细胞的生长抑制率为(2.39±0.65)%,抑制作用不明显,浓度为50、100、150 mg/L的TNF-α对SGC-7901细胞的生长抑制率为(4.51±0.86)%、(4.63±0.53)%和(4.75±1.05)%,可抑制细胞增殖(P<0.05);奥沙利铂(20μg/mL)与25、50、100和150 mg/L的TNF-α联合应用时对SGC-7901的细胞生长抑制率为(36.34±0.76)%、(45.51±0.83)%、(51.47±0.67)%和(58.78±0.97)%,与单用TNF-α(100mg/L)或奥沙利铂(20μg/mL)比较,细胞生长抑制率增加(P<0.01);Hoechst检测结果显示,单独应用100 mg/L TNF-α、单独应用20μg/mL奥沙利铂及两者联合应用均有细胞凋亡现象,且联合用药组细胞凋亡率增高(P<0.01)。结论:TNF-α可增强奥沙利铂对人SGC-7901细胞的促凋亡作用,其机制可能为TNF-α、奥沙利铂分别激活不同的Caspase,并级联和放大有关凋亡信号,因而对细胞凋亡产生了协同作用。     

替吉奥胶囊联合奥沙利铂治疗晚期胃癌的临床观察

目的观察替吉奥胶囊联合奥沙利铂治疗晚期胃癌的疗效及不良反应。方法将60例晚期胃癌患者随机分为治疗组30例和对照组30例。治疗组给予替吉奥胶囊联合奥沙利铂方案治疗,对照组给予奥沙利铂联合亚叶酸钙和5-氟尿嘧啶方案治疗,全部患者均接受至少4个周期的化疗。结果治疗组完全缓解0例,部分缓解19例,稳定10例,进展1例;对照组完全缓解0例,部分缓解9例,稳定17例,进展4例。两组主要不良反应为血液学毒性、胃肠道反应和神经系统毒性,治疗组的不良反应发生率明显低于对照组（P〈0.05）。结论替吉奥胶囊联合奥沙利铂治疗晚期胃癌安全有效。     

奥沙利铂联合贝伐单抗与卡培他滨方案治疗老年晚期胃癌疗效及安全性评估

目的：评价奥沙利铂联合贝伐单抗与卡培他滨方案治疗老年晚期胃癌的临床疗效及安全性。方法：选取高龄晚期胃癌患者136例,随机分为观察组与对照组,各68例。观察组患者采用奥沙利铂联合贝伐单抗与卡培他滨进行治疗;对照组采用5一氟尿嘧啶联合多西他赛与顺铂进行治疗,观察两组患者治疗后的生活质量、毒副反应及近期疗效。结果：经过4个疗程治疗后,观察组总有效率（88．24％）高于对照组（73．53％）,差异有统计学意义（P〈0．05）;观察组Spitzer指数高于对照组（P〈0．05）;两组糖类抗原199（CAl99）、癌胚抗原（CEA）和糖类抗原242（CA242）水平低于治疗前,观察组明显低于对照组（P〈0．05）;观察组胃肠道反应、骨髓抑制以及肝肾功能损害等不良反应的发生率均明显低于对照组（P〈0．05）。结论：贝伐单抗与卡培他滨联合奥沙利铂方案治疗晚期胃癌可以减轻化疗药物所致的消化道反应和骨髓毒性,提高机体对化疗药物的耐受性,改善患者生活质量。