Bevacizumab and irinotecan treatment for progressive diffuse brainstem glioma: case report

Diffuse brainstem glioma carries a dismal prognosis. The current cornerstone of treatment is radiation therapy. Chemotherapy appears to be ineffective and the role of this treatment in the recurrent or progressive setting is not known. Bevacizumab and irinotecan have been reported to have shown radiographic response and improvement in progression-free survival among patients with malignant supratentorial gliomas. In this paper, we report our experience in an adult patient with progressive diffuse brainstem glioma treated with bevacizumab and irinotecan.     

营养风险与伊立替康导致延迟性腹泻的关系

目的探讨营养风险与伊立替康导致延迟性腹泻的关系。方法对302例次伊立替康化疗的胃肠癌患者采用NRS2002（Nutritional risk screening 2002）评分筛查,分为存在营养风险组与无营养风险组,比较两组患者Ⅱ～Ⅳ度延迟性腹泻及Ⅲ～Ⅳ度以上腹泻的发生率。结果 NRS2002评分筛查存在营养风险组发生Ⅱ～Ⅳ度延迟性腹泻及Ⅲ～Ⅳ度以上腹泻的概率明显大于无营养风险组（P〈0.05）。结论存在营养风险的患者应用伊立替康化疗发生延迟性腹泻的风险较大。     

Sensitivity to previous irinotecan treatment does not predict the efficacy of combination chemotherapy with cetuximab plus irinotecan for wild-type KRAS metastatic colorectal cancer

The aim of this study was to evaluate the association of sensitivity to previous irinotecan-based chemotherapy with efficacy of cetuximab plus irinotecan therapy in metastatic colorectal cancer (MCRC) patients with wild-type KRAS. We analysed a pooled data set consisting of data from 87 MCRC patients from two previous phase II studies (n = 60) and a group given off-protocol treatment (n = 27) following irinotecan-, oxaliplatin-, and fluoropyrimidine-based chemotherapy. Overall objective response rate to cetuximab plus irinotecan was 28.7%, median progression-free survival (PFS) was 5.3 months, and median overall survival was 12.2 months. Objective response rate did not significantly differ between patients with a favourable response to previous irinotecan (n = 23), stable disease (n = 38), or progressive disease (n = 26), with observed rates of 29.2%, 31.6%, and 23.1%, respectively. Additionally, the non-parametric Spearman rank correlation coefficients (ρ) between the PFS of previous irinotecan-based chemotherapy and that of cetuximab plus irinotecan were quite low (ρ = 0.067 and 0.057 in patients with previous irinotecan as first- and second-line therapies, respectively). Although exploratory nature and small sample size may be limitations of this study, these findings indicate that the efficacy of irinotecan plus cetuximab in MCRC patients with wild-type KRAS did not differ by previous sensitivity to irinotecan.     

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.     

Cisplatin and irinotecan combination chemotherapy for advanced thymic carcinoma: evaluation of efficacy and toxicity

Background

Thymic carcinoma is a rare, malignant mediastinal tumor that is definitively distinguished from thymoma by its wide extensiveness and poor prognosis. At present, cisplatin-based triplet or quartet chemotherapy with the second generation antitumor agents, referred to as Einhorn's protocol for germ cell tumors, is used as first-line chemotherapy for advanced thymic carcinoma, though an optimal chemotherapeutic regimen has not yet been established. In this retrospective study, the effectiveness and toxicity of cisplatin and irinotecan combination chemotherapy were evaluated over a nine-year period.

Patients and methods

Patients with advanced thymic carcinoma who were treated with cisplatin and irinotecan combination chemotherapy between January 1, 2002 and December 31, 2010, were retrospectively identified from our database and medical records. The endpoints in this study were disease control, response rate, progression-free survival (PFS), and overall survival (OS). Significant hematological and non-hematological toxicities were also assessed.

Results

Among identified nine patients, disease control was achieved in 8 patients (88.9%), and a clinical response was achieved in 5 (55.6%). The median PFS was 7.9 months, and the median OS was 33.8 months. One- and two-year OS were 77.7% and 55.6%, respectively. Grade 3/4 hematological toxicities were observed in 2 patients (22.2%), and Grade 3/4 non-hematological toxicities were seen in 2 patients (22.2%). No febrile neutropenia or toxic death was recorded.

Conclusion

Cisplatin and irinotecan combination chemotherapy appears to be acceptable for advanced thymic carcinoma as first-line chemotherapy with respect to efficacy, toxicity, and usage in the clinical setting.     

伊立替康加顺铂同步放化疗对局部晚期食管癌的疗效观察

目的探讨伊立替康加顺铂同步放化疗对局部晚期食管癌的疗效及不良反应。方法全部病例化疗均采用顺铂30 mg/m2,伊立替康65 mg/m2,第1天及第8天,21天重复,共4个周期。化疗同时行放疗,标准为1.8～2.0Gy/次,每周5次,直到肿瘤量达50.4～61.2 Gy。结果随访中位时间为24.5个月（2.7～60.3个月）,15例存活2,7例死亡。2年总生存率为42%。31例复发：24例为原位复发5,例为远处转移2,例为局部和远处转移。2年无病生存率为9.2%。3级以上白细胞下降及放射性食管炎发生例数分别为12和6例。结论顺铂加伊立替康同步放疗对局部晚期食管癌患者的疗效较好,毒性小,患者可以耐受。     

抗肿瘤药伊立替康的临床使用研究

目的:研究分析抗肿瘤药伊立替康应用于临床治疗小细胞癌的效果。方法:选择40例小细胞癌患者,随机分为观察组与对照组,每组20例。观察组患者采用伊立替康联合顺铂治疗,对照组采用依托泊苷治疗,观察比较两组患者的治疗有效率及其不良反应情况。结果:观察组的治疗有效率显著高于对照组的治疗有效率(P<0.05);观察组的不良反应发生率小于对照组的不良反应发生率,差异有统计学意义(P<0.05)。结论:临床使用抗肿瘤药伊立替康联合顺铂治疗小细胞癌的疗效显著,且不良反应少,值得临床推广和应用。