卡培他滨二线治疗非小细胞肺癌的剂量递增研究

目的 探讨卡培他滨(capecitabine,CAPE)联合多西紫杉醇(docetaxel,TXT)二线治疗非小细胞肺癌(NSCLC)时卡培他滨的最大耐受剂量(maximum-tolerated dose,MTD).方法 应用改良的Fibonacci法给予复治的NSCLC患者递增剂量的CAPE联合固定剂量TXT化疗,剂量Ⅰ(625 mg/m2,每天2次)和剂量Ⅱ(7 50 mg/m2,每天2次),两组1 8例患者共接受了67周期化疗.起始剂量为CAPE625 mg/m2,每天2次,d5～d18,TXT 30 mg/m2,d1,d8,每21天重复.如果没有剂量限制性毒性(dose limiting toxicity,DLT)出现,则升至下一剂量组,直至出现DLT.MTD定义为DLT出现的剂量水平的低一剂量.结果 主要的不良反应为粒细胞减少症、手足综合征、乏力和恶心.全组共5例发生8个DLT,剂量Ⅰ组1个(1例患者),剂量Ⅱ组7个(4例患者).由于在剂量Ⅱ组6例患者中4例出现了DLT,根据定义笔者确定剂量T为MTD.结论 此剂量递增试验的MTD是:卡培他滨1 250 mg/(m2·d)(625 mg/m2,每天2次)联合多西紫杉醇30mg/m2,d1,d8,每21天重复.复治NSCLC患者对此联合方案耐受性良好.     

多西紫杉醇联合米托蒽醌治疗晚期乳腺癌

目的:评定多的紫杉醇联合米托蒽醌治疗晚期乳腺癌临床疗效及不良反应。方法:52例病人均有病理学诊断及可评价客观指标。采用多西紫杉醇75mg/m~2d1,静脉滴注1小时,用多西紫杉醇前1天口服地塞米松10mg,连续3天。米托蒽酿14mg/m~2d1化疗。21～30天为1周期,2周期评价疗效。结果:52例病人可评价疗效和不良反应。CR 6例,PR 32例,NC 10例,PD 4例,有效率73.08％,不良反应主要为白细胞减少Ⅲ度占32.69％,Ⅳ度占25.00％;脱发Ⅱ度占44.23％,Ⅲ度占21.15％;腹泻Ⅱ度占32.69％,Ⅲ度占21.15％。结论:多西紫杉醇联合米托蒽醌治疗晚期乳腺癌有效率较高,不良反应可以耐受。     

多西紫杉醇联合长春瑞滨二线治疗晚期胃癌的临床观察

目的探讨多西紫杉醇联合长春瑞滨二线治疗晚期胃癌的客观疗效和安全性。方法既往一线应用不同化疗方案化疗失败的32例晚期胃癌患者,采用TN方案,即TXT 50 mg/m²,静脉滴注,d₁;NVB 25 mg/m²,静脉滴注,d₁;14天为一个周期。结果32例患者共完成134个周期化疗,有效率RR为43.8%（14/32）,中位TTP 5.0月,中位生存期9.0月,1年生存率为23.3%（7/30）。既往一线接受铂类和非铂类方案患者进行TN二线治疗的RR分别为50.0%和25.0%(P=0.412),中位生存期分别为9.0月和8.0月（P=0.174）,1年生存率分别为27.3%和12.5%（P=0.115）,差异无统计学意义。毒性反应主要为中性粒细胞减少（81.2%）,全组毒性反应均为可逆性。结论TN方案二线治疗晚期胃癌临床缓解率较高,不良反应可耐受;一线含铂与非含铂方案对其疗效基本没有影响。但由于观察数目较少,仍需扩大样本量进行进一步的研究。     

多西他赛联合洛铂治疗蒽环类耐药的晚期乳腺癌疗效分析

目的:观察多西他赛联合洛铂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:采用多西他赛联合洛铂方案治疗晚期乳腺癌患者42例。多西他赛75mg/m2静脉滴注第1天,洛铂30mg/m2静脉滴注第1天。每21天重复,至少应用2个周期。结果:42例患者中,CR、PR分别为4、19例,总有效率为54.8%(23/42),1年生存率为64.3%(27/42),主要不良反应为骨髓抑制。结论:多西他赛联合洛铂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。     

多西紫杉醇联合米托蒽醌治疗晚期乳腺癌的疗效观察

目的评定多西紫杉醇联合米托蒽醌治疗晚期乳腺癌临床疗效及不良反应.方法52例病人均有病理学诊断及可评价客观指标.采用多西紫杉醇75mg/m2d1,静脉滴注1小时,用多西紫杉醇前1天口服地塞米松10mg,连续3天.米托蒽醌14mg/m2d1化疗.21～30天为1周期,2周期评价疗效.结果52例病人可评价疗效和不良反应.CR6例,PR32例,NC10例,PD4例,有效率73.08%,不良反应主要为白细胞减少Ⅲ度占32.69%,Ⅳ度占25.00%;脱发Ⅱ度占44.23%,Ⅲ度占21.15%;腹泻Ⅱ度占32.69%,Ⅲ度占21.15%.结论多西紫杉醇联合米托恩醌治疗晚期乳腺癌有效率较高,不良反应可以耐受.     

多西他赛联合洛铂治疗蒽环类耐药的晚期乳腺癌疗效分析

目的：观察多西他赛联合洛铂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：采用多西他赛联合洛铂方案治疗晚期乳腺癌患者42例。多西他赛75mg/m2静脉滴注第1天,洛铂30mg/m2静脉滴注第1天。每21天重复,至少应用2个周期。结果：42例患者中,CR、PR分别为4、19例,总有效率为54.8%（23/42）,1年生存率为64.3%（27/42）,主要不良反应为骨髓抑制。结论：多西他赛联合洛铂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。     

周剂量紫杉醇联合方案治疗恶性肿瘤临床观察

目的 观察周剂量紫杉醇联合方案治疗恶性肿瘤的疗效及毒性。方法 对乳腺癌，肺癌等21例复治患者进行治疗：Paclitaxel 50-60mg/m^2静滴3小时，消化道肿瘤联合5－FU 400－500mg/m^2静滴，DDP30mg/m^2静滴，d1,8,15。28天为一周期。治疗2周期后评价疗效及毒性。结果 21例患者共化疗49周期，总有效率33．3％，其中CR0，PR33．3％（7／21），NC33．3％（7／21），PD23．8％（5／21），MR9．52％（2／21）。中位缓解时间7．2月，中位治疗到进展时间9．4月。主要毒性为白细胞下降，总发生率为76．19％，Ⅲ-Ⅳ度为19．04％；周围神经毒性：脱发，恶心，呕吐较常见。结论 周剂量紫杉醇联合方案治疗复治的恶性肿瘤有效率高，毒性反应比一次性给药低，病人可耐受。     

周剂量多西紫杉醇联合顺铂治疗晚期食管癌的临床观察

目的 观察分析周剂量多西紫杉醇(DTX)联合顺铂(DDP)方案治疗晚期食管癌的近期疗效和毒副反应.方法 29例Ⅲ、Ⅳ晚期食管癌,给予周剂量 DTX+DDP,即 DTX 30 mg/m2,d1.8.15,DDP 40 mg,d1-3,21 d为1周期,2个周期后按 WHO 标准评价疗效和毒副反应.结果 全组29例,均可评价疗效,总有效率55.2%,初治组(16例)有效率为62.5%,复治组(13例)有效率为46.2%.毒副反应主要表现为白细胞减少、胃肠道反应和脱发.结论 周剂量多西紫杉醇联合顺铂治疗晚期食管癌的近期疗效较高,毒副反应轻,值得进一步观察应用.     

单药周剂量多西紫杉醇治疗老年晚期恶性肿瘤的临床观察

目的 观察周剂量多西紫杉醇单药治疗老年晚期恶性肿瘤的疗效、毒副反应、临床受益反应.方法 多两他赛25 mg/m2静滴,d1,8,15,28 d为1周期,完成2周期后评价疗效.至少治疗2个周期.结果 68例均可评价疗效,总有效率为32.3%,其中非小细胞肺癌23例,有效率26.1%,胃癌14例,有效率28.5%,乳腺癌11例,有效率45.5%,前列腺癌12例,有效率41.7%,鼻咽癌8例,有效率25.0%,中位生存期为6.8个月,1年生存率及2年生存率分别为36.7%和22.0%.疾病相火症状显著改善,体力状态改善率60.3%,主要毒剐反应为脱发及骨髓抑制.无治疗相关性死亡.结论 周剂量多西紫杉醇单药治疗老年晚期恶性肿瘤有效率较高,毒副反应轻,耐受性好,并可以改善疾病相关症状,值得临床推广.     

周剂量多西紫杉醇联合顺铂、氟尿嘧啶二线治疗晚期胃癌32例

[目的]研究周剂量多西紫杉醇（TXT）联合顺铂（DDP）、氟尿嘧啶（5-Fu）持续滴注二线治疗晚期胃癌的疗效和不良反应。[方法]32例晚期胃癌患者接受DCF方案二线化疗：TXT30mg/m2,d1,8,15,DDP25mg/m2,d1～3,5-Fu500mg/m2持续静脉滴注,d1～5,28d为1个周期。至少完成2个周期后评价有效率、不良反应、疾病进展时间（TTP）和总生存时间（OS）。[结果]32例患者均可评价疗效,客观缓解率21.9%（7/32）,中位TTP及OS分别为2.7个月和7.6个月。主要不良反应为骨髓抑制、胃肠道反应和脱发。[结论]周剂量TXT联合DDP、5-Fu持续滴注二线治疗晚期胃癌疗效显著,不良反应可以耐受。     

洛铂联合阿霉素、异环磷酰胺化疗方案新辅助治疗骨肉瘤的剂量探索

目的 探讨洛铂（LBP）联合阿霉素（ADM）、异环磷酰胺（IFO）化疗方案新辅助治疗骨肉瘤的最大耐受量（MTD）,并观察其毒副反应。方法 LBP设定3个剂量水平,分别为45mg／m²、50mg／m²、55mg／m²,ADM和IFO剂量固定（ADM 60mg／m²、IFO 12g／m²）,观察到出现剂量限制性毒性（DLT）即终止试验,或至55mg／m²未出现DLT,试验亦终止。结果 共有6例患者完成了爬坡试验,当试验进行到第1个剂量组时,出现2例DLT,试验终止。从而确定联合化疗方案的MTD为LBP 45mg／m²、ADM 60mg／m²和IFO 12g／m²。主要不良反应为骨髓抑制,血小板减少的发生率为66.6％（4/6）,3级发生率为33.3％（2/6）;白细胞减少的发生率为83.3％（5/6）,未发生4级白细胞减少;中性粒细胞减少的发生率为83.3％（5/6）,4级发生率为33.3％（2/6）。所有患者经对症治疗后均好转,未影响继续治疗。结论 LBP联合ADM、IFO化疗方案新辅助治疗骨肉瘤的MTD为LBP 45mg／m²、ADM 60mg／m²和IFO12g／m²,毒副反应可耐受,建议以此为依据开展进一步临床研究。     

多西他赛联合洛铂新辅助化疗方案治疗三阴性乳腺癌的临床观察

目的 探讨多西他赛联合洛铂在三阴性乳腺癌（TNBC）新辅助化疗中的疗效和不良反应。方法30例TNBC患者应用多西他赛联合洛铂行新辅助化疗,具体方案为：多西他赛75mg／m²静滴,d1;洛铂30mg／m²静滴,d1;21天为1周期。按照WHO实体瘤客观疗效评价标准及术后病理组织学检测评价疗效,按照WHO急性及亚急性毒性标准评价毒副反应。结果8、17和5例患者分别完成2、4和6个周期的新辅助化疗,获CR 9例、PR 15例、SD 4例、PD 2例,RR为80.0％;术后病理组织学检测获病理学完全缓解6例。主要不良反应为骨髓抑制：1～2级白细胞减少17例,3～4级5例;1～2级血小板减少7例,3～4级2例;1～2级血红蛋白减少6例。非血液学毒性轻微。结论 多西他赛联合洛铂方案的疗效较好,毒副反应可耐受,是TNBC新辅助化疗方案的一个新选择。     

含多西他赛方案作为骨肉瘤二线化疗的疗效观察

目的 探讨含多西他赛方案二线治疗一线化疗失败的骨肉瘤肺转移患者的有效性和安全性。方法 收集2012年1月至2013年12月间我科收治的11例一线化疗失败的骨肉瘤肺转移患者,给予多西他赛（75 mg/m²,d₈）联合吉西他滨（675 mg/m²,d₁、d₈）／洛铂（30 mg/m²,d₂）方案二线化疗,21天为1周期,共化疗6个周期。采用RECIST标准10版评价疗效,NCI-CTC标准3.0版观察不良反应。结果 11例患者均完成化疗,可评价疗效。无完全缓解（CR）病例,部分缓解（PR）1例,疾病稳定（SD）4例,疾病进展（PD）6例;有效率（RR）为9.1％,疾病控制率（DCR）为45.5％。随访6～23个月, 3例死亡。中位无进展生存时间为10.5个月,中位生存时间为18.0个月,1年生存率为83.3％。主要不良反应为限制性骨髓抑制,化疗期间患者无明显肾功能异常及过敏反应,仅出现4级中性粒细胞及血小板减少1例。结论 含多西他赛方案二线治疗骨肉瘤肺转移,近期疗效满意,毒副反应可以耐受。     

洛铂联合多西他赛与多西他赛单药二线治疗晚期非小细胞肺癌的比较

目的 探讨洛铂联合多西他赛方案与单药多西他赛方案二线治疗非小细胞肺癌（NSCLC）的疗效和毒副反应。方法 将符合入组标准的42例晚期NSCLC患者分为观察组（n=15）和对照组（n=27）。观察组方案：多西他赛75mg／m2静滴,d1;洛铂30mg／m2静滴,d2,21～28天为1周期。对照组方案：多西他赛75mg／m2静滴,d1,21～28天为1周期。每组至少治疗3个周期,2个周期后评价疗效。结果 42例患者均可评价疗效。观察组的疾病控制率和有效率分别为73.3％（11／15）和26.7％（4／15）,对照组分别为63.0％（17／27）和22.2％（6／27）,两组比较差异均无统计学意义（P＞005）。观察组的平均生存时间为18.0个月,中位生存时间未达,较对照组的14.0个月长（P＜0.05）。观察组的中位无疾病进展时间为11.0个月,对照组为7.8个月,两组比较差异无统计学意义（P＞0.05）。在中性粒细胞减少、贫血和消化道反应的发生率方面,两组差异均无统计学意义（P＞0.05）;而观察组血小板减少的发生率高于对照组（P=0.047）。结论 洛铂联合多西他赛与单药多西他赛二线治疗NSCLC的近期疗效、生存期和毒副反应基本相似,需要进一步观察。     

A single-institute phase I/II trial combining nedaplatin dose escalation with a fixed dose of docetaxel for induction chemotherapy of oral squamous cell carcinoma

The purpose of this clinical trial was to assess the toxicity and efficacy of docetaxel plus nedaplatin induction chemotherapy in patients with locally advanced oral squamous cell carcinoma (OSCC). Twenty-one patients were enrolled in this phase I/II clinical study. The toxicities, response rates, and the maximum tolerated dose of nedaplatin that could be safely given preoperatively were assessed. Patients received escalating doses of nedaplatin (60, 70, 80, 90 mg/m²) combined with a fixed dose of docetaxel (60 mg/m²) on day one. Dose-limiting toxicity (DLT), grade 4 leukopenia lasting for two days or more, was seen in one patient at dose level 3; no other DLT was observed at any dose level. The overall response rate was 66.7%. The response rate was 100% at nedaplatin dose level 4, while that at dose level 1 was low (33.3%). Given these results, the recommended dose of nedaplatin in this regimen combined with fixed dose docetaxel (60 mg/m²) was determined to be 90 mg/m². Docetaxel 60 mg/m² plus nedaplatin 90 mg/m² induction chemotherapy can be recommended for patients with locally advanced oral squamous cell carcinoma. Based on these results, an early phase II clinical study using this dose level was conducted; docetaxel plus nedaplatin induction chemotherapy appears to be a useful regimen for the treatment of OSCC. A late phase II clinical study is warranted.     

Dose escalation study of docetaxel and nedaplatin in patients with relapsed or refractory squamous cell carcinoma of the esophagus pretreated using cisplatin, 5-fluorouracil, and radiation

Background Definitive chemoradiation with cisplatin (CDDP) and 5-fluorouracil (5FU) has been playing an important role in the treatment of esophageal cancer, but some patients are not curable or have recurrent lesions. However, few chemotherapeutic regimens are available for such patients. Docetaxel and nedaplatin are active for esophageal cancer. We conducted a dose-escalation study of docetaxel and nedaplatin as second line-chemotherapy after definitive chemoradiation in patients with relapsed or refractory squamous cell carcinoma of the esophagus after chemoradiation. Methods Nedaplatin was administered on day 1 and docetaxel was administered on days 1 and 15, every 4 weeks. Dose escalation was based on the dose-limiting toxicity (DLT) observed during the first cycle. Results Twelve patients were enrolled. At a docetaxel dose of 30 mg/m² and a nedaplatin dose of 80 mg/m², one grade 4 neutropenia occurred and caused one treatment break longer than 2 weeks, but there were few DLTs. At doses of 35 and 80 mg/m², respectively, two grade 4 neutropenias and one grade 2 thrombopenia occurred and caused three treatment breaks longer than 2 weeks. Therefore, the maximum tolerated dose was established at this dose level. Two grade 3 anorexias and one grade 3 nausea occurred, but other non-hematological toxicities were generally mild. Responses were seen in one-fourth of the 12 patients, including one complete remission. Conclusion The recommended doses of docetaxel and nedaplatin were 30 and 80 mg/m², respectively. This combination could be a potential second-line treatment for this target population.     

A dose escalation study of weekly docetaxel in patients with advanced solid tumors

Purpose: To determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) of weekly administration of docetaxel for three consecutive weeks every 4 weeks in patients with advanced solid tumors. Patients and methods: A total of 26 patients with malignant tumors refractory to conventional treatment were enrolled in this phase I study; their median age was 62 years. Of the 26 patients, 16 (62%) had previously received more than one chemotherapy regimen and 17 (65%) had previously received taxanes in a 3-week schedule. Docetaxel was administered after appropriate premedication at escalating doses (starting dose 30 mg/m²) as a 1-h i.v. infusion for three consecutive weeks in cycles of 4 weeks. Results: A total of 68 chemotherapy cycles were administered with a median of three cycles per patient (range one to six). The DLT was reached at 45 mg/m² per week and the dose-limiting events were grade 4 neutropenia, febrile neutropenia, and treatment delay due to incomplete hematologic recovery. The MTD was defined at a dose of 42 mg/m²/week. Grade 3/4 neutropenia occurred in seven patients (27%) (10% of cycles), and four patients (15%) developed febrile neutropenia. There were no deaths due to sepsis. Grade 2 peripheral neurotoxicity was observed in two patients (8%), grade 2 and 3 fatigue in 14 (54%), grade 2 edema in seven (27%), mild allergic reactions in two (8%) and lacrimation in three (12%). One (4%) complete response and eight (35%) partial responses (overall response rate 39%) were observed in 23 evaluable patients. Stable disease and progressive disease were observed in six patients (26%) and eight patients (35%), respectively. All responses were observed in patients with metastatic breast cancer, one of whom had progressed on paclitaxel-based and two of whom had progressed on docetaxel-based chemotherapy. Conclusions: The weekly administration of docetaxel for three consecutive weeks every 28 days is a feasible schedule with a favorable toxicity profile, and can be given on an outpatient basis. Moreover, this schedule of docetaxel administration seems to have an enhanced efficacy, especially in patients with advanced breast cancer who have failed front-line taxane-based chemotherapy. Received: 27 February 2000 / Accepted: 28 July 2000     

Doublet regimen of cisplatin plus docetaxel for second-line chemotherapy after prior therapy with cisplatin plus irinotecan for non-small cell lung cancer: a phase II study

Background To evaluate the safety and efficacy of second-line chemotherapy with docetaxel and cisplatin for non-small cell lung cancer (NSCLC), we performed a phase II study.Methods The subjects were 25 patients with NSCLC, 75 years or younger, without organ dysfunction (performance status [PS], 0 to 2) in whom treatment with cisplatin and irinotecan had been ineffective or had been followed by recurrence or relapse. Four weeks or more after the end of the previous therapy, 60mg/m² of cisplatin and 60mg/m² of docetaxel were administered at intervals of 3 weeks.Results Observed toxicities of grade 3 or 4 included anemia (24% of patients), leukocytopenia (48%), neutropenia (76%), thrombocytopenia (4%), hepatic dysfunction (8%), and electrolyte abnormalities (4%). However, no severe nonhematologic adverse reactions occurred. The overall response rate was 32% (95% confidence interval, 13.7–50.3). The median time to disease progression was 98 days, and the median survival time was 257 days.Conclusion Our results suggest that cisplatin and docetaxel can be used as second-line chemotherapy against NSCLC. But further, comparative, study of this combination should be performed in patients with good PS and organ function who have responded to prior platinum-based chemotherapy.