含大剂量表阿霉素的联合化疗方案治疗晚期胃癌

目的　研究含大剂量表阿霉素的联合化疗（ＥＣＬＦ） 方案在治疗晚期胃癌中的作用。　方法　１９９８ 年５月～１９９８ 年１２ 月，３０ 例晚期胃癌随机分组治疗。　结果　大剂量表阿霉素组（９０ ｍｇ／ｍ２ 缓慢静脉推注） 优于常规剂量组（５０ ｍｇ／ｍ２） 。近期有效率分别为５５ ％ 、４０％ ，但Ｐ＞ ００５ 。除腹泻外，两组的Ⅲ～Ⅳ级不良反应均无显著性差异（ Ｐ＞ ００５） 。　结论　含大剂量表阿霉素的联合化疗方案治疗晚期胃癌，能提高疗效。     

Focal therapeutic efficacy of transcatheter arterial infusion of styrene maleic acid neocarzinostatin for hepatocellular carcinoma

We evaluated the focal therapeutic effect of oily carcinostatic agents administered by transcatheter arterial infusion (TAI) as the initial therapy in patients with hepatocellular carcinoma in a randomized controlled clinical trial. Group A (19 patients) received 4 mg of styrene maleic acid neocarzinostatin in 4 ml of Lipiodol, and group B (18 patients) received 100 mg of epirubicin in 4 ml of Lipiodol via the tumor feeding arteries as peripherally as possible. The grade of Lipiodol accumulation and the tumor regression rate were determined 2 weeks after TAI by computerized tomography. Adverse effects within 2 weeks after TAI were evaluated by subjective signs and symptoms such as fever (maximum body temperature) and the frequency of shaking chills and abdominal pain, and by biochemical parameters such as albumin, prothrombin time, and aspartate and alanine aminotransferases. Lipiodol accumulation in the tumor was significantly greater in group A (12/19; 63.2% showing grade IV Lipiodol accumulation) than in group B (3/18; 16.7% showing grade IV) (P < 0.05). The tumor regression rate was also significantly greater in group A (8/17; 47.1% showing more than 25% tumor regression) than in group B (1/13; 7.7% showing more than 25% tumor regression) (P < 0.05). Although clinically significant elevations of aminotransferases and reductions of cholinesterase, and shaking chills were observed more often in group A than in group B (P < 0.0001), these factors had little influence on the clinical outcome. Our results suggest that styrene maleic acid neocarzinostatin in Lipiodol exerts a more favorable focal therapeutic effect than does epirubicin in Lipiodol in the initial treatment of hepatocellular carcinoma. Received: February 15, 1999 / Accepted: July 23, 1999     

Efficacy and safety of epirubicin and etoposide combination chemotherapy in advanced hepatocellular carcinoma: a retrospective analysis

Background and Aim: Systemic treatments of advanced hepatocellular carcinoma (AHCC) have offered marginal clinical benefits. Recently, Italian investigators reported that etoposide and epirubicin combination (EE) chemotherapy was highly active against AHCC, with a response rate of 39% and a median overall survival (OS) of 10 months. We report our efficacy and safety results of EE in clinical practice. Methods: Between December 1999 and October 2005, 35 patients with AHCC and fitting the preset eligibility criteria were treated with EE. Twenty‐eight patients (80%) had liver disease associated with hepatitis B virus (HBV) and 26 (74%) had a prior history of transarterial chemoembolization (TACE) using cisplatin. The EE chemotherapy consisted of epirubicin 40 mg/m² on day 1 and etoposide 120 mg/m² on days 1, 3 and 5 every 4 weeks. Results: A total of 102 chemotherapy cycles were administered, with a median of two cycles per patient (range one to eight cycles). Two patients had a partial response and nine had stable disease, with a tumor control rate of 32% (95% CI 17–48). The median progression‐free survival (PFS) was 2.1 months (95% CI 1.8–2.4) and the median OS was 6.4 months (95% CI 4.4–8.5). There was a tendency toward improved PFS in patients seronegative for HBsAg and peritoneal seeding (P = 0.06 and P = 0.054, respectively). Overall survival was significantly better in patients without HBsAg and Cancer Liver Italian Program (CLIP) score 0–1 (P = 0.024 and P = 0.033, respectively). The main toxicities were hematological events, including grade 3/4 neutropenia in 29% and febrile neutropenia in 11% of patients. Conclusion: Treatment with EE showed minimal antitumor activity with acceptable toxicity in HBV‐associated AHCC, especially in patients pretreated with TACE.     

ECF与DOF方案治疗晚期胃癌的临床疗效观察

目的：观察ECF方案（表柔比星联合顺铂、氟尿嘧啶）和DOF方案（多西他赛联合奥沙利铂、氟尿嘧啶）治疗晚期胃癌的临床疗效和不良反应。方法将68例确诊为晚期胃癌患者分为两组,其中ECF组30例,DOF组38例,ECF方案：表柔比星50mg／m2第1天,顺铂20mg／m2第1～3天,氟尿嘧啶500mg／m2第1～5天;DOF方案：多西他赛75mg／m2第1天,奥铂130mg／m2第1天,氟尿嘧啶500mg／m2第1～5天。21d为1个周期,两组均治疗2个周期以上。根据WHO的标准评价其有效性和毒性。结果68例患者均可评价疗效,ECF组有效率为46．67％（14／30）,DOF组有效率为42．11％（16／38）。不良反应主要为骨髓抑制、胃肠道反应、脱发、神经毒性等,DOF组神经毒性发生率39．47％（15／38）高于ECF组的13．33％（4／30）,ECF组恶心呕吐发生率93．33％（28／30）高于DOF组的68．42％（26／38）,两组比较差异有统计学意义（P＜0．05）。结论ECF方案与DOF方案对晚期胃癌的疗效相似,不良反应可以耐受。     

Weekly epirubicin plus docetaxel as first-line treatment in metastatic breast cancer

This study was designed to evaluate the efficacy and tolerability of a weekly schedule of epirubicin in combination with docetaxel in the first-line treatment of patients with metastatic breast cancer (MBC). A total of 43 women with MBC not previously treated with chemotherapy for metastatic disease received weekly epirubicin 25 mg m(-2) and docetaxel 25 mg m(-2) for a maximum of five cycles (total cumulative epirubicin dose of < or =900 mg m(-2)). Dose reduction was not permitted. Objective response and evaluation of toxicity profile were the primary study end points; time to progression and overall survival were secondary end points. Patients were followed for a median of 21 (4-38) months. Analysis was by intent to treat; 33 patients completed five cycles of therapy, and the median dose of epirubicin administered to the 43 patients was 23 mg m(-2). Twenty-five patients (58%) achieved a partial response and one (2%) achieved a complete response. An additional 12 patients (28%) had stable disease. The median time to progression was 11 months (95% confidence intervals (CI) 7-14) overall, and 13 months (95% CI 12-14) in the 26 patients who responded to treatment. Median overall survival was 25 months for responders and 14 months for nonresponders. Grade 3/4 neutropenia occurred in 16% of patients and in 6% of cycles. One patient developed cardiac toxicity (20% reduction in left ventricular ejection fraction). The combination of epirubicin plus docetaxel is highly active in MBC, with a manageable toxicity profile. Such a weekly schedule might provide a valuable treatment option for MBC.     

Oxaliplatin, 5-fluorouracil/leucovorin and epirubicin as first-line treatment in advanced gastric carcinoma: a phase II study

The association between oxaliplatin and 5-fluorouracil (5-FU) has been extensively reported to improve prognosis of gastric cancer patients. The present study is aimed at evaluating response rate and the toxicity profile of the association with oxaliplatin, 5-FU/lecovorin and epirubicin in gastric cancer patients with locally advanced or metastatic disease. Thirty-six patients have been enrolled and 35 evaluated. The treatment schedule was oxaliplatin (100 mg m(-2)), 5-FU (400 mg m(-2)), leucovorin (40 mg m(-2)) and epirubicin (60 mg m(-2)) intravenously. administered every 3 weeks for 6 months, for a total of 185 therapy cycles . Response rate and toxicity were assessed according to the international WHO criteria. Every patient received a mean of 5.3 therapy cycles in a day-hospital setting. Sixteen of 35 patients (46%) showed an objective response, two complete response and 14 partial response. Median time to progression was 33 weeks with an overall median survival of 49 weeks. During the study, anaemia grade 3 and neutropenia grade 3 were observed in 9 and 11% of patients respectively. A grade 3 periferic sensorial neuropathy was observed in 6% of patients. No life threatening or cardiac toxicity was recorded. The regimen used showed anticancer activity against gastric carcinoma, a tolerable toxicity profile and excellent patient compliance.     

The preliminary evaluation on cholesterol-modified pullulan as a drug nanocarrier

Abstract

To further develop cholesterol-modified pullulan self-aggregated nanoparticles (CHSPNs) as a drug nanocarrier, CHSP was synthesized and characterized. Its cholesterol degree determined by ¹H NMR was 5.2 cholesterol groups per hundred glucose units. CHSPNs were prepared in aqueous media and characterized by dynamic laser light-scattering (DLS), zeta potential and transmission electron microscopy (TEM). These nanoparticles were almost spherical in shape, and the zeta potentials of CHSPNs were near zero in aqueous media. CHSPNs can be stable at least 2 months with no significant size and zeta potential changes. Single dose toxicity test in mice was investigated for the safety evaluation of CHSPNs as a drug nanocarrier, and the result showed CHSPNs were well tolerated at the dose of 200?mg/kg in mice. Epirubicin (EPI)-loaded CHSPNs (EPI-CHSPNs) were prepared and the in vivo pharmacokinetics and biodistribution were studied. Compared with the EPI solution, EPI-CHSPNs have exhibited higher plasma drug concentration, longer half-life time (t_1/2) and the larger area under-the-curve (AUC). Moreover, the drug level of EPI-CHSPNs increased in liver and decreased in heart. The results indicated that CHSPNs were stable, safe and may be a promising drug delivery carrier.     

Phase I, dose-finding study of capecitabine in combination with docetaxel and epirubicin as first-line chemotherapy for advanced breast cancer.

PURPOSE: Capecitabine is an oral fluoropyrimidine with considerable activity and minimal myelosuppression and alopecia. This phase I study evaluated the addition of capecitabine to epirubicin/docetaxel combination therapy as first-line treatment for advanced breast cancer. PATIENTS AND METHODS: Twenty-three female patients with advanced breast cancer received capecitabine (765-1060 mg/m2 twice daily on days 1-14 of a 3-week treatment cycle) in combination with epirubicin and docetaxel (75 mg/m2 i.v. on day 1). RESULTS: The maximum tolerated dose of capecitabine was 985 mg/m2 and the principal dose-limiting toxicity was febrile neutropenia. No grade 3/4 anemia or thrombocytopenia occurred. There were no grade 4 non-hematological events and grade 3 events other than alopecia were rare. Alopecia occurred in all patients and treatment cycles, and asthenia occurred in all patients and in 84% of treatment cycles. Other frequent adverse events included nausea, vomiting, fever, paresthesia and elevated transaminase levels. An objective response to treatment was observed in 91% (95% confidence interval 72% to 99%) of patients. CONCLUSIONS: The addition of capecitabine to docetaxel/epirubicin combination therapy provides a well-tolerated and active first-line chemotherapy regimen in patients with advanced breast cancer, and merits phase II/III evaluation.     

含草酸铂方案治疗晚期胃癌近期疗效分析——附18例报告

目的 :观察甲酰四氢叶酸钙 (CF)与 5 氟脲嘧啶 (5 FU)合用草酸铂 (OXA)和表阿霉素 (EPI)作为一线方案治疗晚期胃癌的疗效和毒性。方法 :共收治Ⅳ期胃癌 18例 ,其中低分化腺癌 10例 ,中分化腺癌 3例 ,黏液腺癌 3例 ,印戒细胞癌 2例。初治 15例 ,复治 3例。方案包括CF 15 0mg m2 静脉滴入 2h ,第 1～ 5天 ,5 FU 375mg m2 持续静脉滴入 ,连续 12 0h ;国产草酸铂 80～ 10 0mg m2 静脉滴入 2h ,第 1天 ;EPI 60mg m2 静脉推注 ,第 1天 ;3～ 4周为 1个周期。结果 :CR 1例 ,PR 10例 ,NC 5例和PD 2例 ,总有效率 (CR PR)为 61 1% (11 18)。中位缓解期 8个月 ,中位生存期 11个月 ,1年生存率为4 5 %。主要毒副反应为骨髓抑制和脱发。骨髓抑制为剂量限制性毒性 ,其中Ⅲ～Ⅳ度占 2 2 2 % ,需要配合G CSF的应用。 1例发生Ⅰ度腹泻和 1例发生Ⅰ度外周神经病变 ,未作特殊处理。结论 :LFOE方案是治疗晚期或转移性胃癌高效且较安全的方案