Subacute reversible toxic encephalopathy related to treatment with capecitabine: A case report with literature review and discussion of pathophysiology

IntroductionCapecitabine, a 5-fluorouracil (5FU) pro-drug, is increasingly used in breast and gastrointestinal cancers due to its more convenient oral route of administration when compared to 5FU. Despite its widespread use, there are only a few reports on capecitabine CNS toxicity, while the pathogenic basis of such toxicity remains unclear.CaseA 69-year-old male presented with recurrent generalized seizures 2.5 months after preoperative chemoradiotherapy with capecitabine in locally advanced rectal cancer. Brain MRI revealed a diffuse, subcortical white matter alteration suggestive of vasogenic edema. The diagnosis of toxic encephalopathy was supported after elimination of alternative causes of the neurological dysfunction and complete resolution of clinical and imaging findings after 3 months of no further chemotherapy.ConclusionsGiven the expanding use of capecitabine, physicians should be aware of this potential complication when a neurological worsening occurs during or after treatment with this chemotherapeutic agent. In our case, as in previously described cases encephalopathy was characterized by a favorable course after cessation of the drug. Vasogenic edema rather than cytotoxic edema may play a pivotal pathogenetic role in this form of encephalopathy.     

Role of Plasmapheresis in the Management of Acute Kidney Injury in Patients With Multiple Myeloma: Should We Abandon It?

The aim of the current study was to determine whether plasmapheresis in combination with chemotherapy could significantly remove free light chains (FLC) in multiple myeloma (MM) patients with acute kidney injury (AKI) and therefore improve renal recovery and patient survival. During the study period, 29 patients with MM and AKI presented to our unit and were treated with two different therapy modalities (plasmapheresis with chemotherapy or bortezomib). At the end of treatment, a significant decrease of FLCs was present in the group treated with plasmapheresis compared to the bortezomib group. Patients treated with plasmapheresis had similar survival compared to patients treated with bortezomib. There was a significantly higher decrease of FLCs and longer survival in patients treated with three or more plasmapheresis sessions than in patients treated with two plasmapheresis sessions. Plasmapheresis therapy still remains a useful and effective method in the treatment of AKI in MM patients. Plasmapheresis significantly reduces FLCs compared to bortezomib especially with higher number of plasma exchange sessions but it must be combined with other chemotherapy agents in order to prolong renal recovery and therefore patient survival.     

Long-Term Follow-Up of R-CHOP With Bevacizumab as Initial Therapy for Mantle Cell Lymphoma: Clinical and Correlative Results

BackgroundEmerging evidence indicates that MCL has increased angiogenesis within the tumor microenvironment. We initiated a phase II trial to determine if the addition of bevacizumab to the standard R-CHOP regimen could enhance antitumor effects in patients with previously untreated MCL.Patients and MethodsEleven patients with previously untreated MCL received bevacizumab at 15 mg/kg on day 1, and standard CHOP-21 (CHOP given every 21 days per cycle) with rituximab (375 mg/m² per cycle) on day 3 of each cycle for a total of 6 cycles. Planned study end points included safety and efficacy assessment, and exploratory analysis of angiogenic profiles. The study was suspended in August of 2010 based on safety findings in DLBCL (diffuse large B-cell lymphoma) of increased cardiovascular events with the regimen.ResultsBeyond the standard R-CHOP safety profile, Grade 3 left ventricular dysfunction developed in 2 patients (18%), Grade 1/2 hypertension, proteinuria, and bleeding each developed in 1 patient (9%). The overall response rate was 82% with 36% complete response (CR)/complete response unconfirmed (CRu). The median progression-free survival (n = 11) was 18 months (95% confidence interval, 3-not reached), and 3-year overall survival rate was 82%. Correlative studies showed increased vascular endothelial growth factor receptor 1 expression in tumor cells at baseline, and elevated levels of plasma vascular endothelial growth factor (VEGF) throughout treatment.ConclusionThe addition of bevacizumab to the standard R-CHOP regimen did not appear to significantly improve efficacy beyond that observed from previous studies using R-CHOP alone. Therapeutic strategies that provide sustained inhibition on VEGF-related and VEGF-independent targets within the tumor microenvironment might further improve antiangiogenic effects and warrant further exploration in MCL.     

Factors Influencing the Use of Antitumoral Chemotherapy in the South East of England

Abstract

Influences on the use of chemotherapy for the treatment of cancer within the South East region of England for patients diagnosed with colorectal, lung, breast and prostate cancer were investigated. The variables investigated as possibly influencing the selection of chemotherapy were the sex of the patients, their age, the year of diagnosis, the cancer site, the cancer stage, the index of multiple deprivation (IMD) and the cancer network of residence. Logistic regression used to adjust the proportion receiving chemotherapy in relation to other variables considered showed significant differences in the proportion of patients receiving chemotherapy between different cancer sites and different networks. There was also a highly significant trend seen in use of chemotherapy over time; the adjusted proportion of patients receiving chemotherapy increasing from 10.6% in 1993 to 24.3% in 2002. Age, stage and cancer site seemed to have the most influence on the use of chemotherapy.     

Inhibition of protein kinases by anticancer DNA intercalator, 4-butylaminopyrimido[4′,5′:4,5]thieno(2,3-b)quinoline

Targeting protein kinases (PKs) has been a promising strategy in treating cancer, as PKs are key regulators of cell survival and proliferation. Here in this study, we studied the ability of pyrimido[4′,5′:4,5]thieno(2,3-b)quinolines (PTQ) to inhibit different PKs by performing computational docking and in vitro screening. Docking studies revealed that 4-butylaminopyrimido[4′,5′:4,5]thieno(2,3-b)quinoline (BPTQ) has a higher order of interaction with the kinase receptors than other PTQ derivatives. In vitro screening confirms that BPTQ inhibits VEGFR1 and CHK2, with the IC₅₀ values of 0.54 and 1.70 µmol/L, respectively. Further, cytotoxicity of BPTQ was measured by trypan blue assay. Treatment with BPTQ decreased the proliferation of HL-60 cells with an IC₅₀ value of 12 µmol/L and induces apoptosis, as explicated by the fall in the mitochondrial membrane potential, annexin V labeling and increased expression of caspase-3. Taken together, these data suggest that BPTQ possess ability to inhibit PKs and to induce cell death in human promyelocytic leukemia cells.     

膀胱癌术后羟喜树碱灌注化疗的护理体会

目的总结膀胱癌术后膀胱内灌注化疗的护理特点。方法对我科52倒经尿道膀胱肿瘤电切术后一周，膀胱部分切除术后2周的浅表性膀胱癌患者用羟喜树碱45mg加生理盐水20ml进行膀胱内灌注，在灌注的各个环节做好护理工作。结果有5例出现尿频、尿急、尿痛，2例出现血尿，1例出现脱发，经处理后（停药1周后）症状消失，2例白细胞降低，经服药后5d症状消失，4例食欲减退、乏力，经平衡膳食后饮食正常。随访一年，有5例复发。结论灌注前做好心理护理和排空膀胱护理，灌注后做好并发症的观察、护理，是该治疗的重要措施。