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131.
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133.
目的:探讨多西他赛(Docetaxel)联合氟尿嘧啶(5-Fu)、顺铂(DDP)方案治疗晚期鼻咽癌的疗效及不良反应。方法:晚期鼻咽癌患者28例,Docetaxel75mg.(m2)-1静脉滴注,第1天;5-Fu500mg.(m2)-1静脉滴注4h,第1~5天;DDP20mg.(m2)-1静脉滴注第1~5天;3周为1周期,治疗至少2个周期后评价治疗效果。结果:28例患者中,完全缓解3例,部分缓解19例,4例稳定,2例进展,总有效率为78.6%。中位缓解期4.4个月;中位生存期23.6个月。主要不良反应为白细胞减少症、胃肠道反应和脱发。白细胞计数下降总发生率为78.5%,10例患者(35.7%)发生了Ⅲ~Ⅳ级的白细胞减少症,其中3例合并了感染发热。无治疗相关死亡。结论:Docetaxel联合DDP、5-Fu治疗晚期鼻咽癌取得了较好的临床效果,其不良反应比较明显,但在可控制的范围内。 相似文献
134.
目的观察多西他赛(DTX)联合顺铂(DDP)和替加氟(FT-207)对进展期胃癌的近期疗效和不良反应。方法对经病理学或细胞学确诊的24例进展期胃癌患者采用DTX 75mg/m2第1,8天ivgtt,DDP 20mg/m2第1~5天ivgtt,FT-207 500mg/m2第1~5天ivgtt方案化疗,21天为1周期,所有患者均接受至少2个周期治疗后评价疗效。结果全组病例均可评价疗效:CR 1例,PR 12例,SD 5例,PD 6例;近期客观有效率54.2%。其中初治15例,CR 1例,PR 7例,总有效率53.3%;复治患者为9例,CR 0例,PR 4例,总有效率44.4%。主要不良反应为骨髓抑制、恶心呕吐和脱发。结论DTX联合DDP和FT-207治疗进展期胃癌疗效肯定,不良反应轻,耐受性好,初治疗效优于复治,值得临床进一步扩大研究。 相似文献
135.
多西紫杉醇泡囊的大鼠药代动力学研究 总被引:1,自引:0,他引:1
目的采用高效液相色谱法测定SD大鼠体内多西紫杉醇血药浓度,并用3p97计算药动学参数。方法大鼠随机分为2组,分别尾静脉注射多西他赛注射液和多西紫杉醇泡囊于不同时间点采血,HPLC法测定其血浆药物浓度。HPLC法采用DiamonsilC18柱(250mm×46mm,5μm),流动相为甲醇/水(72/28,V/V),检测波长230nm,内标物为地西泮。结果在本色谱条件下多西紫杉醇与内标物及杂质峰分离良好,多西紫杉醇在血浆中1.0~20.0μg/ml浓度范围内线性关系良好(r=0.9982,n=6),平均回收率高,RSD小。结论该方法准确可靠、简单快速,可用于多西紫杉醇泡囊血浆内含量及药动学的测定,将多西紫杉醇制成泡囊,其AUC显著提高,清除率显著下降。 相似文献
136.
Mori T Hosokawa K Kinoshita Y Watanabe A Yamaguchi T Kuroboshi H Kato Y Yasuda J Fujita H Nakata Y Honjo H 《International journal of clinical oncology / Japan Society of Clinical Oncology》2007,12(3):205-211
Background It has been reported that a docetaxel-carboplatin combination as first-line chemotherapy for ovarian cancer showed a level
of progression-free survival similar to that of paclitaxel-carboplatin while reducing neurotoxicity and improving quality
of life. We investigated the recommended doses of docetaxel-carboplatin in Japanese patients with ovarian cancer and conducted
a comparative study of docetaxel-carboplatin versus paclitaxel-carboplatin.
Methods Thirty-nine patients with ovarian cancer were enrolled in this study and 38 patients were evaluated. We conducted a dose-escalation
study using a docetaxel dose of 70 mg/m2 and carboplatin AUC 5 and 6. In the comparative study, patients received either docetaxel 70 mg/m2 and carboplatin AUC 5 or paclitaxel 175 mg/m2 and carboplatin AUC 5. Progression-free survival, survival rate at 2 years, response rate, toxicity, and quality of life
were investigated.
Results In the dose-finding study, we determined the recommended doses as docetaxel 70 mg/m2 and carboplatin AUC 5. In the comparative study, the two arms showed similar progression-free survival. Grade 4 neutropenia
occurred more frequently in the docetaxel-carboplatin group (84.6%) than in the paclitaxel-carboplatin group (43.8%), while
sensory neurotoxicity was less frequent in the docetaxel-carboplatin group (53.8%) than in the paclitaxel-carboplatin (68.8%)
group. There were significant differences in the quality-of-life data in favor of docetaxel-carboplatin.
Conclusion We determined the recommended doses of docetaxel-carboplatin for Japanese patients with ovarian cancer to be docetaxel 70 mg/m2 and carboplatin AUC 5. In the comparative study, we suggest that the docetaxel-carboplatin combination is effective and well
tolerated as first-line chemotherapy for Japanese patients with ovarian cancer. 相似文献
137.
Kanai M Matsumoto S Nishimura T Shimada Y Watanabe G Kitano T Misawa A Ishiguro H Yoshikawa K Yanagihara K Teramukai S Mitsumori M Chiba T Sakai Y Fukushima M 《International journal of clinical oncology / Japan Society of Clinical Oncology》2007,12(3):224-227
Background The aim of this study was to evaluate the efficacy and safety of combination therapy with docetaxel and nedaplatin in advanced
esophageal cancer as a second-line regimen in an outpatient setting.
Methods Twenty-seven consecutive patients with advanced esophageal cancer who received docetaxel/nedaplatin combination therapy as
a second-line regimen were retrospectively evaluated. The combination therapy consisted of intravenous administration of docetaxel
30 mg/m2 and nedaplatin 40 mg/m2 every 2 weeks.
Results The patients received a median of 7.4 cycles of treatment (range, 2–25 cycles ). No complete response was observed, and 3
of the 27 patients (11%) achieved partial responses. The disease control rate (partial response + stable disease) was 52%.
The median survival time (MST) was 11.4 months. Severe hematological adverse events (grade 3–4) were: neutropenia (n = 10; 37%) and anemia (n = 5; 19%); there was neither febrile neutropenia nor grade 3-4 thrombocytopenia. Furthermore, no severe nonhematological
adverse events or treatment-related deaths were observed.
Conclusion Combination therapy of docetaxel with nedaplatin was safe and well tolerated; however, the development of more effective therapy
is warranted to improve the prognosis of esophageal cancer. 相似文献
138.
A systematic review of platinum and taxane resistance from bench to clinic: an inverse relationship 总被引:3,自引:0,他引:3
We undertook a systematic review of the pre-clinical and clinical literature for studies investigating the relationship between platinum and taxane resistance. Medline was searched for (1) cell models of acquired drug resistance reporting platinum and taxane sensitivities and (2) clinical trials of platinum or taxane salvage therapy in ovarian cancer. One hundred and thirty-seven models of acquired drug resistance were identified. 68.1% of cisplatin-resistant cells were sensitive to paclitaxel and 66.7% of paclitaxel-resistant cells were sensitive to cisplatin. A similar inverse pattern was observed for cisplatin vs. docetaxel, carboplatin vs. paclitaxel and carboplatin vs. docetaxel. These associations were independent of cancer type, agents used to develop resistance and reported mechanisms of resistance. Sixty-five eligible clinical trials of paclitaxel-based salvage after platinum therapy were identified. Studies of single agent paclitaxel in platinum-resistant ovarian cancer where patients had previously recieved paclitaxel had a pooled response rate of 35.3%, n=232, compared to 22% in paclitaxel na?ve patients n=1918 (p<0.01, Chi-squared). Suggesting that pre-treatment with paclitaxel may improve the response of salvage paclitaxel therapy. The response rate to paclitaxel/platinum combination regimens in platinum-sensitive ovarian cancer was 79.5%, n=88 compared to 49.4%, n=85 for paclitaxel combined with other agents (p<0.001, Chi-squared), suggesting a positive interaction between taxanes and platinum. Therefore, the inverse relationship between platinum and taxanes resistance seen in cell models is mirrored in the clinical response to these agents in ovarian cancer. An understanding of the cellular and molecular mechanisms responsible would be valuable in predicting response to salvage chemotherapy and may identify new therapeutic targets. 相似文献
139.
Lockhart AC Bukowski R Rothenberg ML Wang KK Cooper W Grover J Appleman L Mayer PR Shapiro M Zhu AX 《Cancer chemotherapy and pharmacology》2007,60(2):203-209
Purpose MAC-321 is a novel taxane that has demonstrated exceptional activity in human xenograft models when administered intravenously
and orally. Preclinical studies of MAC-321 have shown antitumor activity in MDR-expressing and paclitaxel-resistant tumors.
This phase I dose escalation study was performed to determine the safety, tolerability, and pharmacokinetic profile of orally
administered MAC-321 given once every 21 days. Preliminary antitumor activity of MAC-321 was also examined.
Methods Key eligibility criteria included adult subjects with refractory solid tumors or solid tumors for which conventional therapy
was unsuitable or did not exist, good performance status (ECOG ( 2), and adequate hematologic, hepatic, and renal functions.
Plasma pharmacokinetic (PK) sampling was performed during the first cycle of therapy.
Results Five dose levels of MAC-321 ranging from 25 to 75 mg/m2 were evaluated in 18 subjects (four women and 14 men). MAC-321 was well tolerated at the first three dose levels (25, 37,
50 mg/m2). Two subjects developed dose-limiting toxicities (DLTs) at 75 mg/m2; one subject with grade 3 and one subject with grade 4 neutropenia with fever. Three subjects treated at an intermediate
dose level of 60 mg/m2 had no DLTs. However, the study was terminated prior to completion of the maximal tolerated dose cohort after subjects treated
with intravenous MAC-321 in a concurrent study experienced life-threatening toxicities. Other common toxicities included grades
1–2 fatigue and grades 1–2 diarrhea. There was substantial interpatient variability in the PK parameters. MAC-321 was rapidly
absorbed with a mean C
max value of less than 1 h. Mean C
max and AUC values generally increased in a dose-related manner. The median terminal phase elimination half-life was 45 h (range
20–228 h). Disease stabilization was seen in four subjects with the following tumors: mesothelioma (14 cycles), chondrosarcoma
(12 cycles), small cell carcinoma (10 cycles), and prostate carcinoma (6 cycles).
Conclusions MAC-321 can be safely administered orally once every 21 days up to a dose of 60 mg/m2. The major DLT was neutropenic fever. Four subjects had disease stabilization. 相似文献
140.
Seiwert TY Cohen EE Haraf DJ Stenson K Blair EA Mauer A Dekker A Vokes EE 《Cancer investigation》2007,25(6):435-444
The purpose of this study was to determine the maximum tolerated dose (MTD) of docetaxel based induction and concomitant chemoradiotherapy (CRT) after using the FHX platform (5 = 5-FU, H = hydroxyurea, X = Radiation). Patients with Stage III/IV locally advanced HNSCC were enrolled. Induction chemotherapy (carboplatin/docetaxel) was followed by 5 cycles of concomitant docetaxel based CRT. No DLTs were observed in dose levels 1/2 for induction and CRT. Dose level 2 was expanded. The overall survival CR rate after CRT was 79 percent. Median overall (OS) has not been reached and 2-year OS is 80.7 percent. The recommended Phase II dose of docetaxel with FHX CRT is 25 mg/m2 and 35 mg/m2 in combination with carboplatin induction (AUC = 6). 相似文献