Clinical pharmacokinetics of oxaliplatin in a hemodialysis patient with advanced gastric cancer

We administered FOLFOX (oxaliplatin (L-OHP) plus infusional 5-fluorouracil (5-FU) and leucovorin) to an hemodialysis (HD) patient with advanced gastric cancer (AGC), and investigated pharmacokinetics (PKs) and dialyzability of L-OHP. The patient was a 54-year-old Japanese man with a diagnosis of inoperable AGC. FOLFOX was instituted 3?h prior to the start of a 4?h HD period with the L-OHP and 5-FU doses reduced by 50% for the first cycle, and 30% reduced dose was administered for the second cycle. We performed an analysis of the PKs of L-OHP during these two cycles. Volume of distribution and area under the curve of the 30% reduced L-OHP dose were 56.7?L and 30.0?μg·h/mL, respectively. A dose reduction of L-OHP by 30%?50% may be advisable for the initial administration, given the need for careful administration of chemotherapy in HD patients, with particular attention to the development of hematological toxicities and neuropathy.     

Gemcitabine,paclitaxel, and oxaliplatin (GEMPOX) in the treatment of relapsed/refractory intracranial nongerminomatous germ cell tumors

Intracranial germ cell tumors (GCT) account for less than 5% of all central nervous system tumors in children in Western countries. Approximately 40% are nongerminomatous GCT (NGGCT). Despite correct treatment, 16% to 47% of the patients will relapse. There are no standard approaches in case of recurrence, and treatment in this situation remains a challenge. We report three patients diagnosed with relapsed intracranial NGGCT treated with gemcitabine, paclitaxel, and oxaliplatin, in whom the tumor showed a remarkable response with normalization of tumor markers.     

Hepatic Artery Infusion Chemotherapy Using Fluorouracil,Leucovorin, and Oxaliplatin versus Transarterial Chemoembolization as Initial Treatment for Locally Advanced Hepatocellular Carcinoma: A Propensity Score–Matching Analysis

PurposeTo compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with a modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX) regimen with that of transarterial chemoembolization as a locoregional treatment for patients with locally advanced hepatocellular carcinoma (HCC).MethodsThis retrospective study included adult patients with locally advanced HCC who received first-line treatment with either HAIC-mFOLFOX or conventional transarterial chemoembolization monotherapy from January 2015 to December 2016. The outcomes, including tumor response rates, evaluated via imaging assessment using the modified response evaluation criteria in solid tumors; overall survival; progression-free survival; and safety, were compared. The propensity score–matching methodology was used to reduce the influence of confounding factors on the outcomes.ResultsThe study included 131 patients with locally advanced HCC who underwent transarterial chemoembolization and 101 who received HAIC-mFOLFOX as initial treatment. After propensity score matching (n = 67 in each group), patients who received HAIC-mFOLFOX had a higher objective response rate (43.3% vs 13.4%, P = .001), longer median overall survival (13.9 vs 6.0 months, P < .001), and longer median progression-free survival (6.4 vs 2.8 months, P = .001) than those who underwent transarterial chemoembolization. The survival benefit with HAIC-mFOLFOX was strengthened in patients with HCC with vascular invasion (hazard ratio: 0.379; 95% confidence interval: 0.237–0.607). HAIC-mFOLFOX was associated with lower incidences of severe adverse events (8.9% vs 22.9%) and liver toxicity than transarterial chemoembolization.ConclusionsCompared with transarterial chemoembolization, HAIC-mFOLFOX is a potentially safer and more effective locoregional therapy for patients with locally advanced HCC.     

Efficacy of Traditional Chinese Medicines in Preventing Oxaliplatin-induced Peripheral Neurotoxicity in Cancer Patients: A Network Meta-analysis

Objective Oxaliplatin-induced peripheral neurotoxicity(OIPN) is the main limitation for its continuation in cancer patients.Traditional Chinese medicines(TCMs) have been used to prevent OIPN in China and have been demonstrated to be effective.However,due to the lack of direct comparison among TCMs,it remains unclear that which TCM is the best for OIPN prevention.Consequently,the present study aimed to compare the relative efficacies of TCMs to find out the best TCM by applying a network meta-analysis.Methods Studies were identified by searching PubMed,EMbase,Cochrane Libraries,CNKI,WanFang,and WeiPu database from January 1990 to May2016.Randomized controlled trials(RCTs) that evaluated the efficacy of TCMs in preventing OIPN in cancer patients were included.Statistical analysis was performed with ADDIS 1.1 6.6.Results Twenty-five RCTs(1572 patients) involving five TCMs were included.The results of network meta-analyses showed that compared with oxaliplatin-based chemotherapy alone,the combination with Huangqi Injection(HQI),Shenmai Injection(SMI),Shenfu Injection(SFI),Buyang Huanwu Decoction(BHD),and Huangqi Guizhi Wuwu Decoction(HGWD) could decrease the overall OIPN incidence and the severe OIPN incidence in cancer patients.In addition,probability ranking results showed the order of efficacy in preventing overall OIPN incidence was HQI HGWD SFI =SMI BHD,while the order of efficacy in preventing severe OIPN incidence was HQI HGWD BHD SFI = SMI.Conclusion All five TCMs are effective neuroprotective agents against OIPN.Among these TCMs,HQI and HGWD were superior to others in clinical efficacy.Moreover,Astragalus membranaceus might be a more promising herb for the OIPN prevention.However,more direct head-to-head RCTs with high quality and large sample size are still needed to further confirm the conclusion.     

多肽mPEG-SC20k-HM-3联合奥沙利铂对人肝癌细胞SMMC-7721裸鼠移植瘤的抑制作用

mPEG-SC_20k-HM-3是具有整合素亲和性的一种新型高效血管生成抑制多肽,为探索其与传统化疗药物联用的抗肿瘤活性,建立人肝癌细胞SMMC-7721裸鼠移植瘤模型,选用奥沙利铂为化疗药物,根据临床前抗肿瘤药效学方法评价联合用药的抑瘤作用,并用金氏公式判断两种药物的联合作用。结果显示,与单独用药相比,联合用药组的抑瘤效果更好,且均具有显著差异(P<0.05)。其中,奥沙利铂(7.5 mg/kg)联合mPEG-SC_20k-HM-3(73.4 mg/kg)的肿瘤抑制率为84.6%,抑制作用比单用奥沙利铂(7.5 mg/kg)和单用mPEG-SC_20k-HM-3(73.4 mg/kg)均有显著提高。根据金氏公式计算,其Q值为1.164(>1.15),可判定该组的用药组合表现出协同作用。结果表明,mPEG-SC_20k-HM-3与奥沙利铂单独给药均能抑制肿瘤生长,两者联用对肝细胞癌具有协同作用。     

益气温阳活血法治疗胃癌化疗致神经毒性临床研究

目的:观察益气温阳活血法内外合治对胃癌应用含奥沙利铂方案化疗所致神经毒性的临床疗效。方法 :将应用奥沙利铂后化疗出现神经毒性的64例胃癌患者随机分为观察组(n=34)与对照组(n=30),对照组予甲钴胺片口服,观察组在此基础上加用益气温阳活血中药内外合治。2个月后观察两组患者疼痛缓解情况、临床疗效、症状平均缓解时间及生活质量(KPS)评分变化情况。结果:观察组疼痛缓解情况、临床疗效、治疗起效时间、KPS评分情况明显优于对照组,两组比较差异有统计学意义(P0.01或P0.05)。结论 :益气温阳活血法内外合治能有效治疗奥沙利铂化疗所致周围神经毒性。     

Genetic determinants of chronic oxaliplatin‐induced peripheral neurotoxicity: a genome‐wide study replication and meta‐analysis

We aimed at validating the role of genetic variants identified by a recent genome‐wide association study (GWAS) as determinants of chronic oxaliplatin‐induced peripheral neurotoxicity (OXAIPN). Eight polymorphisms (rs10486003, rs2338, rs843748, rs797519, rs4936453, rs12023000, rs17140129, and rs6924717) were genotyped in a total of 150 colorectal cancer patients of Caucasian origin receiving oxaliplatin‐based chemotherapy. The severity grade of chronic OXAIPN was assessed by NCI‐CTC criteria and the clinical version of the Total Neuropathy Score^© (TNSc^©). None of the polymorphisms investigated was found associated with grade ≥ 2 chronic OXAIPN (NCI‐CTC criteria), while a nominal association emerged for ACYP2 rs843748 when using the TNSc^© scale (dominant model: odds ratio [OR]: 0.27, 95% confidence interval [CI]: 0.10–0.75, P = 0.008). In the combined analysis of this results with data of the two previously published studies which assessed chronic OXAIPN by NCI‐CTC criteria, evidence suggestive of association with chronic OXAIPN (NCI‐CTC criteria) was found for ACYP2 rs843748 (dominant model: OR: 2.40, 95%CI: 1.40–5.24, P = 0.027), which, however, did not remain significant after correction for multiple testing (threshold P‐value <0.00625). These findings suggest a minor role of the single nucleotide polymorphisms (SNPs) investigated as genetic determinants of chronic OXAIPN. These results also highlight the importance of replication studies with meta‐analysis for validation of GWAS findings.     

多西他赛联合奥沙利铂和替吉奥与DCF方案一线治疗晚期胃癌的对比研究

目的观察和比较多西他赛联合奥沙利铂和替吉奥与DCF方案一线治疗晚期胃癌的疗效及毒副作用。方法收集2009-08-01—2011-06-15深圳市人民医院符合入组条件的60例晚期胃癌患者,采用随机数字表法分为2组。DSOX组30例:多西他赛75mg/m2,持续静脉滴入1h,d1;奥沙利铂130mg/m2,持续静脉滴入3h,d1;替吉奥40mg/m2,口服,2次/d,d1~d14。DCF组30例:多西他赛75mg/m2,持续静脉滴入1h,d1;顺铂75mg/m2,静脉滴入,d1;氟尿嘧啶500mg/m2,静脉滴入,d1~d5。每例患者至少完成2个周期化疗。对疗效及不良反应进行对比观察。结果 DSOX和DCF组的近期有效(CR+PR)率分别为53.3%(16/30)和46.7%(14/30),差异无统计学意义,z=-0.427,P=0.669。中位疾病进展时间分别为7.0和6.8个月,差异无统计学意义,χ2=0.413,P=0.520。中位生存期分别为12.0和11.7个月,差异无统计学意义,χ2=0.048,P=0.826。2组的主要不良反应为骨髓抑制、脱发、神经毒性和胃肠道反应,不良反应发生率差异无统计学意义,P>0.05。DSOX组的骨髓抑制与胃肠道反应相对更轻。结论多西他赛联合奥沙利铂和替吉奥一线治疗晚期胃癌的疗效较好,不良反应可以耐受,值得临床进一步研究应用。     

Palliative chemotherapy for patients 70 years of age and older with metastatic colorectal cancer: a single-centre experience

BackgroundMetastatic colorectal cancer (mcrc) commonly affects elderly people, an understudied subset of patients. We analyzed the survival impact of the first and subsequent lines of chemotherapy in eligible non-trial patients 70 years of age and older with mcrc treated between 2004 and 2012.MethodsThis single-centre retrospective analysis estimated overall survival (os) and progression-free survival (pfs) using the Kaplan–Meier method. Multivariate analysis was used to adjust for age, sex, Eastern Cooperative Oncology Group performance status, score on the Charlson comorbidity index, dependency in activities of daily living, and exposure to 1 or more chemotherapy doublets, capecitabine alone, or best supportive care (bsc).ResultsOf 109 patients identified, 29 elected bsc, and 80 received chemotherapy. In multivariate analysis, age was not associated with os [hazard ratio (hr): 0.99; 95% confidence interval (ci): 0.92 to 1.05], but a performance status of 2 or higher was associated with a decreased likelihood of survival (hr: 3.12; 95% ci: 1.87 to 5.76), and exposure to 1 or more doublets was associated with improved survival (hr: 0.33; 95% ci: 0.17 to 0.66). In univariate analysis, a trend toward improved os was observed for first-line doublet chemotherapy compared with capecitabine (hr: 0.66; 95% ci: 0.41 to 1.07), and pfs was superior (hr: 0.46; 95% ci: 0.26 to 0.84). Compared with exposure to 1 doublet, exposure to the 3 potential cytotoxic chemotherapies was not associated with improved os (hr: 0.77; 95% ci: 0.41 to 1.43). The incidence of neutropenia with first-line folfiri was 40%; the incidences of bevacizumab-related arterial and venous thrombosis were both 8%.ConclusionsExposure to 1 or more doublet chemotherapies for mcrc was associated with better outcomes in non-trial patients 70 years of age and older. Elderly patients treated with palliative chemotherapy and bevacizumab should be monitored carefully for arterial and venous thrombotic events.