The role of chemotherapy in microsatellite unstable (MSI-H) colorectal cancer

Introduction High-frequency microsatellite instability (MSI-H) is an alternate pathway of colorectal carcinogenesis, which accounts for 15% of all sporadic colorectal cancers. These tumours arise from mutations in the DNA mismatch repair system and thus have different responses to chemotherapeutic agents compared to microsatellite stable (MSS) cancers. Objective This review aims to summarise the available literature on the responses to chemotherapy in MSI-H colorectal cancer (CRC). Results and discussion 5 Fluorouracil (5FU) is commonly used as a chemotherapeutic agent in colon cancer and in vitro evidence shows reduced response to 5FU in MSI-H CRC. The clinical evidence is conflicting but favours a reduced response to 5FU in MSI-H CRC. Several newer agents such as COX-2 inhibitors and irinotecan are also reviewed. Conclusion Available evidence suggests that MSI-H CRC have different behaviour patterns and response to chemotherapy compared with MSS CRC.     

Efficacy of a continuous venous infusion of fluorouracil and daily divided dose cisplatin as adjuvant therapy in resectable colorectal cancer: A prospective randomized trial

PURPOSE: Daily divided dose cisplatin (DDD-P) is used as an efficient modulator of fluorouracil (5-FU), as is leucovorin (LV). We performed a randomized trial to compare the efficacy 5-FU plus DDD-P (DDD-FP) therapy with 5-FU alone in resected colorectal cancer as the adjuvant therapy. METHODS: One hundred and eighty-eight stage II or III colorectal cancer patients were enrolled. Patients were randomly assigned to receive DDD-FP (5-FU, 320 mg/ m(2), daily for 21 days; CDDP, 3.5 mg/m(2) daily for 21 days) followed by oral 5-FU (200 mg/body daily for 2 years) (DDD-FP arm) or oral 5-FU therapy (200 mg/ body daily for 2 years) exclusively (oral 5-FU arm). RESULTS: The 5-year disease-free survival (DFS) rates and the overall survival (OS) rates indicated no significant difference between the two arms. By stratified analysis, in the colon cancer patients, the DFS and the OS for the DDD-FP arm were significantly increased: 93.5% and 95.7% in the DDD-FP arm as compared with 76.9% and 82.2% in the oral 5-FU arm (P = 0.024 and P = 0.038). Regarding adverse effects, grade 3-4 toxicities were not significant in two arms. CONCLUSIONS: DDD-FP followed by oral 5-FU therapy suggested a feasible regimen for patients with resected colon cancer as the adjuvant therapy.     

基于FAERS数据库的氟尿嘧啶和卡培他滨不良事件信号挖掘研究

目的 挖掘氟尿嘧啶和卡培他滨的药物不良事件（ADE）信号,为安全用药提供参考。方法 提取FAERS数据库2017年第1季度至2021年第3季度共19个季度内上述药物的不良反应报告数据,采用报告比值比法（ROR）和综合标准法（MHRA）进行信号挖掘。结果 去重后共检出654个ADE信号,累及27个系统器官分类,其中氟尿嘧啶的ADE信号主要集中在血液及淋巴系统疾病、全身性疾病及给药部位各种反应、胃肠系统疾病和各类神经系统疾病等;卡培他滨的ADE信号主要集中在胃肠系统疾病、皮肤及皮下组织类疾病、全身性疾病及给药部位各种反应和血液及淋巴系统疾病等。在消化系统毒性方面,两种药物均显示出较强的相关性,区别在于氟尿嘧啶与血液系统毒性、心脏相关毒性关联性更强,而卡培他滨与皮肤相关毒性关联性更强。结论 检出的氟尿嘧啶和卡培他滨ADE信号中,大多数与药品说明书重合性较好,证明了本研究的可靠性。本研究还发现了药品说明书未记载的ADE,可供临床参考。     

Wirksamkeit und Nutzen eines 5‐FU‐/Salicylsäure‐haltigen Präparates in der Therapie vulgärer und plantarer Warzen – systematische Literaturübersicht und Metaanalyse

Background: 1) Salicylic acid (SA) and 5‐Fluorouracil (5‐FU) are effective drugs in wart therapy. 2) In Germany, increasing data on the benefit and the economic efficiency of drugs at Level I of evidence‐based medicine are needed. Methods: Evaluation of the effectiveness and benefits of a drug combination containing 0.5 % 5‐FU and 10 % SA in the therapy of a) common and b) plantar warts in form of a two‐step procedure – 1. Systematic literature analysis, 2. Meta‐analysis of the randomised‐controlled studies (RCTs). Results: 1. The efficacy of 5‐FU/SA therapy was tested in a total of 625 patients (n = 8 RCTs) with common warts and 101 patients (n = 4 RCTs) with plantar warts. The therapeutic effect across all studies in common warts was 63.4 % response (complete healing) for 5‐FU/SA vs. 23.1 % for the 5‐FU‐free controls, respectively. In plantar warts, the response was 63.0 % vs. 11.0 %. 2. A meta‐analysis of n = 7 RCTs on common warts (n = 325 patients) showed a mean risk difference of 0.42 (CI 0.34 – 0.50, p < 0.05), thus a significant superiority of 5‐FU/SA over SA. A comparable result was also found for plantar warts. Conclusion: The combination of 5‐FU and SA is an effective and beneficial therapy for common and plantar warts.     

ABCG2/Bcrp1可能是大鼠气管上皮干细胞的标记物

目的： 探索气管上皮干细胞的表面标记物。方法: 取2周龄的Wistar大鼠，取出气管环， 5-FU损伤12 h后，取气管上皮涂片进行增殖细胞核抗原、ABCG2/Bcrp1抗原染色、RT-PCR检测ABCG2/Bcrp1基因表达。结果: 5－FU损伤后大鼠气管上皮气管环的上皮全部脱落，残留间隔分布的裸核样细胞，基底膜完整。气管上皮涂片免疫组织化学染色可见PCNA染色阳性的细胞与阴性细胞间隔分布，间接免疫荧光染色可见ABCG2/Bcrp1阳性细胞；RT-PCR检测ABCG2/Bcrp1阳性反应产物与预计长度符合。结论: ABCG2/Bcrp1可以作为气管上皮干细胞的标记，为进一步分离纯化扩增奠定基础。     

Caspase-8在5氟尿嘧啶诱导肝癌细胞凋亡中的作用

目的探讨 5氟尿嘧啶 (5 Fu)诱导肝癌细胞凋亡与caspase 8活性变化的关系。方法采用caspase 8荧光检测试剂盒检测HepG2细胞凋亡过程中caspase 8活性变化。流式细胞仪检测加入caspase 8抑制剂IETD FMK后 5 Fu诱导的HepG2细胞凋亡百分率的变化。结果不同浓度的 5 Fu均可诱导HepG2细胞caspase 8活性升高 ,高浓度与低浓度比较差异有显著意义 (P <0 0 0 1)。肝癌细胞的caspase 8活性随 5 Fu作用时间延长而逐步升高 ,至 16h后达到高峰。IETD FMK能阻断caspase 8活化而抑制 5 Fu诱导的HepG2细胞凋亡。结论 5 Fu通过caspase 8信号传导通路诱导肝癌细胞凋亡 ;5 Fu诱导caspase 8活性升高有浓度与时间依赖性     

Outpatient-basis chemotherapy of oxaliplatin, 5-fluorouracil, and leucovorin as first-line treatment for patients with metastatic or recurrent colorectal cancer

The objectives of the present study were to evaluate the efficacy and safety of an outpatient-basis chemotherapy of oxaliplatin, 5-fluorouracil, and leucovorin as the first-line treatment for patients with advanced colorectal cancer. Forty-three histologically confirmed patients with metastatic or recurrent colorectal cancer were enrolled. The chemotherapy consisted of oxaliplatin 85 mg/m(2) as a 2-hr infusion on day 1, plus leucovorin 30 mg/m(2) over 10 min, followed by bolus 5-fluorouracil 400 mg/m(2) and an 8-hr infusion of 5-fluorouracil 600 mg/m(2) on days 1 and 2 (modified FOLFOX4), all of which were administered on an outpatient basis every 2 weeks. The median age was 58 yr (range 33-72 yr), and 25 (58.1%) patients had metastatic diseases. Eventually, 39 patients were assessable for efficacy and all assessable for toxicity. Four (9.3%) complete responses and 11 (25.6%) partial responses were confirmed, giving an overall response rate of 34.9% (95% CI; 20.0-49.7%). The median time to progression and median overall survival for all patients was 6.1 months and 17.4 months, respectively. Grade 3/4 neutropenia occurred in 2 patients (4.7%) and febrile neutropenia was observed in 1 patient (2.3%). Modified FOLFOX4, an outpatient-basis regimen, was found to be well-tolerated and effective as the first-line chemotherapy in patients with advanced colorectal cancer.     

奥沙利铂联合大剂量亚叶酸钙与氟尿嘧啶治疗晚期胃癌

目的 探讨奥沙利铂联合大剂量亚叶酸钙与氟尿嘧啶治疗晚期胃癌的疗效及其安全性。方法 晚期胃癌患者45例，采用奥沙利铂联合大剂量亚叶酸钙及氟尿嘧啶治疗，疗程3周期。结果 部分缓解18例，无变化17例，进展10例，总有效率40．0％。中位疾病进展时间5个月，1年生存率58．7％。毒性反应主要为感觉神经毒性(54．3％)，其次为恶心、呕吐和腹泻；骨髓抑制毒性小。结论 奥沙利铂联合大剂量亚叶酸钙与氟尿嘧啶方案治疗晚期胃癌，疗效肯定，患者耐受性较好。     

表柔比星,奥沙利铂和卡培他滨二线方案治疗晚期胃癌的疗效

[目的]探讨表柔比星,奥沙利铂和卡培他滨二线方案治疗晚期胃癌的临床疗效及毒副作用.[方法]对本院收治的80例胃腺癌患者在一线方案治疗后效果不佳且病情进展时给予二线方案治疗,根据患者用药方式的不同分为A组与B组,A组给予表柔比星+奥沙利铂+卡培他滨(mEXO)治疗,B组给予伊立替康+氟尿嘧啶+亚叶酸钙(FOLFIRI)治疗,比较两组患者疗效以及化疗后产生的毒副作用情况.[结果]A组治疗后疾病控制率达42.5％(17/40),B组疾病控制率达47.5％(19/40),两组相比较差异无显著性(P＞0.05);但B组患者血液毒性反应、腹泻与外周神经毒性反应Ⅰ～Ⅱ度发生率显著高于A组,且差异有显著性(P＜0.05).[结论]晚期胃癌患者经一线化疗效果不佳后,若患者还能承受二线化疗,可采用表柔比星,奥沙利铂联合卡培他滨方案化疗,且效果确切,且毒副作用较小,值得临床治疗借鉴.