Etoposide phosphate, the water soluble prodrug of etoposide

Etoposide (Vepesid) is a widely used drug in a variety of neoplasms. To improve the pharmaceutical characteristics of etoposide, etooside phosphate (Etopophos, Bristol-Myers Squibb) has been developed as a prodrug.Etoposide phosphate is the phosphate ester derivative of etoposide, in comparison to the parent compound, etoposide phosphate is highly soluble in water and can be readily formulated for intravencus uso resulting in higher ctinical application. This paper presents information on the pharmaceutical properties and the current status of etoposide phosphate in clinical triafs.     

In Vivo Accumulation of Etoposide in Peripheral Leukemic Cells in Patients Treated for Acute Myeloblastic Leukemia; Relation to Plasma Concentrations and Protein Binding

Since etoposide interacts with the nuclear enzyme topoisomerase II, the drug concentrations in the malignant cells during chemotherapy may have clinical correlates. Plasma protein binding of etoposide is extensive (94%) and alterations of the non-proteinbound fraction affect pharmacokinetic behavior of the drug. The pharmacokinetics of etoposide was therefore studied in plasma, total and non-proteinbound concentrations, and in leukemic cells isolated from peripheral blood samples from 22 patients after the first dose of the induction treatment for acute myelocytic leukemia. Fourteen patients received 100 mg/m² and eight patients 200 mg/ m² as a 1 h infusion. The mean area under the concentration versus time curve AUC_(0-x) in plasma was at the lower dose level 78.4 ± 29.1 (mean ± S.D.) μg/ml x h and 201.0 ± 56.5 μg/ml x h at the higher dose level. The fraction of non-proteinbound etoposide in plasma was 5.2 ± 3.4 and 5.4 ± 2.1% in the two treatment groups. AUC_(0-16h) in leukemic cells was 8.4 ± 8.7 and 22.4 ± 12.1 μ/ml x h at the two dose levels, respectively. The cellular etoposide concentration was 12.1 ± 7.9 and 14.7 ± 5.1% of the plasma concentration at the end of the infusion. The interpatient variability in cellular drug levels was considerable and exceeded the variability in plasma concentrations. Cellular accumulation of etoposide could be important for treatment outcome.     

CE方案治疗高龄非小细胞肺癌35例效果观察

对３５例高龄（＞６５岁）非小细胞肺癌采用小剂量连续多日给药的ＣＥ方案治疗,观察其疗效和毒副反应。结果ＣＲ２８％,ＰＲ３１４％,总有效率（ＣＲ＋ＰＲ）３４３％。主要副反应为骨髓抑制,消化道及肝肾毒性轻微。认为ＣＥ方案对高龄非小细胞肺癌疗效与其他方案相近,毒副反应轻,可作为高龄非小细胞肺癌的首选方案。     

两种鬼臼脂素衍生物的2DNMR研究

观察睾丸炎期间生精细胞凋亡的情况。方法：Ｇｉｅｍｓａ染色、ＴＵＮＥＬ及流式细胞术测定。结果：经Ｇｉｅｍｓａ染色可见一些生精细胞及巨大核细胞的细胞核染色致密,形状不规则。流式细胞仪测定发现正常小鼠睾丸内亚单倍体很少,模型小鼠睾丸内亚单倍体增多。ＴＵＮＥＬ阳性细胞在模型小鼠睾丸内增多,主要为精原细胞。精母细胞及管腔中的巨大核细胞。结论：正常小鼠睾丸中可见少量凋亡的生精细胞。睾丸炎期间凋亡的生精细胞增多。此时出现的一些巨大核细胞也是凋亡中的细胞。     

Characterization and antitumor efficacy of poly(L-lactid acid)-based etoposide-loaded implants

Etoposide is widely used in the chemotherapy of a variety of malignancies. But the strong lipophilicity, poor bioavailability, and severe side effects of etoposide limit its clinical application. The aim of this study was to develop sustained-release etoposide-loaded implants and evaluate antitumor activity of the implants after intratumoral implantation. We prepared the implants containing etoposide, poly(L-lactid acid) and polyethylene glycol 4000 by the direct compression method. The implants were characterized regarding drug-excipient compatibility, content uniformity, morphology, sterility, in vitro, and in vivo release profiles. Then the antitumor activity of the implants was tested in xenograft model of A549 human non-small cell lung cancer. SEM images displayed smooth surface of the implant and indicated that etoposide was homogeneously dispersed in the polymeric matrix. The results of content uniformity met the requirements of the Chinese Pharmacopoeia. Both in vitro and in vivo release profiles of the implants were characterized by high burst release followed by sustained release of etoposide. Intratumoral implantation of etoposide-loaded implants could efficiently delay the tumor growth. Furthermore, increasing the dose of implants led to higher tumor suppression rate without adding systemic toxicity. These results indicated that etoposide-loaded implants have significant antitumor efficacy in xenograft model without dose-limiting side effects and they possess a strong potential to be used as an intratumoral chemotherapy option for lung cancer treatment.     

ET与EP方案治疗晚期非小细胞肺癌的对比研究

目的 对比ET与EP两组方案治疗晚期非小细胞肺癌的疗效和毒性。方法 通过ET和EP两个联合化学治疗方案每21～28天周期全身给药的方法,共收治晚期非小细胞肺癌65例,其中腺癌42例,鳞癌21例,其他2例。初治41例,复治24例。结果 ET和EP组有效率分别为53.3％(16/30)和28.6％(10/35),两组有显著性差异(P<0.05)。毒副作用主要为骨髓抑制,Ⅲ～Ⅳ度白细胞下降率:ET组为50％(15/30);EP组为25.7％(9/35),两组间有显著性差异(P<0.05),;Ⅲ～Ⅳ度血小板下降率:ET组为6.7％(2/30),EP组为5.7％(2/35);Ⅲ～Ⅳ度消化道反应两组发生率分别为23.3％(7/30)和28.6％(10/35),且以置度为主;ET组Ⅲ度过敏反应2例。结论 ET联合方案对晚期非小细胞肺癌有较好疗效,不良反应可以耐受。     

A case of primary small cell carcinoma of the liver that was treated with chemotherapy

Primary small cell carcinoma (SSC) of the liver is very rare in Japan and only ten cases have been reported worldwide. We report herein the case of a 77-year-old man with primary SCC of the liver. He had a tumor over 10 cm in diameter which was localized in the right lobe of the liver and had invaded the right diaphragm. In laboratory tests, high serum levels of lactate dehydrase and neuron-specific enolase were observed. A biopsy specimen showed that the tumor cells were similar in cytology to a pulmonary SCC. The patient was first treated with carboplatin and etoposide according to the therapy protocol for pulmonary SCC and then with a regimen using etoposid and cisplatinum, resulting in an unfavorable outcome. We discuss the clinical course and therapy of extra-pulmonary SCC and review the literature of the cases previously reported.     

培美曲塞或依托泊苷单药同步放化疗治疗局部晚期老年肺腺癌近期疗效对比研究

目的：探讨培美曲塞或依托泊苷联合同步放化疗治疗局部晚期老年肺腺癌的近期疗效以及急性不良反应。方法方法对经病理证实为IIIA或IIIB期的60例老年肺腺癌患者根据治疗方法分为实验组、对照组,实验组使用培美曲塞[500 mg／（m2?d）],共2个周期;对照组使用依托泊苷[100 mg／d ,d1-d5],共2个周期。化疗同时给予三维适形放疗（3DCRT ）,处方剂量为60Gy ,6周完成。结果有效率（CR＋ PR）实验组为80．0％（24／30）,对照组为73．3％（22／30）,2组差异无统计学意义（P＞0．05）,实验组1年和2年生存率分别为76．7％和56．7％,对照组为73．3％和52．3％,两组无明显差异（ P＞0．05）;不良反应主要包括恶心呕吐、骨髓抑制、肺毒性、食管毒性,其中对照组比实验组组更容易发生中性粒细胞减少,差异有统计学意义（P＜0．05）。结论培美曲塞或依托泊苷联合同步放疗治疗局部晚期老年腺癌近期疗效良好,培美曲塞的不良反应更低,值得临床使用,但从经济学考虑依托泊苷也值得临床推广应用。