Safety and Efficacy of Hyperthermic Intraperitoneal Chemoperfusion with High-Dose Oxaliplatin in Patients with Peritoneal Carcinomatosis

Background Cytoreduction with hyperthermic intraperitoneal chemoperfusion (HIPEC) has an established role in selected patients with peritoneal carcinomatosis (PC). We analyzed the safety and efficacy of HIPEC using high-dose oxaliplatin, a cytotoxic agent commonly used in metastatic colorectal cancer and showing promising activity in ovarian cancer and mesothelioma. Methods Following complete cytoreduction, HIPEC was performed using 460 mg/m² oxaliplatin in 5% dextrose for 30 min at a temperature of 41–42°C. Open perfusion (coliseum technique) was performed in all patients. Metabolic, electrolyte, and hemodynamic changes were recorded during chemoperfusion as well as postoperative morbidity, mortality, late toxicity, and survival. Results From July 2005 to January 2007, 52 patients were treated. Chemoperfusion with 5% dextrose resulted in temporary significant hyperglycemia, hyponatremia, and metabolic acidosis. Major morbidity developed in 24% of patients, while 30-day mortality did not occur. One patient developed unexplained repeated episodes of hemoperitoneum. Chemoperfusion with oxaliplatin resulted in mild hepatic toxicity evidenced by persistent elevation of glutamyl transferase and alkaline phosphatase 1 month after surgery. After a mean follow-up time of 14.5 months, nine patients died from disease progression. In colorectal cancer patients, actuarial overall survival was 80% at 1 year. Conclusion Cytoreduction with HIPEC using high-dose oxaliplatin leads to manageable metabolic and electrolyte disturbances and frequent mild hepatic toxicity without discernible impact on postoperative morbidity. Longer follow-up in a larger patient cohort will be required to assess the real risk of unexplained hemoperitoneum observed in one patient, and to establish the long-term effect on local relapse and survival.     

Hepatic Arterial Infusion of Oxaliplatin and Intravenous LV5FU2 in Unresectable Liver Metastases from Colorectal Cancer after Systemic Chemotherapy Failure

Background We have previously shown promising activity of hepatic arterial infusion (HAI) oxaliplatin combined with intravenous (IV) 5-fluorouracil (5-FU) and leucovorin (LV) as first-line chemotherapy in patients with colorectal liver metastases (CRLM) (intent-to-treat [ITT] objective response rate [ORR], 64%; secondary resection rate, 18%; overall survival [OS], 27 months). Whether this regimen could be beneficial after systemic chemotherapy failure is unknown. Methods Patients with unresectable CRLM and history of systemic chemotherapy failure were treated bimonthly with HAI oxaliplatin (100 mg/m² 2 hours) combined with IV LV and IV bolus and infusional 5FU (modified LV5FU2 regimen). Results Forty-four consecutive patients (median age 56 years; median number of prior systemic chemotherapy regimens, 2 range 1–5) were included, of whom 43 (98%) had previously received oxaliplatin (n = 34), irinotecan (n = 37), or both (n = 28). Patients received a median of nine cycles of HAI oxaliplatin and IV modified LV5FU2 (range 0–25). Toxicity included grade 3–4 neutropenia (43%), grade 2–3 neuropathy (43%), and grade 3–4 abdominal pain (14%). We observed 24 partial ORs (62%) among the 39 assessable patients (ITT ORR, 55%; 95% CI, 40–69%), including 17, 12, and 12 patients who had failed to respond to prior systemic chemotherapy with FOLFIRI, FOLFOX, or both, respectively. Tumor response allowed further R0 surgical resection (n = 7) or radiofrequency ablation (n = 1) of initially unresectable CRLM in eight patients (18%). Median progression-free survival and OS were 7 and 16 months, respectively. Conclusions HAI oxaliplatin and IV LV5FU2 is feasible, safe, and shows promising activity after systemic chemotherapy failure, allowing surgical resection of initially unresectable CRLM in 18% of patients.     

Experimental study of renal disorder caused by oxaliplatin in rat renal cortical slices

Background Oxaliplatin is a newly developed antitumor platinum complex that is known to have low nephrotoxicity. The inhibitory effects of oxaliplatin on several tubular functions were compared with those of cisplatin and carboplatin, using a renal cortical slice system.Methods and results Rat renal cortical slices were incubated with 0.25mM to 2.0mM of oxaliplatin, cisplatin, on carboplatin at 37°C for 120min. Para-amino hippuric acid (PAH) accumulation, gluconeogenesis, and ATP content in the rat renal slices were determined. PAH accumulation was not inhibited by carboplatin, but it was signific-antly inhibited by oxaliplatin and cisplatin. Inhibition of PAH accumulation by cisplatin was greater than that by oxaliplatin. Gluconeogenesis was not decreased by carboplatin, but it was suppressed by oxaliplatin and cisplatin in a dose-dependent manner. The decrease in gluconeogenesis induced by oxaliplatin was significantly greater than that induced by cisplatin. ATP content in the renal slices was decreased by oxaliplatin, cisplatin, and carboplatin to almost the same extent. As an in vivo experiment, 21.6mmole/kg of oxaliplatin, cisplatin, or carboplatin was injected into rats; then blood urea nitrogen (BUN) and serum creatinine were determined on day 4. Significantly elevated levels of BUN and serum creatinine were observed only in the rats injected with cisplatin.Conclusions Oxaliplatin did not cause nephrotoxicity in the in vivo study; however, the nephrotoxic pattern of oxaliplatin observed in the renal cortical-slice system resembled that of cisplatin. The reason why oxaliplatin is less nephrotoxic than cisplatin in vivo could not be fully elucidated in the present experiment using the renal cortical-slice system.     

加味阳和汤防治奥沙利铂周围神经毒性的临床观察

目的观察加味阳和汤防治奥沙利铂神经毒性的临床疗效。方法将60例符合纳入标准的结直肠癌患者随机分为治疗组和对照组,各30例。两组均给予含奥沙利铂的化疗方案进行化疗,治疗组化疗同时加用加味阳和汤,各组均以21 d为1个周期,共治疗4个周期,观察治疗后两组患者神经毒性发生率和程度及血流动力学改变。结果治疗后治疗组神经系统毒性的发生率明显低于对照组,差异有统计学意义(P0.05);治疗后两组血流动力学指标均较治疗前明显改善,差异有统计学意义(P0.05);治疗组三项指标均低于对照组,差异有统计学意义(P0.05)。结论加味阳和汤对奥沙利铂导致的神经系统毒性可有效改善患者血液动力学指标,而且可以预防和降低其周围神经毒性。     

奥沙利铂对结肠癌细胞XIAP表达及凋亡的影响

目的 研究奥沙利铂对人结肠癌细胞株SW1116中XIAP表达及凋亡的影响,探讨其诱导凋亡的作用机制。方法 应用流式细胞仪检测XIAP表达及凋亡的情况。结果 奥沙利铂对XIAP表达有明显的抑制作用（P〈0.05）,凋亡率明显高于对照组（P〈0.01）。结论 奥沙利铂具有抑制结肠癌细胞株SW1116中XIAP表达,诱导结肠癌细胞凋亡作用,其机制与抗凋亡相关基因表达减弱有关。     

多西紫杉醇联合5-氟尿嘧啶、亚叶酸钙及草酸铂治疗胃癌肝转移的临床观察

目的 观察多西紫杉醇联合5-氟尿嘧啶、亚叶酸钙及草酸铂治疗胃癌肝转移的疗效及毒副反应。方法 多西紫杉醇50mg/m^2,d1,草酸铂100mg/m²,d1,5-Fu750mg/（m².d）持续静脉滴注48h,d1～2,CF200mg,d1～3,每2周重复。完成3周期后评价疗效。结果 全组24例患者,治疗后CR2例,PR12例,RR（CR＋PR）为58.3%。中位生存时间（MST）11.2个月,中位疾病进展时间（TTP）6.6个月。主要不良反应为骨髓抑制、神经毒性、粘膜炎等。结论 多西紫杉醇联合5-氟尿嘧啶、亚叶酸钙及草酸铂治疗胃癌肝转移有效率较高,可提高患者的生存质量,毒副作用能耐受。     

生脉注射液联合奥沙利铂抗肿瘤实验研究

目的:观察生脉注射液联合奥沙利铂(Oxalip latin)应用后瘤重抑制率、免疫功能、肝肾功能以及外周血象的变化。方法:建立H22肝癌荷瘤鼠模型后,随机分为5组,对照组、Oxalip latin组、生脉注射液(大、中、小剂量) Oxalip latin组,每组10只。造模次日开始进行干预,对照组、Oxalip latin组、生脉注射液(大、中、小剂量) Oxalip latin组分别予ip等容量5%葡萄糖注射液、Oxalip latin 6 mg/kg、生脉注射液(大14 mL/kg、中7 mL/kg、小3.5 mL/kg剂量) Oxalip latin 6 mg/kg,用药14 d。停药次日处死,观察瘤重抑制率、免疫功能、肝肾功能、外周血细胞变化。结果:(1)生脉注射液联合Ox-alip latin各组肿瘤生长明显低于Oxalip latin组和对照组(均P<0.05);(2)与对照组相比,Oxalip latin组CD3、CD4、CD4/CD8、IgG、ISM值明显降低(P<0.05),而各生脉联合组CD3、CD4、CD4/CD8、IgG、IgM、IgA值明显升高(P<0.05);(3)与对照组相比,Oxalip latin组ALT升高、WBC降低,而各生脉联合组相对于Oxalip latin组ALT降低、WBC升高(P<0.05)。结论:生脉注射液联合奥沙利铂(Oxalip latin)应用抑瘤效果加强、免疫功能提高,毒副反应减少。     

Effect of Jianpi Bushen formula for colon cancer patients who underwent adjuvant chemotherapy: Statistical analysis plan for a multicenter trialOA

Background: Patients with colon cancer who receive chemotherapy usually experience various gastrointestinal adverse reactions, including nausea, vomiting, and diarrhea, which make it challenging for them to adhere to treatment. As an effective traditional Chinese medicine, the Jianpi Bushen formula has been widely used to alleviate the side effects of chemotherapy.Objective: To evaluate the efficacy and safety of Jianpi Bushen formulae for patients who undergo chemotherapy. This statistical anal...     

清肠解毒方对大肠癌术后复发化疗患者肿瘤标记物水平及生活质量的影响

目的:探讨清肠解毒方对大肠癌术后复发化疗患者的生活质量及肿瘤标记物水平的影响。方法:选取出现复发的大肠癌患者60例,随机分为观察组与对照组各30例。两组化疗方案均为奥沙利铂联合卡培他滨或者盐酸伊立替康联合卡培他滨,观察组加用清肠解毒方治疗。比较两组患者治疗前后血清CEA、AFP、CA-125、CA-199水平与ECOG评分变化。结果:两组患者治疗后血清CEA、AFP、CA-125、CA-199水平显著低于治疗前(P<0.05)。此外,治疗后观察组患者的血清CEA和CA-199水平显著低于对照组(P<0.05)。生活质量方面,治疗后两组患者ECOG评分均显著低于治疗前,差异有统计学意义(P<0.05);且观察组患者治疗后ECOG评分显著低于对照组,差异有统计学意义(P<0.05)。结论:清肠解毒方能够明显改善大肠癌术后化疗患者的生活质量,降低血清肿瘤标记物浓度,值得临床应用。     

应用水胶敷料在预防奥沙利铂致静脉炎的效果观察

目的探究水胶敷料对奥沙利铂致静脉炎的预防效果,以降低静脉炎的发生率。 方法对中国医科大学附属第一医院2015年1月至2016年3月76例首次化疗行XELOX方案即静脉输注奥沙利铂和口服卡培他滨片的结肠癌患者,随机分为观察组和对照组,观察组采用水胶敷料在穿刺点上方沿血管走行外敷,对照组常规处理,比较两组静脉炎发生率。 结果观察组静脉炎发生率10.5%,对照组静脉炎发生率31.6%,两组比较差异有统计学意义（χ²=5.067,P<0.05）。 结论水胶敷料可以有效预防奥沙利铂致静脉炎,很好的保护患者的外周静脉,且操作简单,患者感觉舒适,也能减少不必要的人力物力,值得临床推广。