表阿霉素联合化疗方案治疗29例恶性肿瘤疗效观察

目的观察以表阿霉素为主的不同化疗方案对常见恶性肿瘤的疗效及其毒副作用。方法以表阿霉素为主的CEP、CEOP、TE、IEO方案治疗肺癌、非霍奇金淋巴瘤、晚期乳腺癌和横纹肌肉瘤，其中表阿霉素60mg/m^2分2天静脉注射，其他药物都为常规剂量。21～28天为1个治疗周期，治疗2～3个周期后评价疗效。结果全组29例中CR7例，PR13例，SD5例，PD4例，总有效率68．97％。主要不良反应为骨髓抑制，其次是脱发和消化道反应。对肝肾功能和心脏影响轻微。结论以表阿霉素为主的联合化疗方案对常见恶性肿瘤疗效佳，安全性好，患者能较好地耐受。     

Anthracycline-induced cardiotoxicity: Overview of studies examining the roles of oxidative stress and free cellular iron

The risk of cardiotoxicity is the most serious drawback to the clinical usefulness of anthracycline antineoplastic antibiotics, which include doxorubicin (adriamycin), daunorubicin or epirubicin. Nevertheless, these compounds remain among the most widely used anticancer drugs. The molecular pathogenesis of anthracycline cardiotoxicity remains highly controversial, although the oxidative stress-based hypothesis involving intramyocardial production of reactive oxygen species (ROS) has gained the widest acceptance. Anthracyclines may promote the formation of ROS through redox cycling of their aglycones as well as their anthracycline-iron complexes. This proposed mechanism has become particularly popular in light of the high cardioprotective efficacy of dexrazoxane (ICRF-187). The mechanism of action of this drug has been attributed to its hydrolytic transformation into the iron-chelating metabolite ADR-925, which may act by displacing iron from anthracycline-iron complexes or by chelating free or loosely bound cellular iron, thus preventing site-specific iron-catalyzed ROS damage. However, during the last decade, calls for the critical reassessment of this “ROS and iron” hypothesis have emerged. Numerous antioxidants, although efficient in cellular or acute animal experiments, have failed to alleviate anthracycline cardiotoxicity in clinically relevant chronic animal models or clinical trials. In addition, studies with chelators that are stronger and more selective for iron than ADR-925 have also yielded negative or, at best, mixed outcomes. Hence, several lines of evidence suggest that mechanisms other than the traditionally emphasized “ROS and iron” hypothesis are involved in anthracycline-induced cardiotoxicity and that these alternative mechanisms may be better bases for designing approaches to achieve efficient and safe cardioprotection.     

Influence of trastuzumab on epirubicin pharmacokinetics in metastatic breast cancer patients.

BACKGROUND: Anthracycline cardiotoxicity is increased by the contemporaneous administration of trastuzumab. The mechanism by which it occurs is as yet unknown. The aim of this study was to evaluate whether trastuzumab modifies the pharmacokinetics of epirubicin and its metabolites. PATIENTS AND METHODS: Women with HER2-positive metastatic breast cancer were treated with epirubicin 75 mg/m(2) i.v. bolus followed by docetaxel 75 mg/m(2) in a 1-h infusion, every 3 weeks for six cycles, and trastuzumab (once at 4 mg/m(2), then 2 mg/m(2) weekly thereafter) in a 30-min infusion. Epirubicin pharmacokinetic data of seven patients were evaluated at the first cycle of therapy (baseline, with trastuzumab administered 24 h after epirubicin), and at the sixth cycle (i.e. 15 weeks after baseline, with trastuzumab administered immediately before epirubicin). RESULTS: No pharmacokinetic change in the parent compound epirubicin was detected. The area under the plasma concentration-time curve (AUC(0-24 h)) was 1230 +/- 318 [mean +/- standard deviation (SD)] at the first cycle and 1287 +/- 385 h. micro g/l at the sixth. The mean (+/-SD) maximum plasma concentration (C(max)) and the terminal elimination half-life at the first cycle (1303 +/- 490 micro g/l and 12.5 +/- 3.1 h, respectively) were similar to those obtained at the sixth cycle (1229 +/- 580 micro g/l and 11.5 +/- 2.9 h, respectively). Pharmacokinetic data of epirubicin metabolites evaluated at the first and sixth cycle of chemotherapy were superimposable without any statistical difference. CONCLUSION: Enhanced anthracycline cardiotoxicity related to trastuzumab administration was not linked to pharmacokinetic interferences with epirubicin and its metabolites.     

4′ -epi-doxorubicin in advanced lung cancer

Summary Fifty evaluable patients with advanced lung cancer (28 small cell and 22 non-small cell carcinomas), mainly pretreated by chemotherapy, received 4-epi-doxorubicin 90 mg/m² every 3 weeks. Two partial responses were obtained in small cell lung cancer patients, which lasted 153 and 168 days. Leukopenia, emesis and alopecia were the most frequent side effects. Two patients who previously received anthracyclines died suddenly of cardiac failure, another patient had severe congestive heart failure, and four others had minor cardiac dysfunctions. 4-epi-doxorubicin has a modest activity in advanced lung cancer, mainly pretreated by chemotherapy and is not devoid of significant cardiotoxicity in this patient population.     

De novo uterine sarcoma with good response to neo-adjuvant chemotherapy

Abstract.  Numa F, Umayahara K, Ogata H, Nawata S, Sakaguchi Y, Emoto T, Kawasaki K, Hirakawa H, Sase M, Oga A, Kato H. De novo uterine sarcoma with good response to neoadjuvant chemotherapy. We report here the extremely rare case of a 28-year-old woman with advanced stage uterine sarcoma arising soon after a cesarean section. She underwent an abdominal cesarean section because of a breech presentation. At the time of the procedure, there were no abnormal findings such as leiomyoma of the uterus in the abdominal cavity. One year later, she was referred to our hospital because of a large abdominal tumor. Transabdominal power Doppler ultrasonography and magnetic resonance imaging (MRI) showed a large hypervascular tumor in the abdominal cavity. Her serum levels, for the two tumor markers carbohydrate antigen CA125 and LDH, were elevated, at 219 U/ml (< 35 U/ml) and 862 IU/l (115 U/ml−217 U/ml), respectively. On the basis of a diagnosis of malignant tumor of gynecological origin, exploratory laparotomy was performed, and through biopsy, the tumor was found to be advanced undifferentiated uterine sarcoma. She exhibited a good response to neoadjuvant chemotherapy consisting of cisplatin, epirubicin, and dimethyltriazenoimidazole carboxamide (DTIC) every 28 days, which was successfully followed by a hysterectomy.     

表柔比星加紫杉醇新辅助化疗方案治疗乳腺癌

目的:研究表柔比星加紫杉醇新辅助化疗方案治疗乳腺癌的近期疗效及毒副反应。方法:用TE方案(紫杉醇加表柔比星)对Ⅱ、Ⅲ期的20例乳腺癌进行新辅助化疗,3-4周为1个周期,患者完成2-4个周期后评价疗效;并以VE方案(长春瑞滨加表柔比星)作对照组进行比较,TE方案:表柔比星(EPI)60 mg/m2,第1天,静脉注射;紫杉醇(TAX)150mg/m2,第2天,静脉点滴;3周为1个周期。VE方案:EPI 60mg/m2,第1天,静脉注射;长春瑞滨(VNR)30mg/m2,第1、8天,静脉注射;4周为1个周期。结果:TE组有效率为80％,其中临床完全缓解(cCR)3例,部分缓解(PR)13例,无变化(NC)4例,病理完全缓解(pCR)2例;VE组有效率为80％,其中cCR 3例,PR 13例,NC 4例,pCR2例。两组均无进展(PD)者。进行4周期新辅助化疗患者有效率高于2周期患者。两组白细胞下降、胃肠道反应、面色潮红和静脉炎等毒副反应相似,VE组乏力、脱发、神经毒性程度比TE组显著(P<0.05),而在关节头痛方面TE组显著(P<0.05)。结论:两组新辅助化疗方案治疗乳腺癌近期有效率较高,疗效相当;VE组毒副反应较TE组高,但均可耐受。     

表柔比星、顺铂与优福定联合治疗晚期胃癌

[目的]探讨表柔比星 (EPI)、低剂量顺铂 (LD DDP)及优福定 (UFT)联合治疗晚期胃癌的客观疗效及毒性反应。[方法]用EPI、LD DDP及UFT(EPU方案 )或DDP、甲酰四氢叶酸钙 (CF)及5氟尿嘧啶 (5 Fu) (PLF方案 )治疗晚期胃癌59例 ,其中EPU组31例 ,PLF组 (对照组 )28例。[结果]EPU组和PLF组的有效率分别为48.4 % (15/31)及39.2%(11/28) ,统计学上无显著差别 (P>0.05)。脱发及血小板减少的发生率EPU组明显高于PLF组 (均P<0.01)。口腔黏膜炎的发生率PLF组明显高于EPU组 (P<0.01)。恶心呕吐、腹泻和白细胞减少的发生率EPU组与PLF组相近 (均P>0.05)。两组发生的毒性反应大多数为Ⅰ～Ⅱ度 ,Ⅲ度者甚少 ,无Ⅳ度者。[结论]EPU方案治疗晚期胃癌有效率较高、毒性颇低 ,应用方便 ,值得进一步研究。     

肝癌患者肝移植术前、术后化疗16例分析

目的:探讨肝癌患者肝移植术前、术后使用希罗达 表阿霉素的可行性、安全性及疗效。方法:回顾性研究16例原发性肝癌患者肝移植前后辅助化疗的临床资料。化疗方案为希罗达2500mg/(m·2d),口服,第1￣14天;表阿霉素20mg/m2,静脉滴注,第1￣2天,分析化疗时机、化疗方案、化疗药物的不良反应及近期疗效。结果:16例接受化疗患者存活时间均超过8个月,最长1例24个月;死亡3例,死亡原因为移植肝肿瘤复发和肝内转移及远处转移,化疗不良反应中,12例出现消化道反应,8例发生骨髓抑制,6例出现手足综合征,4例出现肝功能损害,均为轻中度。结论:肝癌患者肝移植术前、术后化疗联用希罗达 表阿霉素是可行的,不良反应可以耐受,可望延长患者存活时间。选择化疗时机可能对肿瘤复发和患者的生存率有影响。     

Epirubicin, cisplatin and docetaxel combination therapy for metastatic gastric cancer.

BACKGROUND: Docetaxel is a new agent with activity in metastatic gastric cancer. This phase II study was designed to evaluate the activity and safety of an epirubicin, cisplatin and docetaxel combination in patients with this disease. PATIENTS AND METHODS: Forty-six patients with gastric adenocarcinoma with measurable distant metastasis were eligible for the study. Patients received epirubicin 50 mg/m(2) and docetaxel 60 mg/m(2), on day 1, and cisplatin 60 mg/m(2) on day 2. Granulocyte colony-stimulating factor 300 mug/day subcutaneously was given on days 5 and 6. Cycles were repeated every 3 weeks for a maximum of eight courses. RESULTS: All patients were evaluable for response and toxicity. Two complete and 21 partial responses were observed, with an overall response rate of 50% [95% confidence interval (CI) 36% to 64%]. Stable disease was observed in 13 patients (28%) and progressive disease in 10 patients (22%). The median time to progression was 6 months (95% CI 5-7) and the median overall survival was 11.2 months (95% CI 8.5-13.9). Grade 3/4 neutropenia, thrombocytopenia and anemia occurred in 46%, 7% and 13% of patients, respectively. There were five episodes of febrile neutropenia in four patients. Other grade 3 toxicities included mucositis in three patients (6.5%), vomiting in four patients (8.7%) and diarrhea in one patient (2%). There were no cardiac toxicity, severe neurotoxicity or treatment-related deaths. CONCLUSIONS: The epirubicin, cisplatin and docetaxel combination is an active and well tolerated novel chemotherapy regimen for treating metastatic gastric cancer and deserves further evaluation in randomized studies.