EP方案与分段加速超分割放疗联合治疗局部晚期非小细胞肺癌的研究

目的 观察EP方案与分段加速超分割放疗联合应用对局部晚期非小细胞肺癌的疗效和毒副作用。方法顺铂30mg/m^2和足叶乙甙60mg/m^2，静脉滴注，第1～3天；第4～8天行分段加速超分割放疗，每次1．5Gy，每日2次，2次间隔最少6h，每周期共15Gy，4周为一个周期。其中第3周期的第11～15天加用常规放疗，每日1次，每次2Gy，使放疗总剂量达55Gy。联合放化疗3周期后，再应用MVP方案化疗2周期。结果43例患者中，CR12例,PR22例，NC5例，PD4例，有效率为79.1％。在152个治疗周期中，40个周期发生Ⅲ～Ⅳ度毒性反应，主要为白细胞减少和呕吐。1年生存率为66．7％，2年生存率57．2％。结论EP方案与分段加速超分割放疗联合治疗局部晚期非小细胞肺癌有效率高,患者生存期长，毒副作用能够耐受，值得进一步研究。     

Phosphorylation of Fas-associated Death Domain Contributes to Enhancement of Etoposide-induced Apoptosis in Prostate Cancer Cells

Fas-associated death domain (FADD) plays an important role as an adapter molecule in Fas (CD95/APO-l)-mediated apoptosis and contributes to anticancer drug-induced cytotoxicity. We treated three human prostate cancer cell lines with etoposide, a toposiomerase II inhibitor with activity against various tumors including prostate cancer. We found that the overexpression of FADD sensitizes etoposide-induced apoptosis through a rapid activation of c-Jun NH₂-terminal kinase (JNK) and, subsequently, of caspase 3. In addition, phosphorylation of FADD at serine 194 coincided with this sensitization. Treatment with the caspase 3 inhibitor, N-acetyl-Asp-Glu-Val-Asp-aldehyde (DEVD-CHO), or overexpression of either mitogen-activated protein kinase kinase (MKK) 7 or Bcl-xL canceled FADD-mediated sensitization to etoposide-induced apoptosis. Moreover, treatment with the caspase 8 inhibitor, benzyloxy-carbonyl-Val-Ala-Asp-fluoromethylketone (z-IETD-fmk), or overexpression of viral FLICE/caspase-8-inhibitory protein (FLIP) from equine herpesvirus type 2 E8 also had an inhibitory effect, supporting a major involvement of a caspase 8-dependent mitochondrial pathway. Interestingly, FADD was phosphorylated, and etoposide-induced JNK/caspase activation and apoptosis were enhanced in the cells arrested at G2/M transition, but not in those overexpressing mutant FADD, in which 194 serine was replaced by alanine. Our results demonstrate that phosphorylated FADD-dependent activation of the JNK/caspase pathway plays a pivotal role in sensitization to etoposide-induced apoptosis in prostate cancer cells.     

应用EPB方案治疗复发性非何杰金氏淋巴瘤的疗效观察

 本文报告应用EPB方案，即足叶乙甙，顺铂、平阳霉素治疗24例Ⅲ、Ⅳ期复发性非何杰金氏淋巴瘤。所有病例经病理组织学证实。中度恶性10例，高度恶性14例。全组总缓解率75%，其中完全缓解率25%(6例)，部分缓解率50%(12例)。毒性反应主要为白细胞减少和消化道反应。大部分病人均能耐受，无致死性毒副反应发生。     

A Ureteral Small Cell Carcinoma Mixed with Malignant Mesodermal and Ectodermal Elements: A Clinicopathological, Morphological and Immunohistochemical Study

A 60-year-old male with a small cell carcinoma of the rightlower ureter is presented. The tumor mainly comprised a smallcell carcinoma but also included a full variety of histologicaltypes such as transitional cell carcinoma, squamous cell carcinoma,adenocarcinoma, leiomyosarcoma and chondrosarcoma. Immunohistochemicalstaining was positive for neuron specific enolase and cluster1 small cell lung cancer antigen/N-CAM in the small cell carcinomaand S-100 in the chondrosarcoma component. The patient underwenta right nephroureterectomy, and received prophylactic radiationof the pelvic and para-aortic lymph node regions and cisplatinand etoposide combination chemotherapy. Eight months after thechemotherapy, a transitional cell carcinoma was found in thebladder neck, and a cystectomy with urethrectomy performed.To our knowledge, this is the second report of a small cellcarcinoma originating from the ureter.     

Adjuvant therapy of completely resected dysgerminoma with carboplatin and etoposide: a trial of the Gynecologic Oncology Group

OBJECTIVE: This study was designed to evaluate the effect of adjuvant chemotherapy with carboplatin and etoposide in patients with completely resected stage IB-III dysgerminoma. METHODS: Eligible patients were treated with three courses of carboplatin 400 mg/m(2) on day 1 plus etoposide 120 mg/m(2) on days 1, 2, and 3 every 4 weeks for three courses. RESULTS: Forty-two patients were entered on this trial, of whom 39 were eligible. No patient suffered a recurrence of dysgerminoma, but one patient ultimately died of lung adenocarcinoma. One patient was excluded on pathology review (elements of endodermal sinus tumor were present) developed recurrent tumor and died despite further therapy. As expected, the regimen was well tolerated. Median follow-up of surviving patients is 7.8 years (range: 2.86 months to 10.92 years). CONCLUSION: The regimen used in this study is an alternative to cisplatin, etoposide, and bleomycin (BEP) for selected patients for whom minimizing toxicity (particularly neuropathy) is critical or for whom reduction in the number of treatment days is important.     

Effect of a novel somatostatin analogue combined with cytotoxic drugs on human tumour xenografts and metastasis of B16 melanoma

A novel somatostatin analogue, TT-232 (which inhibits the proliferation of various cell cultures and transplantable mouse tumours), was examined regarding its effect on human melanoma and lymphoma xenografts as a single treatment or in combination with DTIC (dacarbazine) and etoposide. TT-232 inhibited the growth of HT-18 melanoma xenografts, a dose of 5 mg kg(-1) being the most effective. Combination of 1 mg kg(-1) TT-232 with 30 or 60 mg kg(-1) DTIC (administered daily) resulted in a stronger inhibitory effect compared to TT-232 or DTIC as a single modality. Antimetastatic effect of TT-232 treatment combined with DTIC was studied using the B16 mouse melanoma muscle - lung metastasis model. The number of lung metastases of B16 melanoma could be decreased by the daily administration of 1 mg kg(-1) TT-232 or 60 mg kg(-1), but not of 30 mg kg(-1) DTIC. TT-232, combined with 30 or 60 mg kg(-1) DTIC decreased the lung metastasis number significantly lower than the control. Nearly 50% growth inhibition of HT-58 lymphoma was achieved by daily treatment with 1 mg kg(-1) TT-232. 5 mg kg(-1) etoposide, administered daily, resulted in a similar effect. The combination of 1 mg kg(-1) TT-232 and 5 mg kg(-1) etoposide was significantly more effective than TT-232 or etoposide as a single treatment. The very strong tumour growth inhibitory effect of 10 mg kg(-1) etoposide could even be increased by combination with TT-232. These experimental data suggest that TT-232 may be an effective new tool in the combination chemotherapy of malignant tumours like melanoma and lymphoma.     

环磷酰胺或足叶乙甙联合粒细胞集落刺激因子动员自体外周血造血干细胞的对照研究

背景与目的:通过动员采集获得高质量的自体外周血造血干细胞(autologousperipheralbloodstemcell,APBSC)是造血干细胞移植成功的关键,环磷酰胺(cyclophosphamide,CTX)联合重组人粒细胞集落刺激因子(recombinedhumangranulocytecolony-stimulatingfactor,rhG-CSF)是APBSC经典的动员方案,足叶乙甙(etoposide,VP-16)联合rhG-CSF是近年来应用的另一个动员方案。本研究的目的是比较上述两种动员方案对恶性淋巴瘤和生殖细胞肿瘤患者APBSC的动员效果。方法:共有52例恶性实体瘤患者,其中CTX方案组26例,剂量为CTX3.5g/m2加rhG-CSF5μg·kg-1·d-1;VP-16方案组26例,VP-16的剂量随机采用1000mg/m2或1500mg/m2加rhG-CSF5μg·kg-1·d-1。两组均在白细胞(whitebloodcell,WBC)降至最低点时开始皮下注射rhG-CSF,直至采集结束前一天。当CTX组WBC恢复到2.5×109/L、VP-16组WBC恢复到5.0×109/L以上时开始连日采集APBSC,当累计采集的单个核细胞(mononuclearcell,MNC)≥5×108/kg或CD34+细胞≥2×106/kg时停止采集。患者经预处理后回输采集到的APBSC。比较两组动员采集过程中的血液学指标变化、采集细胞数量、造血重建时间、不良反应等。结果:CTX组患者化疗后外周血中WBC和血小板(platelet,PLT)降至最低值的时间明显早于VP-     

A limited-sampling strategy for estimation of etoposide pharmacokinetics in cancer patients

Etoposide (VP16), a widely used anticancer drug, is a topoisomerase II inhibitor. A number of studies have highlighted a correlation between hematologic toxicity and pharmacokinetic or physiological parameters. Other studies have also suggested that the anti-tumor response could be related to the plasma etoposide concentration. Therefore, it would seem of interest to individualize VP16 dose regimens on the basis of pharmacokinetic parameters. The aim of this study was to develop and validate a limited-sampling strategy allowing VP16 pharmacokinetic evaluation with minimal disturbance to the patient. A total of 34 patients (54 kinetics) received VP16 at various dose regimens, with doses ranging between 30 and 200 mg and infusion times varying between 0.5 and 2 h. The statistical characteristics of the pharmacokinetic parameters were assessed from the first courses of treatment performed in 23/34 patients; then the following three-sample protocol was designed: the end of the infusion and 5 and 24 h after the start of the infusion. For validation of the model the main pharmacokinetic parameters (clearance, half-lives, volume of distribution) were estimated in the 11 remaining patients by maximum-likelihood estimation (ML) and by Bayesian estimation (BE) using the three sampling times designed. Statistical comparison showed a good concordance between ML and BE estimates (the bias for clearance was –1.72%). The limited-sampling strategy presented herein can thus be used for accurate estimation of VP16 pharmacokinetic parameters. Received: 17 November 1997 / Accepted: 25 August 1998     

EAP／LF交替方案治疗进展期胃癌的临床研究

目的：探讨EAP／LF交替方案进展胃癌的疗效。方法：自1994年10月至1999年12月，124例经病理确诊的有可测量病灶的进展期胃癌患者被随机分入EAP／LF组（研究组）和EAP组（对照组），研究组用药为：足叶乙甙（Vp-16)70mg/m^2，静滴，d4-6；阿霉素（ADM）15mg/m^2，静注d1.7；顺铂（DDP）20mg/m^2，静滴，d2．8，醛氢叶酸（CF）70mg/m^2，静滴，d29－33，5－氟尿嘧啶（5－FU）325mg/m^2，静滴，d29－33，每8周重复，。结果：研究组客观有效率为62．1％，明显优于对照组的48．3％（P＝0．032）；研究组有效者中位生存期、无进展生存时间分别为20个月、13个月，均明显优于对照组13个月（P＝0．037）、7个月（P＝0．007）。两组不良反应主要有白细胞减少、口腔粘膜炎、脱发、结论：调整剂量的EAP／LF交替方案是一疗效确切，安全、对生存有益处的治疗进展期胃癌的优势方案，值得临床进一步研究。