19 F MRSI of capecitabine in the liver at 7 T using broadband transmit–receive antennas and dual‐band RF pulses

Capecitabine (Cap) is an often prescribed chemotherapeutic agent, successfully used to cure some patients from cancer or reduce tumor burden for palliative care. However, the efficacy of the drug is limited, it is not known in advance who will respond to the drug and it can come with severe toxicity. ¹⁹ F Magnetic Resonance Spectroscopy (MRS) and Magnetic Resonance Spectroscopic Imaging (MRSI) have been used to non‐invasively study Cap metabolism in vivo to find a marker for personalized treatment. In vivo detection, however, is hampered by low concentrations and the use of radiofrequency (RF) surface coils limiting spatial coverage. In this work, the use of a 7T MR system with radiative multi‐channel transmit–receive antennas was investigated with the aim of maximizing the sensitivity and spatial coverage of ¹⁹ F detection protocols. The antennas were broadband optimized to facilitate both the ¹H (298 MHz) and ¹⁹ F (280 MHz) frequencies for accurate shimming, imaging and signal combination. B₁⁺ simulations, phantom and noise measurements showed that more than 90% of the theoretical maximum sensitivity could be obtained when using B₁⁺ and B₁^? information provided at the ¹H frequency for the optimization of B₁⁺ and B₁^? at the ¹⁹ F frequency. Furthermore, to overcome the limits in maximum available RF power, whilst ensuring simultaneous excitation of all detectable conversion products of Cap, a dual‐band RF pulse was designed and evaluated. Finally, ¹⁹ F MRS(I) measurements were performed to detect ¹⁹ F metabolites in vitro and in vivo. In two patients, at 10 h (patient 1) and 1 h (patient 2) after Cap intake, ¹⁹ F metabolites were detected in the liver and the surrounding organs, illustrating the potential of the set‐up for in vivo detection of metabolic rates and drug distribution in the body. Copyright © 2015 John Wiley & Sons, Ltd.     

Lapatinib nano-delivery systems: a promising future for breast cancer treatment

Introduction: Breast cancer stands the second prominent cause of death among women. For its efficient treatment, Lapatinib (LAPA) was developed as a selective tyrosine kinase inhibitor of receptors, overexpressed by breast cancer cells. Various explored delivery strategies for LAPA indicated its controlled release with enhanced aqueous solubility, improved bioavailability, decreased plasma protein binding, reduced dose and toxicity to the other organs with maximized clinical efficacy, compared to its marketed tablet formulation.

Areas covered: This comprehensive review deals with the survey, performed through different electronic databases, regarding various challenges and their solutions attained by fabricating delivery systems like nanoparticles, micelle, nanocapsules, nanochannels, and liposomes. It also covers the synthesis of novel LAPA-conjugates for diagnostic purpose.

Expert opinion: Unfortunately, clinical use of LAPA is restricted because of its extensive albumin binding capacity, poor oral bioavailability, and poor aqueous solubility. LAPA is marketed as the oral tablet only. Therefore, it becomes imperative to formulate alternate efficient multiparticulate or nano-delivery systems for administration through non-oral routes, for active/passive targeting, and to scale-up by pharmaceutical scientists followed by their clinical trials by clinical experts. LAPA combinations with capecitabine and letrozole should also be tried for breast cancer treatment.     

单药卡培他滨治疗蒽环类药物化疗后复发转移性乳腺癌的临床观察

目的观察单药卡培他滨对蒽环类药物化疗后复发转移性乳腺癌的作用。方法23例复发转移性乳腺癌患者，均经过蒽环类药物治疗后出现疾病进展，给予单药卡培他滨2000mg／（m^2·d），分两次口服，连服2周，3周为1个周期。至少2个周期后评价疗效。结果本组化疗均数为4个周期。CR0例，PR6例，SD13例，PD4例，有效率26．1％，疾病控制率（CR＋PR＋SD）为82．6％（19／23），常见不良反应为手足综合征（65．2％）、皮肤色素沉着（52．7％）、恶心呕吐（43．5％）、腹泻34．8％，1例出现3～4级严重腹泻而住院治疗。结论单药卡培他滨对蒽环类药物化疗后复发转移性乳腺癌仍有一定的疗效，耐受性好。     

Topical Silymarin Administration for Prevention of Capecitabine‐Induced Hand–Foot Syndrome: A Randomized,Double‐Blinded,Placebo‐Controlled Clinical Trial

Hand–foot syndrome (HFS) is a frequent dose‐limiting adverse reaction of capecitabine in patient with gastrointestinal cancers. Silymarin is a polyphenolic flavonoid extracted from the Silybum marianum that exhibits strong antioxidant and antiinflammatory activities. In this study, we evaluated silymarin efficacy in prevention of capecitabine‐induced HFS in patients with gastrointestinal cancers, as the first human study. During this pilot, randomized, double‐blinded, placebo‐controlled clinical trial, the effect of silymarin gel 1%, which is applied on the palms and soles twice daily starting at the first day of chemotherapy for 9 weeks, on HFS occurrence was assessed. Forty patients fulfilled the inclusion criteria assigned to the silymarin or placebo group. World Health Organization HFS grading scale scores were recorded at baseline and every 3 weeks during these 9 weeks. The median WHO HFS scores were significantly lower in silymarin group at the end of the 9^th week (p < 0.05). The scores increased significantly in both placebo and silymarin groups during chemotherapy, but there was a delay for HFS development and progression in silymarin group. Prophylactic administration of silymarin topical formulation could significantly reduce the severity of capecitabine‐induced HFS and delays its occurrence in patients with gastrointestinal cancer after 9 weeks of application. Copyright © 2017 John Wiley & Sons, Ltd.     

优替德隆联合卡培他滨二线治疗转移性乳腺癌的药物经济学评价

目的 从中国卫生体系角度评价优替德隆联合卡培他滨与单用卡培他滨相比二线治疗转移性乳腺癌的经济性。方法 利用临床试验数据和相关文献数据建立分区生存模型,模型的循环周期设为3周,模拟时限为15年,成本和效用数据均采用5%的贴现率进行贴现处理,模型产出指标为增量成本-效果比(incremental cost-effectiveness ratio,ICER),意愿支付阈值(willingness-to-pay,WTP)设为2021年中国1~3倍人均国内生产总值(gross domestic product,GDP)(80 976元/QALY~ 242 928元/QALY)。进行单因素敏感性分析和概率敏感性分析以评价模型参数变化时模型结果的稳定性。结果 基础分析结果显示,优替德隆联合卡培他滨属于高成本高健康获益方案,2个方案相比的ICER值为393 949.83元/QALY。单因素敏感性分析表明优替德隆的价格是对ICER值影响最大的因素,概率敏感性分析表明模型结果具有稳健性。结论 优替德隆联合卡培他滨与单用卡培他滨相比二线治疗转移性乳腺癌不具有经济学优势,但在人均GDP超过131 316元的地区,优替德隆联合卡培他滨成为具有成本-效果优势的方案。     

The Effects of Phyllanthus niruri Linn on Infiltrating Dendritic Cell and Ratio of Neutrophile/Lymphocytes in Chemotherapy of Sprague-Dawley Rats with Colorectal Cancer

Background: Chemotherapy as part of colorectal cancer management can cause death to immunologically active tumor cell, but also it has immune suppressive effect. Phyllanthus niruri Linn is known to has immunomodulatory effect. This study was intended to prove P. niruri Linn effect on infiltrating dendritic cells and Neutrophil/lymphocyte ratios (NLRs) in Sprague–Dawley rats with colorectal cancer which were given capecitabine chemotherapy. Methods: The study was randomized post–test only control group design. The samples were 39 Sprague–Dawley male rats, with body weight around 170–220 grams, induced by 1,2-dimetylhydrazine (DMH) 30 mg/kgBW once per week subcutaneously. On 9th,11th and 13th week, there were four induced rats sacrificed each week to detect colorectal cancer (CRC) development. On the 13th week, all of the 4 sacrificed rats developed colon cancer, so the induction had to be stopped. The rest of 27 induced rats were randomly divided into three groups: control-group (K) were left untreated (9 rats), group P1 (9 rats) were given Capecitabine and group P2 (9 rats) were given Capecitabine with combination of P. niruri Linn extract 13.5 mg/kgBW orally. After 17th week, all rats were terminated and tumor lesion of colon were processed to be paraffin blocks and were stained with HE for evaluating the NLRs, and immunohistochemistry (S100) for evaluating infiltrating dendritic cells. Data was analyzed by using Oneway-Anova-test and post-Hoc LSD-test. Considered significant if p was <0.05. Results: The mean±standard deviation of infiltrating dendritic cells showed increasing value in group P2 (62.11±31.35) compared to group P1 (52.78±29.24) though not statistically significant. The mean of NLRs also showed statistically significant elevation of value in group P2 (0.13±0.05) compared to group P1 (0.04±0.01). Conclusion: Extract of Phyllanthus niruri Linn increasing immunologic status through elevation of infiltrating dendritic cells and NLRs in animal model colorectal cancer with Capecitabine chemotherapy.     

复方中药联合卡培他滨同步维持治疗晚期结直肠癌

目的评价复方中药联合卡培他滨在晚期结直肠癌维持期的疗效。方法将符合晚期结直肠癌维持治疗诊断标准的100例患者随机分为治疗组和对照组,各50例。治疗组:卡培他滨按照每日总剂量(常规用量每2 000mg/m2)分早、晚各1次,饭后30min口服,同步复方中药每日1剂,分2次,早、晚饭后1h服用。连续用药2周停药1周。对照组:单服卡培他滨。2组均持续用药至肿瘤进展或出现无法耐受的不良反应为止。结果治疗组和对照组的中位无疾病进展时间(PFS)分别为6.4个月和2.5个月,2组比较有显著性差异(P0.05);与对照组比较,治疗组可以明显提高晚期结直肠癌患者的NK细胞及CD4/CD8(P0.05),可以明显改善患者的卡氏评分(P0.01)。结论复方中药联合卡培他滨同步维持治疗晚期结直肠癌具有延长患者PFS、改善免疫功能、提高生活质量的作用。     

卡培他滨中有机残留溶剂的检测

目的建立气相色谱法测定卡培他滨原料药中二氯甲烷、乙醇、甲醇和乙酸乙酯4种有机溶剂。方法采用DB-624毛细管柱,FID检测器,以DMSO为溶剂。结果各有机溶剂的平均加样回收率为93.7%～97.6%,RSD为2.5%～3.7%。结论该方法稳定准确,可用于卡培他滨中有机溶剂残留的检测。