Phase II study of weekly paclitaxel,cisplatin, and 5-fluorouracil for advanced gastric cancer

Background  

Our previous phase I study provided evidence that weekly paclitaxel, cisplatin, and bolus 5-fluorouracil (weekly PCF) was effective and well tolerated in patients with advanced gastric cancer. This study was conducted to confirm the efficacy and toxicity of weekly PCF.     

Phase II trial of paclitaxel and cisplatin as neoadjuvant chemotherapy for locally advanced gastric cancer

Purpose

Paclitaxel–cisplatin (TC) combination is effective and well tolerated in patients with unresectable gastric cancer. We investigated the efficacy and safety of TC for locally advanced gastric cancers in a neoadjuvant setting.

Methods

Patients received 2–4 courses of paclitaxel (80 mg/m²) and cisplatin (25 mg/m²) on days 1, 8, and 15 in a 4-weekly schedule, followed by radical gastrectomy. Primary endpoint was the pathological response rate: percentage of tumors in which one-third or more parts were affected.

Results

All 52 patients enrolled were eligible. Thirty-six (69.7 %) patients completed two or more courses of chemotherapy. Forty-three patients (82.7 %) underwent surgery, 33 (63.5 %) had R0 resection, and there was no treatment-related death. The pathological response was 34.6 % (95 % CI 22.0–49.1) for all registered patients; the null hypothesis of tumor response ≤10 % was rejected (p < 0.0001). The 3-year overall survival was 41.5 % (95 % CI 27.4–55.0).

Conclusions

The neoadjuvant chemotherapy with TC was safe and effective for patients with locally advanced gastric cancer, and further study is needed to confirm the effectiveness of this regimen.     

紫杉醇联合顺铂新辅助化疗治疗胃癌的疗效观察

目的观察紫杉醇联合顺铂新辅助化疗对胃癌患者的疗效和安全性。方法选取2009年10月至2011年7月间南宫市人民医院收治的64例胃癌患者,采用随机数字表法分为治疗组与对照组,每组32例。治疗组患者术前采用紫杉醇联合顺铂化疗2个周期,化疗结束后进行手术治疗。对照组患者直接进行手术切除。对比两组患者根治性切除率、术后病理分期与术前临床分期差异、术后并发症发生率及术后2年生存率。结果两组患者均顺利完成手术,治疗组患者手术根治性切除率为87.5%,术后并发症发生率为12.5%,术后2年生存率为71.9%,对照组患者上述指标分别为65.6%、9.4%和46.9%,两组患者根治性切除率和术后2年生存率比较,差异均有统计学意义(均P<0.05),而术后并发症发生率比较,差异无统计学意义(P>0.05)。治疗组中有10例患者术后病理分期低于术前临床分期,对照组患者中有2例,两组比较,差异有统计学意义(P<0.05)。结论术前紫杉醇联合顺铂新辅助化疗能提高胃癌根治性切除率,降低病理分期,提高患者生存率,且安全性较高,值得临床推广应用。     

紫杉醇联合顺铂、5-氟尿嘧啶(TPF方案)新辅助化疗治疗晚期鼻咽癌的临床分析

目的:评价紫杉醇联合顺铂(DDP)、5-氟尿嘧啶(5-FU)(TPF方案)治疗晚期鼻咽癌的疗效和不良反应.方法:Ⅲ-Ⅳa 期鼻咽癌患者98例随机分为紫杉醇+顺铂+5-氟尿嘧啶新辅助化疗联合同期放化疗(治疗组)及以5-氟尿嘧啶+顺铂组成的同期放化疗组(对照组).新辅助化疗药用量:紫杉醇 135mg/m2,d1,顺铂20mg/m2,d1-5,5-氟尿嘧啶750mg/ m2,d1-5,每21天重复,治疗组所有病人均接受两个疗程TPF方案新辅助化疗.第2程新辅助化疗后14天即开始放疗.两组同期放疗相同.放疗采取 6MV X线常规照射,鼻咽部总剂量约 DT 70Gy/49天,颈部预防剂量约 DT 50-55Gy/35-42天,治疗剂量约 60-70 Gy/42-49天.比较两组疗效及不良反应.结果:治疗组鼻咽及颈部肿瘤消失的平均剂量小于对照组(P＜0.05) ;两组肿瘤临床全消率分别为87.8%与77.6%(P＜0.01).不良反应主要为粒细胞下降、脱发、口腔黏膜反应及胃肠道反应,均能耐受.结论:紫杉醇联合顺铂、5-氟尿嘧啶新辅助化疗治疗晚期鼻咽癌可提高肿瘤消失率,是治疗晚期鼻咽癌有效安全的方案.     

Early postoperative intraperitoneal chemotherapy with mitomycin C, 5-fluorouracil and cisplatin for advanced gastric cancer

OBJECTIVE: The long-term survival of patients who undergo surgery for stage IV gastric cancer is poor, due to metastatic spread of the tumor. Intraperitoneal chemotherapy (IPT) as a possible treatment for peritoneal dissemination has been investigated in a number of different tumors. The aim of this study was to investigate the toxicity and impact of early postoperative IPT on the survival of patients with advanced gastric cancer. METHODS: Between 1993 and 1997, a total of 91 patients with stage IV gastric cancer who underwent potentially curative or palliative resection received intraperitoneal mitomycin C before closure of the abdominal wound. 5-Fluorouracil and cisplatin were administered intraperitoneally on postoperative days 1-4, and this was repeated at 4-week intervals. RESULTS: All patients received a median of 3 IPT perfusions. There were 24 (26.4%) postoperative complications and 1 (1.1%) mortality. The most frequent hematologic toxicity (grade 3-4) was leukopenia. The major nonhematologic toxicities (grade 3-4) were emesis and nephrotoxicity. After a median follow-up period of 26 months, 14 patients remain alive without evidence of recurrence, whereas 75 patients died due to recurrence or progression of disease. The median survival period for all 91 patients was 15.4 months. When survival according to the residual tumor was analyzed, median survival was 36.0 months in the R0 (curative resection) group, 20.6 months in the R1 group (margins of resected specimens showing microscopic residual tumor or diameter of each residual tumor less than 3 mm) and 9.0 months in the R2 group (macroscopic residual tumor larger than 3 mm) (p < 0.001). CONCLUSIONS: IPT was found to be safe, and it appears to improve the prognosis in patients with minimal residual tumors. However, complete cytoreductive surgery is mandatory for achieving the beneficial effect of IPT.     

替吉奥联合顺铂与5-氟尿嘧啶联合顺铂治疗晚期胃癌对照研究的Meta分析

目的:比较替吉奥联合顺铂方案(SP方案)和5-氟尿嘧啶联合顺铂方案(FP方案)一线治疗晚期胃癌的疗效及安全性。方法:计算机检索Pubmed、EMBASE、Cochrane Library、ASCO会议摘要、中国期刊全文数据库、中国生物医学文献数据库、中文科技期刊全文数据库等,同时追查纳入文献的参考文献,纳入SP方案对比FP方案治疗晚期胃癌的随机对照试验(RCT)。根据Cochrane Handbook 5.0的质量评价标准,用RevMan 5.0软件进行统计学分析。结果:纳入4项RCT,1 263例患者,Meta分析结果显示,采用SP方案与FP方案治疗后疗效相当(OR=1.58,95%CI:0.76～3.29,P=0.22),但可以降低3/4级血小板减少(OR=0.58,95%CI:0.40～0.85,P=0.004)及恶心呕吐(OR=0.70,95%CI:0.52～0.95,P=0.02)发生率;亚组分析(中国人群),纳入3项RCT,234例患者,Meta分析结果显示,与FP方案相比,SP方案可提高患者有效率(OR=2.39,95%CI:1.30～4.38,P=0.005),但不能降低不良反应发生率,差异均无统计学意义。结论:SP方案与FP方案在有效率方面疗效相当,但可以增加安全性,不良反应发生率与FP方案类似,但由于研究例数较少,该结论尚待进一步扩大样本量进行评估。     

Single-agent paclitaxel in advanced anal cancer after failure of cisplatin and 5-fluorouracil chemotherapy

Squamous cell cancer of the anal canal (anal cancer) is a rare disease but with worldwide increasing incidence. While combined therapy of 5-fluorouracil (5-FU), mitomycin, and radiation is the treatment of choice for locoregional anal cancer, the treatment of metastatic disease is less established. 5-FU and cisplatin combination has been adopted as the first-line treatment of choice for metastatic disease based on several phase II studies. However, no standard therapy has been established for stage IV anal cancer after the failure of this combination. Paclitaxel, a microtubule-stabilizing chemotherapeutic agent, has established clinical activity in squamous cell cancer of the head and neck. One prior report described the activity of paclitaxel in five patients with anal cancer. In this report, we describe our experience using this agent in seven patients suffering from metastatic anal cancer with prior progression on cisplatin and 5-FU. Four patients had an objective response and one patient experienced stable disease. Our results confirm activity of weekly-paclitaxel in patients with 5-FU and cisplatin-resistant metastatic anal cancer.     

Evaluation of TS-1 combined with cisplatin for neoadjuvant chemotherapy in patients with advanced gastric cancer

We performed a critical evaluation of neoadjuvant chemotherapy (NAC) with TS-1 and cisplatin (CDDP) for advanced gastric cancer patients. Since October 2000, 37 patients with far advanced or non-curative resectable gastric cancer received NAC, together with TS-1 and CDDP after informed consent was obtained. TS-1 (80 mg/m2/day) was administrated for 21 consecutive days followed by 14 days rest as one course, and CDDP (50 mg/m2) was infused over 2 hours on day 8. After at least 2 courses of treatment, the patients underwent gastrectomy with lymphadenectomy. The median number of courses administered was 3 (range 2-7), and 6 cases were treated on an outpatient basis only. The overall response rate was 62.2% (no CR, but 23 PR), and the individual response rates were 67.6% for the primary lesion, 90.5% for lymph node metastasis including para-aortic region, 50.0% for liver metastasis and 14.3% for peritoneal dissemination, respectively. Toxicities were generally mild, no treatment-related death and no serious adverse reactions were observed. There were only 2 grade 4 anemia (5.4%), and leucopenia, neutropenia, anemia, thrombocytopenia of grade 3 were observed in one (2.7%), 3 (8.1%), 6 (16.2%), and 2 (5.4%) patients respectively at hematological toxicity. Appetite loss and diarrhea of grade 3 were observed in only one (2.7%) patient at nonhematological toxicity. Twenty-four cases had undergone surgical treatment, and resection was performed in all cases. Seventeen of the 24 (70.8%) patients underwent curative resection. There was no major morbidity following surgery. The patients were favorable both for operation time (229 min) and bleeding volume (365 ml). The mean duration of hospitalization after surgery was 23.5 days and the only complications were one leakage, ileus and 2 pancreatitis. Two-year survival rate was 46.8% and MST was 523 days. In conclusion, a combination of TS-1 and CDDP for NAC appears to be an effective treatment modality for far advanced gastric cancer patients in view of toxicities, antitumor effects and QOL of the patients.     

联合化疗方案治疗晚期胃癌的临床疗效分析和安全性评估

目的探讨联合化疗方案PDF即紫杉醇（PTX）＋顺铂（DDP）＋5-氟尿嘧啶（5-Fu）治疗晚期胃癌的临床疗效情况和安全性。方法入选2008年1月至2010年12月期间晚期胃癌患者80例,随机分为治疗组（40例）和对照组（40例）。对照组患者采用5-Fu治疗。治疗组患者采用PTX（135mg／m^2）静脉滴注3h,第1天;DDP（25mg／m^2）静脉滴注,第1—3天;5-Fu（750mg／m^2）静脉滴注,第1～5天,28天为1个化疗周期。2个周期后分析两组患者的疗效和不良反应。结果治疗组患者中,完全缓解（CR）8例,部分缓解（PR）10例,稳定（SD）15例,进展（PD）7例,临床有效率为45．0％,临床受益率为82．5％,明显高于对照组。治疗组患者的不良反应主要是骨髓抑制和消化道反应,症状较轻,不良反应明显低于对照组。结论采用联合化疗方案治疗晚期胃癌可提高疗效,且不良反应较轻,值得临床上推广。     

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.     

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.     

Paclitaxel, 5-fluorouracil, and cisplatin combination chemotherapy for the treatment of advanced gastric carcinoma

BACKGROUND: Although the clinical efficacy of paclitaxel in the treatment of gastric carcinoma has not been clearly defined, recent reports have suggested a possible role in the treatment of upper gastrointestinal carcinomas in vitro and in vivo. In this study, the authors evaluated the efficacy and toxicity of a combination chemotherapy that included paclitaxel, 5-fluorouracil (5-FU), and cisplatin in the treatment of patients with advanced gastric carcinoma. METHODS: Forty-one gastric carcinoma patients with metastatic disease, unresectable advanced disease, or relapsed disease were treated with the following regimen, administered every 28 days: paclitaxel 175 mg/m2 by 3-hour intravenous (i.v.) infusion on Day 1, 5-FU 750 mg/m2 by 24-hour continuous i.v. infusion on Days 1-5, and cisplatin 20 mg/m2 by 2-hour i.v. infusion on Days 1-5. Twenty-six patients had measurable disease, and 15 had evaluable disease. All patients were assessable for toxicity. RESULTS: Twenty-one of the 41 patients (51%; 95% confidence interval [CI], 36.5-65.7%) demonstrated an objective response, including 4 complete responses (10%; 95% CI, 3.9-22.5%). Sixty-five percent of the patients with measurable disease (17 of 26; 95% CI, 58-92.5%) and 27% of the patients with evaluable disease (4 of 15: 95% CI, 11.1-52.3%) achieved a complete response or a partial response. The median response duration was 17 weeks (range, 4-90 weeks), and the median survival duration for all patients was 26 weeks (range, 8 to 118+ weeks). The major toxicity of this treatment was myelosuppression with neutropenia of World Health Organization Grade 3 and 4 in 24% and 10% of the patients, respectively. Nonhematologic toxicity included mucositis, nausea/vomiting, diarrhea, neurotoxicity, and alopecia. Fluid retention occurred in two patients, and one patient had an anaphylatic reaction. Dose reduction was necessary for one patient, because Grade 4 neutropenia and mucositis occurred. CONCLUSIONS: Paclitaxel, 5-FU, and cisplatin was an active combination regimen in the treatment of advanced gastric carcinoma. The toxicity of this regimen was tolerable. Based on these findings, this combination regimen could be an attractive treatment in the preoperative setting.     

Bolus and infusional 5-fluorouracil combined with cisplatin in advanced gastric cancer

5-Fluorouracil (5-FU) is the main drug used in the treatment of advanced gastric cancer. Combination chemotherapy is not always superior to 5-FU alone, especially when biomodulators are also administered. In an attempt to exploit all the cytotoxic mechanisms of 5-FU, we carried out a pilot study with a double route of administration of 5-FU (intravenous bolus and continuous infusion) and a multiple modulation of 5-FU by methotrexate (MTX), 6S-leucovorin (6S-LV) and cisplatin (CDDP). A group of 30 patients affected by advanced gastric cancer was treated with MTX 50 mg/m2 and 5-FU 400 mg/m2 as an i.v. bolus on day 1, followed by a 5 day i. v. continuous infusion of 5-FU 600 mg/m2/day and 6S-LV 100 mg/m2/day; on day 3 CDDP 100 mg/m2 was also administered. The regimen was repeated every 4 weeks. Six partial responses (20+/-14. 3%), 12 stable diseases (40+/-17.5%) and 12 progression (40+/-17.5%) were observed in an intent-to-treat analysis. Median survival was 7 months. All responding patients had performance status 0-1. Grade 3-4 toxicity was mainly gastrointestinal, but grade 3-4 anemia and leucopenia were also recorded. The schedule has low activity. The use of different modulators and way of administration of 5-FU does not provide advantages in advanced gastric cancer.     

Validity of neoadjuvant chemotherapy with docetaxel,cisplatin, and S-1 for resectable locally advanced gastric cancer

Gastrectomy with D2 lymphadenectomy plus postoperative chemotherapy is the standard treatment for resectable locally advanced gastric cancer in Japan. However, the prognosis of patients with serosa-positive tumors remains unsatisfactory because of peritoneal recurrence. This study aimed to investigate the validity of neoadjuvant therapy with docetaxel, cisplatin, and S-1 (DCS) in patients with locally advanced gastric cancer. Thirty patients with locally advanced gastric cancer underwent neoadjuvant DCS therapy at Dokkyo Medical University Hospital between June 2013 and October 2015. Gastrectomy and D2 lymphadenectomy were performed after two cycles of preoperative DCS therapy. The clinical responses of the primary gastric tumors based on endoscopic findings were partial response in 17 patients (57%) and stable disease in 13 patients (43%). Analysis of pathological response in the primary gastric lesions showed grade 1a in five patients (17%), grade 1b in nine patients (30%), grade 2 in 11 patients (37%), and grade 3 in five patients (17%). Twenty-four patients (80%) remained alive after a median follow-up period of 31 months. The 2- and 3-year overall survival rates in all patients were 89 and 70%, respectively. The 2-year overall survival rate in pathological responders (grade 1b-3) was 96%, compared with 50% in pathological non-responders (grade 1a) (P = 0.00187). Pathological responders had a significantly higher survival rate than non-responders. These results indicate that neoadjuvant DCS therapy may improve the prognosis in patients with serosa-positive locally advanced gastric cancer.     

Effective use of combination chemotherapy with paclitaxel and 5-fluorouracil in a case of non-resectable advanced gastric cancer

The patient was a 67-year-old man who had gastric cancer located in the posterior wall of the stomach and who underwent surgery on June 27, 2001. The operative finding was carcinomatous peritonitis in which the primary lesion was considered to be surgically unresectable. Therefore, only a probe laparotomy was performed. Under full informed consent, we performed combination chemotherapy with paclitaxel and 5-fluorouracil, 5-fluorouracil (600 mg/m2/day) was infused continuously for 120-hours (day 1-5) on administration and paclitaxel (60 mg/m2) was infused for 1.5 hours after premedication at day 8, 15 and 22 on an outpatient basis. After 2 courses of the chemotherapy, the tumor markers were reduced remarkably, ascites had completely disappeared, and abdominal lymph nodes had decreased. No serious adverse event was observed and the patient maintained good QOL throughout the treatment.     

Gemcitabine versus combined chemotherapy with 5-fluorouracil and cisplatin in advanced pancreatic cancer

Gemcitabine hydrochloride (GEM) is a first-line therapeutic agent for advanced pancreatic cancer, but there is no established second-line treatment after GEM failure. We assessed the clinical benefit of systemic combined chemotherapy with 5-fluorouracil and cisplatin (FP therapy) in 19 patients compared with GEM in 32 patients, respectively. Tumor response rates were 10.5% and 15.6% for FP therapy and GEM, respectively. The median survival time in the FP therapy and GEM was 137 days and 241 days, respectively. Although clinical benefit was similar in both types of therapy, median survival time was more favorable for GEM, especially for Stage IVb. Nausea and vomiting were the most commonly observed toxicity in the FP therapy group. Our data indicate that FP therapy is not considered to be a useful second-line agent in patients with GEM pretreated pancreatic cancer.     

多西他赛联合顺铂和氟尿嘧啶治疗晚期胃癌疗效观察

目的观察多西他赛联合顺铂、氟尿嘧啶(DCF方案)治疗晚期胃癌的疗效和不良反应。方法采用DCF方案治疗33例晚期胃癌患者。多西他赛75 mg/m2,d1;顺铂75 mg/m2,d1;氟尿嘧啶750 mg/m2,持续静脉滴注,d1~5,3周1个周期,至少2个周期。结果33例晚期胃癌中,完全缓解(CR)0例,部分缓解(PR)18例(54.5%),稳定(SD)8例(24.2%),进展(PD)7例(21.2%)。中位肿瘤进展时间为6.1个月(3.5~11.5个月),中位总生存期为11.2个月(6.0~14.5个月)。最常见的不良反应为骨髓抑制、消化道反应及可逆性体液潴留,不良反应多为Ⅰ~Ⅱ度,无Ⅳ度不良反应发生。骨髓抑制以白细胞减少为特点,血小板减少及贫血较轻。消化道反应主要表现为恶心呕吐、腹泻、便秘,无Ⅳ度腹泻发生。无治疗相关性死亡。结论DCF方案是治疗晚期胃癌安全有效的化疗方案。     

奥沙利铂联合5-氟尿嘧啶和醛氢叶酸钙时辰治疗晚期胃癌的初步临床研究

目的观察奥沙利铂(L-OHP)联合5-氟尿嘧啶(5-Fu)、醛氢叶酸钙(FA)方案(FFL方案)时辰输注法治疗晚期胃癌的疗效和不良反应。方法FFL方案时辰输注法治疗26例晚期胃癌患者,L-OHP 25 mg.m-2.d-1,5-Fu 600 mg.m-2.d-1,FA 300 mg.m-2.d-1,多通道程控时辰输液泵连续给药4 d,每14 d为1个周期,至少用2个周期。结果26例晚期胃癌患者中,完全缓解(CR)2例(7.7%),部分缓解(PR)13例(50.0%),稳定(SD)6例(23.1%),进展(PD)5例(19.2%),总有效率为57.7%。在共80个周期的化疗中,最常见的不良反应为血液学毒性、胃肠道毒性、外周神经毒性,但均以Ⅰ度为主,Ⅲ度中性粒细胞减少发生2例次,血小板减少、呕吐和口腔黏膜炎分别发生1例次,未出现Ⅳ度不良反应。中位缓解时间为3.5个月,中位肿瘤进展时间为4.5个月,全组患者中位生存期为8个月。结论FFL方案时辰输注法是治疗晚期胃癌安全有效的化疗方案。     

Sequential chemotherapy with low-dose methotrexate and 5-fluorouracil in advanced gastric cancer

Sequential chemotherapy with low-dose methotrexate (30 mg/body) and 5-FU (750 mg/m2) was undertaken in 16 patients with advanced gastric cancer. Following the chemotherapy, leucovorin (30 mg/body) was injected intravenously. These treatment were repeated weekly for two to eight weeks. Out of 16 patients, two partial remissions and two minor responses were obtained. The overall response rate was 12.5%. There were no cases of renal or hematologic toxicity. The only adverse effect was nausea. We concluded therefore, that sequential chemotherapy with low-dose methotrexate and 5-FU is a useful method for advanced gastric cancer.