周剂量多西紫杉醇、奥沙利铂联合低剂量氟尿嘧啶方案治疗晚期胃癌的临床观察

目的：研究周剂量多西紫杉醇、奥沙利铂联合低剂量氟尿嘧啶（5-FU）持续滴注治疗晚期胃癌的近期疗效和毒副作用。方法：晚期胃癌31例，应用多西紫杉醇40mg／m^2，静滴1小时，每周1次，连用2周；奥沙利铂70mg／m^2，静滴2小时，每周1次，连用2周；5-FU200mg／m^2，连用14天。以上化疗方案每4周重复，2周期后评定疗效。结果：31例晚期胃癌总有效率67．7％，其中CR2例，PR19例。主要毒性反应为骨髓抑制、消化道反应、脱发等。结论：多西紫杉醇、奥沙利铂作为新的抗胃癌药物，联合低剂量5-FU持续滴注对晚期胃癌近期效果显著，毒副反应较小，可以作为晚期胃癌的一种选择方案。     

多西他赛联合希罗达治疗复发转移性乳腺癌的临床观察

目的:对于复发转移性乳腺癌,多西他赛和希罗达药物均有确切肯定的疗效,由于多西他赛能增强肿瘤组织的胸苷磷酸化酶(TP)活性,因而与希罗达有协同作用。本研究观察及评价多西他赛联合希罗达治疗复发转移性乳腺癌的疗效和不良反应。方法:32例复发转移性乳腺癌患者均给予多西他赛75mg/m2,第1天;希罗达口服2次/d,餐后服用,每次1250mg/m2,连续服用14d,治疗周期为21d,至少治疗2个周期。结果:本组完全缓解(CR)2例,部分缓解(PR)15例,稳定(SD)4例,疾病进展(PD)10例,总有效率53.1%,中位疾病进展时间(TTP)10个月。不同转移部位或器官的有效率分别为:软组织62.7%(10/16);肺脏50%(9/18);骨骼54.5%(6/11);肝脏30.0%(7/13)。常见不良反应为手足综合征、皮肤色素沉着、恶心、呕吐、厌食、疲劳,少数患者出现口炎、头晕、腹泻和胸闷。90.6%的患者有白细胞下降,2例Ⅳ度骨髓抑制。结论:多西他赛联合希罗达治疗晚期乳腺癌疗效肯定,患者耐受性良好。     

Docetaxel and paclitaxel inhibit DNA-adduct formation and intracellular accumulation of cisplatin in human leukocytes

 The purpose of this study was to determine the mechanism of the pharmacodynamic interaction between docetaxel/paclitaxel and cisplatin. Cisplatin-induced DNA-adducts and cisplatin accumulation were quantitated in peripheral blood leukocytes (WBC). The WBC were obtained from patients treated with docetaxel or paclitaxel in phase I/II studies and were incubated in vitro with cisplatin. In addition, blank whole-blood samples were obtained from patients and healthy subjects and incubated in vitro with cisplatin or docetaxel/paclitaxel and cisplatin. The cisplatin-induced DNA-adduct levels measured in WBC after treatment with docetaxel or paclitaxel were significantly lower than those determined in non-pretreated WBC. Docetaxel and paclitaxel reduced the intracellular accumulation of cisplatin in WBC by 46–47%. If the pharmacodynamic interaction between docetaxel/paclitaxel and cisplatin also occurs in other normal tissues such as bone marrow, it may well contribute to the sequence dependent toxicity that has been observed in clinical studies. Received: 15 February 1995/Accepted: 6 June 1995     

多西紫杉醇加顺铂及氟尿嘧啶化疗辅助治疗进展期胃癌

目的研究多西紫杉醇加顺铂及氟尿嘧啶(5-FU)/亚叶酸钙方案联合新辅助化疗治疗局部进展期胃癌,并评价此方案的疗效和毒副作用。方法2003-10～2004-10收治的18例局部进展期胃癌患者加入研究。入组患者术前接受的新辅助化疗方案为:多西紫杉醇75mg/m2,第1天静脉滴注;顺铂30mg/m2,第1～3天静脉滴注;5-FU500mg/m2,第1～5天静脉滴注;亚叶酸钙100mg于5-FU前30min静脉冲入;每3周为1周期,共3个周期。观察新辅助化疗后肿瘤原发病灶的缓解情况、手术后病理缓解情况以及新辅助化疗的毒副反应。结果新辅助化疗后所有患者进行了根治性手术治疗,有效10例,其中完全缓解3例,部分缓解7例;疾病稳定5例,疾病进展3例。术后病理检查2例病理水平达到完全缓解。不良反应主要为白细胞减少、恶心、脱发、呕吐及黏膜炎,其中有4例患者发生了Ⅲ～Ⅳ级的白细胞减少,但未有因此而发生严重感染和病死者。结论多西紫杉醇加顺铂及5-FU/亚叶酸钙的化疗方案在进展期胃癌的治疗中近期疗效显著,患者耐受性良好。     

Effects of paclitaxel, docetaxel and their combinations on subcutaneous lymphomas in inbred Sprague–Dawley/Cub rats

We investigated, whether the effects on paclitaxel, docetaxel or their combinations on T-cell lymphomas in Sprague-Dawley/Cub rats were mainly caused by their different efficiency or combination of different mechanism of action, or limited by metabolic inactivation by P450 enzymes or drug efflux caused by P-glycoprotein (P-gp). Docetaxel most effectively prolonged the survival of rats and the time of lymphoma appearance, inhibited their intravital size and weight after sacrifice. Paclitaxel was poorly effective and combined administration had intermediate effects. Blood levels of both drugs were similar. Repeated administration of paclitaxel, but not docetaxel, decreased its area under concentration, but the effect disappeared 6h after dosing and was not sufficient to explain lower effects of paclitaxel. The faster metabolism of docetaxel than paclitaxel in vitro did not limit its higher efficiency and repeated administration of paclitaxel did not induce its metabolism to decrease its blood levels sufficiently. Likewise, undetectable expression of P-gp protein in tumours could not explain lower effects of paclitaxel, which is a better substrate of P-gp. Docetaxel was three-fold more effective than paclitaxel against P388D1 lymphoma cell line, used as a model of the T-cell lymphoma and combined action was dominated by the effects of docetaxel. Thus, docetaxel was effective against T-cell lymphomas and may be a potential anticancer drug in similar indications.     

多西紫杉醇联合顺铂2周方案治疗晚期非小细胞肺癌临床观察

目的探讨多西紫杉醇联合顺铂2周给药一线治疗晚期非小细胞肺癌(NSCLC)的疗效及毒副作用。方法多西紫杉醇75mg/m2静脉滴注,顺铂25mg/m2×3d静脉滴注联合化疗,每2周重复疗程。化疗期间用粒细胞-集落刺激因子预防性支持治疗。结果共39例晚期NSCLC患者完成化疗,36例可评价疗效,其中完全缓解1例(2.8%),部分缓解13例(36.1%),稳定21例(58.3%),进展1例(2.8%);总有效率38.9%。本方案化疗所致毒性反应主要为骨髓抑制,恶心、呕吐,肌肉、关节痛,脱发和疲劳。结论多西紫杉醇联合顺铂2周给药是治疗晚期NSCLC的有效可行方案,其毒副作用患者可耐受,值得进一步研究。     

多西紫杉醇联合顺铂治疗蒽环类耐药的晚期乳腺癌

目的:观察多西紫杉醇(DXL)联合顺铂(DDP)方案对蒽环类耐药的晚期乳腺癌患者的临床疗效及毒副作用。方法:2000年1月～2004年6月采用DXL联合DDP方案治疗晚期乳腺癌患者45例。DXL60mg/m2,静脉滴注,第1天;DDP30mg/m2水化后静脉滴入,第1～3天,每28天重复,至少应用2个周期,中位化疗周期数3个(2～6周期)。结果:45例患者中,CR、PR及SD率分别为11.1%(5/45)、40.0%(18/45)和22.2%(10/45),总有效率为51.1%(23/45),疾病控制率为73.3%(33/45)。45例患者中22例死亡,中位无进展生存时间为7.8(1.0～34.5)个月,中位生存时间为17.6个月(1.9～48.0月),1年生存率为65.2%。主要不良反应为骨髓抑制。结论:DXL联合DDP方案治疗蒽环类耐药的晚期乳腺癌疗效好,不良反应轻,是治疗蒽环类耐药的晚期乳腺癌较好的方案。     

Docetaxel, 5-fluorouracil, and leucovorin as treatment for advanced gastric cancer: results of a phase II study

Background: Previous studies have shown that the taxane, docetaxel, is effective in treating gastric cancer. The aim of this study was to assess the efficacy and safety of docetaxel in combination with 5-fluorouracil (5-FU) and leucovorin (LV). Methods: Thirty patients with histologically proven locally advanced and/or metastatic gastric cancer with WHO performance status 0–2 were enrolled and received either 75 or 100 mg/m² docetaxel as a 1-h intravenous infusion on day 1 every 28 days. All patients also received 5-FU (1800 mg/m²) plus LV (500 mg/m²), by continuous intravenous infusion over 24 h on days 1, 8, and 15 every 28 days. Chemotherapy was given for at least two cycles. Results: Of the 25 evaluable patients, 3 showed a complete response, 4 showed a partial response, and 11 patients had stable disease. The overall response rate was 28.0% (95% confidence interval [CI], 10.4, 45.6). The median time to progression was 5.9 months (95% CI, 5.4, 6.5), and the median overall survival was 7.7 months (95% CI, 7.2, 8.3) for the intent-to-treat population. The most frequent grade III and IV hematological toxicities were neutropenia and anemia. Febrile neutropenia was observed in 10% of patients and 2.4% of cycles. The prophylactic use of granulocyte colony-stimulating factor (G-CSF) in 3 patients reduced the incidence and severity of neutropenia. Other hematological toxicities were rare. Conclusion: Docetaxel in combination with weekly 5-FU and LV is effective in treating patients with advanced/metastatic gastric cancer. This new docetaxel-containing combination shows promise as a third-generation treatment option for gastric cancer. Received: December 25, 2001 / Accepted: April 22, 2002 Offprint requests to: M. Constenla     

Effectiveness of doxifluridine (5′-DFUR)/docetaxel against advanced/recurrent gastric cancer showing resistance to various anticancer drug regimens

A 58-year-old man was diagnosed as having type 3 gastric cancer (poorly differentiated adenocarcinoma). He underwent total gastrectomy with splenectomy, as well as D3 dissection, and received postoperative chemotherapy combining oral uracil and futrafur (UFT) with cisplatin (CDDP), but results showed recurrence of multiple abdominal lymph node metastases around the aorta. He therefore received various anticancer drug regimens (irinotecan [CPT-11]/CDDP; 1 M tegafur-0.4 M gimeracil-1 M oteracil potassium [TS-1], methotrexate (MTX)/5-fluorouracil); however, final results showed growth of lymph node metastasis and simultaneous worsening of his general condition. The patient then received combined administration of doxifluridine (5′-DFUR)/docetaxel (5′-DFUR, 1000 mg/body [666.7 mg/m ² ], given by consecutive daily administration, orally, for days 1–14; and docetaxel, 80 mg/body [60 mg/m ² ], on day 8, by venous drip, every 3 weeks). Three courses of this regimen resulted in approximately 90% reduction of the abdominal lymph node size, disappearance of the right cervical lymph node metastasis, reductions of the levels of two tumor markers (carcinoembryonic antigen [CEA] and carbohydrate antigen [CA]19-9), and improvement of his general condition. In total, seven courses of the regimen were carried out. The patient died on day 298 after starting this combined regimen and showed a response period of 126 days. The primary toxicity identified was neutropenia (grade 4), as well as other low-grade (grade 1, 2) hematological and nonhematological toxicities. In the field of gastric cancer treatment, especially for patients showing multiple resistance to anticancer drugs, an effective therapy is critically needed. Received: January 15, 2002 / Accepted: July 8, 2002 Offprint requests to: A. Sato