Asparaginase in Acute Lymphoblastic Leukemia

Cure rates in pediatric acute lymphoblastic leukemia have significantly improved over the past decades. Now, almost 90% of children will survive the disease. The cure rates in adolescents, young adults, and adults have not kept pace with the improvements in younger patients, even though almost an equal proportion of adult patients achieve complete remission as their pediatric counterparts. Differences in treatment regimens might be important. Intensive use of asparaginase has been a key component of successful pediatric therapy. In this review, we focus on the use of asparaginase and the potential of optimizing asparaginase use via monitoring to minimize adverse drug events and improve efficacy of the drug.     

Effect of omeprazole on the pharmacokinetics and toxicities of irinotecan in cancer patients: a prospective cross-over drug-drug interaction study

Background

Omeprazole is one of the most prescribed medications worldwide and within the class of proton pump inhibitors, it is most frequently associated with drug interactions. In vitro studies have shown that omeprazole can alter the function of metabolic enzymes and transporters that are involved in the metabolism of irinotecan, such as uridine diphosphate glucuronosyltransferase subfamily 1A1 (UGT1A1), cytochrome P-450 enzymes subfamily 3A (CYP3A) and ATP-binding cassette drug-transporter G2 (ABCG2). In this open-label cross-over study we investigated the effects of omeprazole on the pharmacokinetics and toxicities of irinotecan.

Methods

Fourteen patients were treated with single agent irinotecan (600 mg i.v., 90 min) followed 3 weeks later by a second cycle with concurrent use of omeprazole 40 mg once daily, which was started 2 weeks prior to the second cycle. Plasma samples were obtained up to 55 h after infusion and analysed for irinotecan and its metabolites 7-ethyl-10-hydroxycampothecin (SN-38), SN-38-glucuronide (SN-38G), 7-ethyl-10-[4-(1-piperidino)-1-amino]-carbonyloxycamptothecin (NPC) and 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin (APC) by high-performance liquid chromatography (HPLC). Non-compartmental modelling was performed. Toxicities were monitored during both cycles. Paired statistical tests were performed with SPSS.

Results

The exposure to irinotecan and its metabolites was not significantly different between both cycles. Neither were there significant differences in the absolute nadir and percentage decrease of WBC and ANC, nor on the incidence and severity of neutropenia, febrile neutropenia, diarrhoea, nausea and vomiting when irinotecan was combined with omeprazole.

Conclusion

Omeprazole 40 mg did not alter the pharmacokinetics and toxicities of irinotecan. This widely used drug can, therefore, be safely administered during a 3-weekly single agent irinotecan schedule.     

替吉奥联合奥沙利铂与替吉奥联合多西他赛治疗晚期胃癌的临床观察

目的观察国产替吉奥联合奥沙利铂与替吉奥联合多西他赛方案治疗晚期胃癌的近期疗效和毒副反应。方法43例晚期胃癌患者,替吉奥联合奥沙利铂组（OXA组）26例,具体为：替吉奥胶囊：40mg／m2,口服,2次／d,第1～14天,3w为1周期;OXA：130mg／m2,静滴,第1天,3w为1周期。替吉奥联合多西他赛组（TXT组）17例,具体为：替吉奥胶囊用法同OXA组;TxT：60mg／m2,静滴,第1天,3w为1周期。治疗2周期后评价近期疗效、毒副反应和生活质量。结果43例患者均可评估毒副反应,42例患者可评价近期疗效,OXA组与TXT组有效率分别为57．7％和31．3％,差异无统计学意义（P=0．096）。TXT组自细胞减少（94．1％）、口腔炎（35．3％）和便秘（76．5％）的总发生率明显高于OXA组（73．1％、3．8％、38．5％）,差异有统计学意义（P=0．019,0．006,0．015）;OXA组的神经毒性发生率（53．8％）显著高于TXT组（17．6％）,差异有统计学意义（P〈0．05）。结论替吉奥联合奥沙利铂治疗晚期胃癌与替吉奥联合多西他赛相比,疗效相当,毒副反应TXT组略高于OXA组。     

含米托蒽醌化疗方案治疗血液恶性肿瘤的毒副作用临床观察

本文应用含米托蒽醌的化疗方案治疗37例血液恶性肿瘤，观察其毒副作用。结果表明，含米托蒽醌的方案毒副作用有骨髓抑制、胃肠道反应、心肝肾脏器损害、发热等。这些毒副作用症状大多轻微，且易耐受。最为严重的副作用是骨髓抑制，4例死于骨髓抑制后的出血和感染。作者认为，定期复查骨髓象、外周血象和心电图等，加强预防性措施，则可避免其毒性所造成的严重后果，提高血液系统恶性肿瘤的缓解率。     

Radiothérapie conformationnelle avec modulation d’intensité dans les carcinomes bronchiques non à petites cellules

Intensity modulated radiotherapy is increasingly used in non-small-cell lung cancers despite a low level of evidence. A literature review was conducted. Several critical physical and dosimetric uncertainties are however unsolved. Methods to circumvent these limitations are being developed. In several retrospective studies, survival rates were at least similar with intensity-modulated radiotherapy as those reported with three-dimensional irradiation. To date, intensity modulated radiotherapy might be authorized in complex anatomical situations such as tumours close to the spinal cord (such as Pancoast Tobias, paraspinal and paracardiac tumours) or with limited motion amplitudes. Dosimetric benefits should also account for 4D dose distribution issues. The reduction of intermediate and high doses in the organs at risk with intensity modulated radiotherapy is advantageous. However, the effect of low doses in large volumes (lung, bone, unspecified tissues along beam paths) and the effect of increasing integral dose are still poorly known. In conclusion, dose–volume correlations need to be better documented and prospective randomized trials should be encouraged.     

TP、PTP及CAP化疗方案治疗上皮性卵巢癌的比较

目的探讨进口紫杉醇(泰素)与铂类联合化疗方案(TP)、国产紫杉醇(紫素)与铂类联合化疗方案(PIP)治疗上皮性卵巢癌的疗效及毒性,并与环磷酰氨、阿霉素及铂类方案(CAP)进行比较。方法对1993年12月至1999年4月采用TP、PIP及CAP化疗方案治疗的卵巢癌患者进行回顾性分析。泰素组(TP组)22例、紫素组(PTP组)18例,CAP组38例。结果泰素组有效率为55.6％,紫素组有效率为71.4％;紫杉醇作为一线用药有效率为88.9％,CAP作为一线用药有效率为55.9％。紫杉醇的毒副作用有造血功能抑制、消化道症状、脱发、外周神经炎、肌肉、关节疼痛,其中2例出现Ⅲ度外周神经损伤。结论TP或PTP作为一线用药疗效高于CAP,国产及进口紫杉醇在疗效及副作用上无明显差异。     

Protontherapy of head and neck paragangliomas: A monocentric study

Purpose

The aim of this study was to assess efficacy and safety of proton beam therapy of paragangliomas of the head and neck, rare benign tumours developed close to crucial structures such as cranial nerves and vascular tissues.

宫颈癌术后盆腔复发患者放射治疗效果及预后的影响因素

目的 分析宫颈癌术后盆腔复发患者放射治疗的疗效及不良反应。方法 回顾性分析2004年8月至2016年12月河北医科大学第四医院收治的宫颈癌手术治疗后盆腔复发的患者147例，所有患者均行放射治疗伴或不伴化疗。根据不同的临床因素和病理因素进行分组，logistic回归分析宫颈癌术后盆腔复发患者放疗效果的相关影响因素，采用Kaplan-Meier法统计生存率，并绘制相应生存曲线，生存率及预后相关因素对比使用Log-rank法。采用COX比例风险回归模型进行多因素分析。治疗后不良反应分析采用卡方检验。结果 中位随访时间为33.2个月，95%的患者完成剂量≥ 67 Gy（放疗剂量中位数）的放射治疗，完全缓解（CR）91例（61.9%）。患者5年局部控制率（LC）、无进展生存率（PFS）、无远处转移生存率（DMFS）和总生存率（OS）分别为63.6%、56.0%、73.9%和55.0%。单因素logistic回归分析显示，国际妇产科联盟（FIGO）分期（0~I_B期与Ⅱ_A~Ⅱ_B期）、盆腔侧壁是否受累、复发肿瘤体积为宫颈癌术后盆腔复发患者治疗后完全缓解的相关因素（P<0.05）；多因素统计分析发现，FIGO分期、盆腔侧壁是否受侵是影响宫颈癌术后盆腔复发患者治疗效果和生存的独立因素（P<0.05）；宫颈癌术后盆腔复发盆壁受侵患者出现≥ 2级放射性直肠炎的发生率高于盆壁未受侵者，分别为26.9%和16.7%。结论 本研究表明宫颈癌术后盆腔复发患者经放疗后不良反应可耐受，且盆壁受侵患者不良反应发生率明显高于盆壁未受侵者；术前分期、盆壁是否受侵是影响宫颈癌术后盆腔复发患者放疗效果及远期预后的独立影响因素。     

顺铂与卡铂为主的联合化疗疗效及毒副反应的比较研究

作者近十年间行金属铂诱导化疗84例,其中顺铂 平阳霉素 长春新碱(PVP)组53例;卡铂 平阳霉素 长春新碱(CVP)组31例。治疗结果:PVP和CVP方案的近期疗效相接近,总有效率分别是86.79％和77.41％,两组差异无显著意义。毒副反应的比较表明:PVP以肾毒性、胃肠毒性和耳毒性为主,发生率分别为13.2％、79.24％和11.32％;而CVP则以骨髓毒性和肝毒性为特征,分别为38.70％和12.90％。两组分别出现的毒副反应及其并发症尚未影响诱导化疗的使用。