Methotrexate, vinblastine, doxorubicin and cisplatin combination regimen as salvage chemotherapy for patients with advanced or metastatic transitional cell carcinoma after failure of gemcitabine and cisplatin chemotherapy

We investigated the safety and efficacy of a methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) combination regimen as second-line chemotherapy for patients with advanced or metastatic transitional cell carcinoma who failed first-line gemcitabine and cisplatin (GC) chemotherapy. Thirty patients who had progressed or relapsed after GC chemotherapy as first-line treatment were enrolled in this study. The major toxicities were neutropaenia and thrombocytopaenia. A grade 3 or 4 neutropaenia occurred in 19 (63.3%) and a grade 3 or 4 thrombocytopaenia developed in nine patients (30.0%). There were no life-threatening complications during the study. The overall response was 30%. A complete response was achieved in two patients (6.7%) and a partial response in seven (23.3%). The overall disease control rate was 50%. Seven out of 16 patients who had responded previously to GC responded to M-VAC, while 2 out of 14 who had not responded to GC responded to M-VAC. The median response duration was 3.9 months and the median progression-free survival was 5.3 months. The median overall survival was 10.9 months. M-VAC showed encouraging efficacy and reversible toxicities in patients who had progressed after GC chemotherapy and, especially, M-VAC appears to be a reasonable option as a sequential treatment regimen in patients who responded previously to GC chemotherapy.     

Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) as neoadjuvant chemotherapy for patients with muscle-invasive transitional cell carcinoma of the bladder

BACKGROUND:

Meta‐analysis data demonstrate a 5% absolute survival benefit for neoadjuvant chemotherapy (NAC) using cisplatin‐based combination regimens in the radical treatment of muscle‐invasive bladder cancer (MIBC). However, there are no randomized, controlled trial data on the optimum regimen. Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) is a dose‐intense regimen that has the potential to minimize delays to definitive, potentially curative therapy. A retrospective analysis is presented of the efficacy and toxicity of AMVAC as NAC in patients with MIBC and its impact on the patient pathway.

METHODS:

Eighty consecutive patients with MIBC were treated with AMVAC as NAC by 2 UK multidisciplinary uro‐oncology teams. Three or 4 cycles of AMVAC (methotrexate 30 mg/m², vinblastine 3 mg/m², doxorubicin 30 mg/m², and cisplatin 70 mg/m²) were given at 2‐week intervals, with granulocyte colony‐stimulating factor support, prior to either radical surgery or radical radiotherapy.

RESULTS:

All planned cycles of chemotherapy were completed, without dose reduction or delay in 84% of patients. All 80 patients subsequently received their planned definitive therapy. Grade 3/4 toxicities were seen in 26% of the 42% of patients for whom toxicity data are available, including 12% grade 3/4 neutropenia. Pathological complete response to AMVAC was seen in 43% of 60 surgical patients. Objective radiological local response was seen in 83% of 57 evaluable patients. Two‐year disease‐free and overall survival were 65% and 77%, respectively.

CONCLUSIONS:

AMVAC is safe and appears to be a well‐tolerated and effective NAC regimen for MIBC. It minimizes delays to definitive treatment and produces excellent pathological and radiological response rates. It is an appropriate comparator for future randomized trials. Cancer 2012. © 2012 American Cancer Society.     

紫杉醇每周疗法联合顺铂治疗晚期非小细胞肺癌

目的:观察紫杉醇联合顺铂治疗晚期非小细胞肺癌(NSCLC)的临床疗效和毒副反应。方法:晚期NSCLC患者共32例,紫杉醇60mg/m2,第1、8、15天,静脉输注3小时。顺铂25mg/m2,静脉输注2小时,第2、3、4天,28天为1周期,至少治疗2周期。结果:全组32例中,CR2例,PR13例,NC14例,PD3例,有效率46.9%(15/32),毒性反应主要为骨髓抑制,脱发、神经毒性及恶心、呕吐等,患者均可耐受。结论:紫杉醇每周疗法联合顺铂治疗晚期NSCLC是一个疗效高,毒副作用可耐受的好方案。     

Biweekly paclitaxel and cisplatin in patients with advanced head and neck carcinoma

Background: Cisplatin is an active drug in head and neck cancer. Paclitaxel seems a promising drug. This article reports a phase II assessment of the combination of the two.Patients and methods: Twenty-three patients were treated with paclitaxel 90 mg/m² over three hours plus cisplatin 60 mg/m² every other week. Sixteen patients had locoregional disease and seven had metastatic disease. None of the patients had previously been treated with chemotherapy. Nine patients had had radiotherapy to the target lesions.Results: One patient was not evaluable for response. Partial responses were observed in 32% of evaluable patients. Toxicity included asthenia (56%), neutropenia, peripheral neuropathy, anemia and vomiting.Conclusions: The overall response rate observed in this study does not seem to justify the use of this chemotherapy regimen in the palliative setting.     

In vitro schedule-dependent interaction between paclitaxel and cisplatin in human carcinoma cell lines

 The schedule-dependent interaction of paclitaxel and cisplatin was studied in four human carcinoma cell lines: non-small cell lung cancer, A549; breast cancer, MCF7; ovarian cancer, PA1; and colon cancer, WiDr cells. The cells were exposed simultaneously to the drugs for 24 h and sequentially to paclitaxel first for 24 h followed by cisplatin for 24 h, or vice versa, and then incubated in drug-free medium for 4 and 3 days, respectively. Cell growth inhibition was then determined by the 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenyltetrazolium bromide (MTT) reduction assay. The effects of drug combinations at the IC₈₀ level were analyzed by the isobologram method. On simultaneous exposure to paclitaxel and cisplatin, additive and sub-additive (slight antagonistic) effects were observed in A549, MCF7, and PA1 cells, while sub-additive and protective (antagonistic) effects were observed in WiDr cells. On sequential exposure to paclitaxel first, followed by cisplatin, additive effects were observed in all cell lines. On sequential exposure to cisplatin first, followed by paclitaxel, additive effects were observed in PA1 cells, while additive, sub-additive, and protective effects were observed in A549, MCF7, and WiDr cells. These findings suggest that the interaction of paclitaxel and cisplatin is schedule- and cell line-dependent. The optimal schedule of this combination may be paclitaxel first followed by cisplatin. Received: 15 November 1994/Accepted: 21 June 1995     

紫杉醇联合顺铂治疗晚期乳腺癌临床观察

目的：观察紫杉醇联合顺铂（TP方案）治疗蒽环类耐药的复发转移性晚期乳腺癌的疗效与安全性。方法：从2005年6月-2008年6月以TP方案治疗蒽环类耐药的复发转移性晚期乳腺癌28例,紫杉醇135mg／m^2静滴,第1天;顺铂75mg／m^2静滴,第一天,21天为1周期,2个周期末评价近期疗效及安全性。结果：28例患者中CR1例（3．5％）,PR13例（46．4％）,SD8例（28．5％）,PD6例（21．4％）,有效率50％,不良反应主要是骨髓抑制,恶心、呕吐、脱发。结论：TP方案治疗蒽环类耐药的复发转移性晚期乳腺癌疗效可靠,不良反应可耐受,可作为蒽环类耐药的复发转移性晚期乳腺癌的化疗方案。     

紫杉醇联合顺铂治疗晚期非小细胞肺癌的临床观察

目的评价紫杉醇联合顺铂治疗非小细胞肺癌的临床疗效及毒性反应。方法紫杉醇150mg/m2静滴第1、8天,顺铂20mg静滴第1~5天,21天为1周期,治疗3个周期评价疗效。结果47例受治者,有效率为42.6%。毒副反应主要为恶心、呕吐、骨髓抑制。结论紫杉醇联合顺铂治疗非小细胞肺癌具有较好的疗效,毒副反应可以耐受。     

奈达铂联合紫杉醇和顺铂联合紫杉醇同步放化疗局部晚期鼻咽癌的临床随机对照实验

目的 通过临床随机对照实验观察奈达铂是否能够替代顺铂与紫杉醇联合同步放化疗局部晚期鼻咽癌,是否能够提高治疗的耐受性.方法 实验组(TN组)30例,采用紫杉醇135 mg/m2ivgtt d1+奈达铂10 mg/m2 ivgttd1诱导化疗,每3周为1个化疗周期,共2个疗程,以后行同样方案同期放化疗,仍然每3周为1个化疗...     

Phase I study of a biweekly schedule of a fixed dose of cisplatin with increasing doses of paclitaxel in patients with advanced oesophageal cancer.

We performed this dose-finding study with a fixed dose of cisplatin and increasing doses of paclitaxel given every 2 weeks to determine the maximum tolerable dose of this schedule. Sixty-four patients with advanced oesophageal cancer were treated with a cisplatin dose of 60 mg m(-2) and increasing doses of paclitaxel from 100 mg m(-2) up to 200 mg m(-2) both administered over 3 h for a maximum of six cycles in patients with stable disease or eight cycles in responding patients. Patients were retreated when the granulocytes were > 0.75 x 10(9) l(-1) and the platelets > 75 x 10(9) l(-1). The dose of paclitaxel could be increased to 200 mg m(-2) without encountering dose limiting haematological toxicity. At the dose levels 190 mg m(-2) and 200 mg m(-2) of paclitaxel cumulative sensory neurotoxicity became the dose-limiting toxicity. The dose intensity of paclitaxel calculated over six cycles rose from 50 mg m(-2) per week to 85 mg m(-2) per week. Only three episodes of granulocytopenic fever were encountered out of a total of 362 cycles of treatment. Of the 59 patients evaluable for response, 31 (52%) had a partial or complete response. In a biweekly schedule with a fixed dose of 60 mg m(-2) cisplatin it is possible to increase the dose of paclitaxel to 180 mg m(-2). At higher dose levels, neurotoxicity becomes the dose-limiting toxicity. The observed response rate warrants further investigation of this schedule.     

Weekly chemotherapy with docetaxel, gemcitabine and cisplatin in advanced transitional cell urothelial cancer: a phase II trial.

PURPOSE: To evaluate the efficacy and toxicity of a combination of weekly docetaxel, gemcitabine and cisplatin in advanced transitional cell carcinoma (TCC) of the bladder. PATIENTS AND METHODS: Thirty-five chemotherapy-na?ve (adjuvant and neoadjuvant chemotherapy was allowed) patients with advanced TCC received intravenous docetaxel 35 mg/m2, gemcitabine 800 mg/m2 and cisplatin 35 mg/m2, on days 1 and 8 every 3 weeks. Prophylactic granulocyte-colony stimulating factor was given from days 3 to 6 and days 10 to 15, anti-emetics were used routinely. RESULTS: Most (27) patients (77.1%) had a performance status of 0 to 1 and eight (22.9%) had received prior adjuvant or neoadjuvant cisplatin-based chemotherapy. In the intention-to-treat analysis, the objective response rate was 65.6% [23/35 patients, 95% confidence interval (CI) 47.8% to 80.9%]. Ten patients (28.5%) achieved a complete response (95% CI 14.6% to 46.3%) and 13 (37.1%) a partial response (95% CI 21.5% to 55.0%). Median survival time was 15.5 months, median duration of response was 10.2 months and median time to progression was 8.9 months. Ten patients (28.5%) developed grade 3/4 neutropenia, including five (14.3%) who experienced febrile neutropenia, which was successfully treated. Grade 3/4 anaemia and thrombocytopenia occurred in 20% and 25.7% of patients, respectively; four patients required platelet transfusions. There were no treatment-related deaths. CONCLUSIONS: Weekly docetaxel, gemcitabine plus cisplatin is a highly effective treatment for chemotherapy-na?ve advanced TCC, and causes only moderate toxicity. This regimen should be considered as a suitable option that deserves further prospective evaluation through randomised phase III trials.     

Phase I study of dose-escalated paclitaxel, ifosfamide, and cisplatin (PIC) combination chemotherapy in advanced solid tumours

Based on the already known in vitro synergy between paclitaxel (taxol), cisplatin and oxazophosphorine cytostatics and the broad spectrum of activity of the above drugs we sought to evaluate the paclitaxel (taxol)-ifosfamide-cisplatin (PIC) combination in the outpatient setting in individuals with a variety of advanced solid tumours. Cohorts of patients were entered into six successive dose levels (DLs) with drug doses ranging as follows: paclitaxel 135-215 mg m(-2) day 1 - (1 h infusion), ifosfamide 4.5-6.0 g m(-2) (total dose) - divided over days 1 and 2, and cisplatin 80-100 mg m(-2) (total) - divided over days 1 and 2. Granulocyte colony-stimulating factor was given from day 5 to 14. Forty-two patients were entered. Eighteen patients had 2-8 cycles of prior chemotherapy with no taxanes or ifosfamide (cisplatin was allowed). The regimen was tolerated with outpatient administration in 36/42 patients. Toxicities included: grade 4 neutropenia for < or = 5 days in 27% of cycles; 5 episodes of febrile neutropenia in three patients at DL-III, -V and -VI. Grade 3/4 thrombocytopenia and cumulative grade 3 anaemia were seen in 7% and 13% of cycles respectively. Three cases of severe grade 3 neuromotor/sensory neuropathy were recorded at DL-II, -III, and -V, all after cycle 3. The maximum tolerated dose was not formally reached at DL-V, but because of progressive anaemia and asthenia/fatigue, it was decided to test a new DL-VI with doses of paclitaxel 200 mg m(-2), ifosfamide 5.0 g m(-2) and cisplatin 100 mg m(-2); this appeared to be tolerable and is recommended for further phase II testing. The response rate was 47.5% (complete response + partial response: 20/42). The PIC regimen appears to be feasible and safe in the outpatient setting. Care should be paid to neurotoxicity. Phase II studies are starting in non-small-cell lung cancer, ovarian cancer and head and neck cancer at DL-VI.     

Nimotuzumab plus paclitaxel and cisplatin as the first line treatment for advanced esophageal squamous cell cancer: A single centre prospective phase II trial

Nimotuzumab (N) is a humanized anti‐epidermal growth factor receptor monoclonal antibody. This prospective, single‐armed, open label phase II study was conducted to evaluate the efficacy and safety of the combination of paclitaxel (T)/cisplatin (P) with nimotuzumab (N) as first‐line treatment in advanced esophageal squamous cell carcinoma (ESCC). Patients with pathologic confirmed unresectable locally advanced or metastatic ESCC were treated with the TPN regimen: nimotuzumab 200 mg weekly, paclitaxel 175 mg/m² on day 1 and cisplatin 30 mg/m² on days 1 and 2; repeat cycle every 3 weeks for six cycles. Radiotherapy was allowed to be admitted after four cycles of TPN treatment. The primary endpoint was the objective response rate (ORR). The secondary endpoint was the overall survival (OS), duration of disease control (DDC) and toxicities. From March 2011 to April 2013, a total of 59 patients were enrolled and 56 were eligible for the final analysis. Overall RR was 51.8% and disease control rate (DCR) (CR + PR + SD) was 92.9%. Local treatment (radiotherapy or surgery) followed by chemotherapy improved the duration of disease control for patients with metastatic disease and local‐regional advanced disease to 8.2 months and more than 23 months, respectively. The OS for patients with metastatic disease was 14.0 months (95% CI: 6.8–21.2 months). The most common G3/4 toxicities were neutropenia (46.4%), nausea (48.3%), alopecia (78.6%), anorexia (42.8%), vomiting (55.4%), arthralgia (62.5%) and anorexia (5%). Adding nimotuzumab to the standard TP regiment was safe, and well tolerated. The TPN regimen is an effective combination as the first‐line chemotherapy for the patients with advanced ESCC, and appears more active than current standard regimens.     

紫杉醇持续输注联合顺铂治疗晚期非小细胞肺癌

背景与目的：在许多国家肺癌的发病率和死亡率急剧增长，治疗肺癌的药物和方法不断涌现。本研究探讨紫杉醇静脉持续注射联合顺铂治疗晚期非小细胞肺癌的疗效和毒性。方法：61例晚期非小细胞肺癌患者被随机分为两组，治疗组（31例）方案：紫杉醇按总量150mg／m^2 48h静脉持续输注，第1～2天；顺铂按总量75mg／m^2分3d静点，即第3、4、5天。对照组（30例）方案：紫杉醇按总量150mg／m^2分2次静点，即第1、8天，每次持续3h，顺铂用法同治疗组。所有患者每周期21d，每个患者治疗3个周期以上。结果：治疗组与对照组的近期有效率分别为54．84％（17／31）、43．33％（13／30），中位治疗进展时间7．1个月、5．8个月，中位生存时间（MST）14．0个月、10．2个月，1年生存率67．74％（21／31）、33．33％（10／30），2年生存率22．58（7／31）％、13．33％（4／30），其中1年生存率治疗组显著高于对照组（P〈0．05），其余差异均无显著性（P〉0．05）。两组患者的不良反应有：骨髓抑制、恶心呕吐、脱发、外周神经毒性、肝功异常、肾功异常、静脉炎，两组发生率相当。结论：较传统用法，紫杉醇持续输注治疗晚期非小细胞肺癌能够提高有效率，显著改善生存情况。毒副反应无明显增加。     

紫杉醇联合顺铂与替吉奥联合顺铂治疗中晚期非小细胞肺癌的疗效对比研究

目的：对比分析中晚期肺癌治疗中紫杉醇与替吉奥分别联合顺铂的治疗方案的疗效差异。方法82例中晚期非小细胞肺癌中,以接受紫杉醇联合顺铂治疗的41例患者为对照组,接受替吉奥联合顺铂治疗的41例患者为观察组。对比两组近期疗效、远期疗效及不良反应发生率。结果经过4个疗程的治疗后,对照组治疗总有效率为19.51%,低于观察组的41.46%,差异有统计学意义（P﹤0.05）。随访结果显示,观察组中位生存期及中位无进展生存期分别为13.31个月及9.11个月,均高于对照组的10.83个月及8.28个月,差异有统计学意义（P﹤0.05）。此外,两组4个疗程治疗期间不良反应发生率比较,差异无统计学意义（P﹥0.05)。结论替吉奥联合顺铂治疗中晚期非小细胞肺癌相比紫杉醇联合顺铂治疗方案临床疗效及生存期更佳,且不良反应无明显增加。     

紫杉醇联合顺铂及5-氟尿嘧啶治疗进展期胃癌的临床观察

目的：观察紫杉醇（PTX）联合顺铂（CDDP）及5-氟尿嘧啶（5-Fu）方案（PCF方案）治疗进展期胃癌的近期疗效及不良反应.方法：选取病理检查证实的晚期胃癌患者36例,所有患者均有可评价病灶.化疗方案为：PTX 175mg/m2 ivgtt d1;CDDP 20mg/m 2,ivgtt d1-5;5-FU 750mg/m2,ivgtt24h d1-5.28天为1周期,所有患者至少接受2周期化疗.结果：36例患者均完成2个周期以上化疗,总有效率为61.1%,其中完全缓解（CR）3例,部分缓解（PR）19例,疾病稳定（NC）8例,疾病进展（PD）6例.生存期为5个月-24个月,中位生存期为11.5个月.主要不良反应为恶心、呕吐、腹泻和血白细胞、血红蛋白及血小板减少,其中Ⅲ度-Ⅳ度白细胞减少9人（25.0%）,其余大部分反应为Ⅰ度-Ⅱ度,无化疗相关死亡病例.结论：紫杉醇联合顺铂、5-氟尿嘧啶化疗方案治疗进展期胃癌疗效较好,不良反应可耐受.     

Supra-additive effect with concurrent paclitaxel and cisplatin in vulvar squamous cell carcinoma in vitro

The effect of concurrent paclitaxel and cisplatin was tested in vitro in 5 vulvar squamous cell carcinoma (SCC) cell lines (UM-SCV-1A, -2, -4 and -7 and UT-SCV-3). Chemosensitivity was tested using the 96-well plate clonogenic assay. Paclitaxel concentrations used varied between 0.4 and 1.6 nM, and cisplatin concentrations varied between 0.1 and 0.9 microg/ml. These drug concentrations are clinically achievable. Survival data were fitted to the LQ model, and the area under the curve (AUC) value was obtained with numerical integration. The type of interaction was determined by comparing the AUC ratio of the 2 drugs with the survival fraction (SF) of paclitaxel alone. With all cell lines tested the growth-inhibitory effect of simultaneous paclitaxel and cisplatin was at least additive. The effect of the tested combination on the UM-SCV-1A and UT-SCV-3 cell lines was clearly supra-additive with all paclitaxel concentrations tested, and the UM-SCV-4 and UM-SCV-7 cell lines exhibited a supra-additive effect with increasing paclitaxel concentrations. The degree of supra-additivity was dose-dependent in the UM-SCV-7 cell line with increasing synergy at higher paclitaxel doses. In the current study the combination of paclitaxel and cisplatin had a clear additive or supra-additive cytotoxic effect on the vulvar SCC cell lines, and it has been successfully used in other gynecologic malignancies; therefore concurrent paclitaxel and cisplatin also deserves further testing in clinical settings in advanced-stage vulvar carcinoma, which has a poor prognosis.     

奈达铂或顺铂联合紫杉醇治疗晚期食管癌的临床观察

目的评价并比较奈达铂/顺铂联合紫杉醇治疗晚期食管癌的疗效和不良反应。方法回顾性分析2006年至2011年收治的80例接受奈达铂联合紫杉醇（41例）或顺铂联合紫杉醇（39例）治疗的晚期食管癌患者,对比两种治疗方法的疗效及不良反应。结果奈达铂联合紫杉醇组（TN组）缓解率为26.8%;顺铂联合紫杉醇组（TP组）缓解率为23.1%,两组间差异无统计学意义（P=0.603）;TN组和TP组的中位疾病进展时间（time to progress,TTP）和中位总生存时间（overall survival,OS）分别为6个月和5个月、11个月和10个月,差异具有统计学意义（P=0.003,P=0.068）。常见的毒副反应主要是消化道毒性,血液学毒性和脱发。奈达铂组消化道毒性发生率及严重程度显著低于顺铂组,差异具有统计学意义（P=0.0001）。结论奈达铂联合紫杉醇治疗晚期食管癌患者其疗效和总生存与顺铂联合紫杉醇相似,但是在疾病无进展时间和消化道毒性发生率及严重程度上,奈达铂较顺铂有着显著的优势。     

Adjuvant chemotherapy with paclitaxel and cisplatin in lymph node-positive thoracic esophageal squamous cell carcinoma

Objective:No standard postoperative adjuvant chemotherapy has ever been established in node-positive esophageal squamous cell carcinoma (ESCC).This is a study to explore the effect of postoperative paclitaxel (PTX) and cisplatin (DDP) in lymph node-positive,completely resected thoracic ESCC patients.Methods:We conducted a prospective phase Ⅱ trial.Patents had pathologically node-positive thoracic ESCC with negative margins.Outcomes of disease-free survival (DFS) and overall survival (OS) were compared with a matched historical control cohort.The postoperative chemotherapy regimen consisted of 4 to 6 cycles of PTX 150 mg/m2 administered intravenously on d 1 followed by DDP 50 mg/m2 on d 2 every 14 d.Results:Forty-three patients were accrued from December 2007 to May 2012 at Cancer Hospital of Chinese Academy of Medical Sciences for adjuvant chemotherapy.The historical control group consisted of 80 patients who received complete resection but no adjuvant chemotherapy during the same period of time.Of the 43 patients with adjuvant chemotherapy,37 (86.0％) patients completed 4 to 6 cycles of chemotherapy.The 3-year DFS rates were 56.3％ in the adjuvant group and 34.6％ in the control group (P=0.006).The 3-year OS rates were 55.0％ in the adjuvant group and 37.5％ in the control group (P=0.013).Multivariate analysis revealed that postoperative chemotherapy was the significant predictor for improved OS (P=0.005).Conclusions:Biweekly adjuvant PTX and DDP might improve 3-year DFS and OS in lymph node-positive,curatively resected thoracic ESCC patients.These conclusions warrant further study in randomized phase Ⅲ clinical trials.     

紫杉醇联合顺铂及氟尿嘧啶治疗晚期胃癌

背景与目的:胃癌是我国最常见的恶性肿瘤,早期诊断率很低,多数患者确诊时已是晚期,失去手术根治机会,即使能够手术治疗,术后复发也很高,故药物治疗非常重要,但目前晚期胃癌的化疗效果不佳,尚缺乏公认的、规范高效的方案,因此开发新药、设计新的方案已成为晚期胃癌研究的热点。本研究探讨紫杉醇联合顺铂及氟尿嘧啶治疗晚期胃癌的客观疗效及安全性。方法:紫杉醇(pac litaxel)135 mg/m2,分第1、8天静滴,顺铂(DDP)20 mg/(m2.d)第1~3天静滴,氟尿嘧啶(5-FU)500 mg/m2第1天,静滴2 h,以后用5-FU 2 500 mg/m2泵内持续滴注,持续70 h,21~28 d为一周期,至少2个周期开始评价疗效,获CR、PR患者一个月后确认,不足2个周期的以观察毒性。结果:全组CR 2例,PR 22例,总有效率为51.1%,中位TTP为6.8个月;其中初治有13例,获CR 2例,PR 6例,总有效率为61.5%,中位TTP为7.1个月;复治患者为36例,可评价疗效的有34例,获CR 0例,PR 16例,总有效率为47.1%,中位TTP为6.5个月。而且获得CR和PR的病例,部分病例术后也获得病理组织完全缓解和部分缓解。毒副反应主要为血液学毒性及消化道反应,大部分为Ⅰ、Ⅱ度。结论:紫杉醇联合顺铂及氟尿嘧啶治疗晚期胃癌疗效肯定,特别对初治患者,毒副反应较轻,患者均能耐受,值得临床进一步扩大研究。     

Phase II trial of low-dose paclitaxel and cisplatin in patients with advanced gastric cancer

BACKGROUND: Paclitaxel has shown promising activity in gastric cancer and has synergism with cisplatin. This study was performed to evaluate the efficacy and toxicity of low-dose paclitaxel (145 mg/m(2)) plus cisplatin chemotherapy in metastatic or relapsed gastric cancer. METHODS: Chemotherapy-na?ve patients with metastatic or relapsed gastric cancer were enrolled. Paclitaxel 145 mg/m(2) was administered intravenously over 3 h, followed by cisplatin 60 mg/m(2) on Day 1 every 3 weeks in the outpatient setting. RESULTS: Of 39 patients enrolled, 17 (44%) had partial responses. Twelve (31%) had stable disease and eight (21%) progressive disease. Two patients (5%) were not evaluable because of early drop-out. The median time to progression was 4.7 months and the median overall survival was 12.1 months. The most common hematologic toxicity was anemia (41%). Grade 3/4 neutropenia and thrombocytopenia developed in 14 and 3%, respectively. The most common non-hematologic toxicities were peripheral neuropathy (43%) and emesis (43%). Grade 3/4 non-hematologic toxicities included emesis (11%), peripheral neuropathy (3%), diarrhea (3%) and hepatotoxicity (3%). CONCLUSIONS: Low-dose paclitaxel and cisplatin chemotherapy was active and well-tolerated in chemotherapy-na?ve gastric cancer patients. This regimen seems to have comparable efficacy to previously reported higher-dose paclitaxel plus cisplatin-containing regimens and fewer toxicities.