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.     

紫杉醇联合氟尿嘧啶和顺铂方案治疗晚期胃癌

目的：观察紫杉醇联合氟尿嘧啶及顺铂（PFC）方案治疗国人晚期胃癌的临床疗效和毒副反应.方法：晚期胃癌患者25例,给予紫杉醇（PTX）50mg/m^2,静滴3小时,第1、8、15天给药;氟尿嘧啶（5-FU）750mg/m^2,持续静脉输注24小时,第1～5天;顺铂（CDDP）20mg/m^2,静脉滴注,第1～5天,28天为1周期.分别化疗2～6周期后按WHO标准评价疗效和毒副反应.结果：全组25例均可评价疗效,获得CR 2例,PR 11例,SD 7例,PD 5例,近期客观有效率52.0%,中位TTP为6.5月.主要毒副反应为骨髓抑制、恶心呕吐和脱发.结论：PFC方案治疗国人晚期胃癌疗效较高,毒副反应轻,多数患者耐受良好,值得推广应用.     

Phase II study of 5-fluorouracil, pirarubicin and low-dose consecutive administration of cisplatin for advanced and recurrent gastric cancer

BACKGROUND: The FAP regimen was modified and low-dose consecutive daily administration of cisplatin (CDDP) and continuous infusion of 5-fluorouracil (5-FU) and pirarubicin were employed to reduce the toxicity and achieve synergy. Patients with advanced and recurrent gastric cancer were treated with this regimen as early phase II trial and its efficacy and toxicity were assessed. METHODS: Twenty-nine patients with advanced or recurrent gastric cancer were treated with intravenous 5-FU, 360 mg/m2, continuous infusion, on days 1-5 and 8-12, CDDP, 10 mg/body, drip infusion, on days 1-5 and 8-12 and pirarubicin, 20 mg/body, on days 1 and 8, which was repeated every 4 weeks. RESULTS: One complete (CR) and 10 partial (PR) responses were observed. Eleven patients showed no change (NC) and seven had progressive disease (PD). The overall response rate (CR and PR) was 37.9%. The response rates of lymph node metastatic lesions and primary gastric lesions were 47 and 44%, respectively. The major toxicity was bone marrow suppression, which was well tolerated. Grade 3/4 nausea/vomiting did not occur. The median survival of all patients was 30 weeks, that of those who responded was 48 weeks and that of those showing NC or PD was 24 weeks. CONCLUSIONS: This modified FAP regimen was considered useful with a moderate response and less severe toxicity, but further investigation is necessary.      

A phase II trial of low dose administration of 5-fluorouracil and cisplatin in patients with advanced and recurrent gastric cancer.

The clinical efficacy of chemotherapy for patients with advanced gastric cancer has not been established. We investigated in a phase II study the combination chemotherapy of low dose 5-fluorouracil (5-FU) and cisplatin (low dose FP) to evaluate its clinical efficacy in terms of response, quality of life and survival in 43 gastric cancer patients including 29 advanced and 14 recurrent cases. The administration of 5-FU was done by continuous intravenous infusion for 28 consecutive days with a dose of 250 mg/m2, while the administration of cisplatin was done by 1-h intravenous drip-infusion for 5 consecutive days and 2-day intervals per week with a dose of 3.5 mg/m2, that was repeated for 4 weeks in one cycle. The response rate in advanced cases was 48.3%, evaluated in 14 cases of partial response (PR), whereas its response rate in recurrent cases was 35.7%, evaluated in 5 cases of PR. The most effective lesions for low dose FP chemotherapy were primary lesion and lymph node metastasis. The quality of life assessed by performance status and oral intake was improved in 13.8% and 37.9% of advanced cases, and 21.4% and 28.6% of recurrent cases, respectively, as compared to those of pretreatment. The median survival time and 1-year survival rate were 6 months, 21.6% in advanced cases and 10 months, 28.8% in recurrent cases, respectively. The major adverse effect was observed in gastrointestinal toxicity and leukopenia, and the all toxicities were less than grade 2, that were controllable during the treatment. These results indicated that the combination chemotherapy of low dose administration of 5-FU and cisplatin might have therapeutic efficacy in tumor response and offer improvement in quality of life in patients with advanced and recurrent gastric cancer.     

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。     

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.     

Cisplatin and 5-fluorouracil in advanced and recurrent cervical cancer

Nineteen consecutive patients with advanced or recurrent cervical cancer were treated with cisplatin 20 mg/m2 plus 5-fluorouracil 200 mg/m2 on days 1-5 every 3 weeks. Toxicity was acceptable and manageable, with most patients treated on an outpatient basis. The most important side effect was dose-cumulative neurotoxicity. In 18 evaluable patients a 61% objective response rate (1 complete and 10 partial) was achieved. In recurrent disease the regimen was effective both in irradiated lesions and in non-irradiated ones. Two out of five patients not previously treated with radiotherapy and/or chemotherapy responded to the treatment but tumor regression was insufficient for the disease to be controlled radically by subsequent surgery or radiotherapy. The median duration of response was 11 months (3-23) and the actuarial survival rate after 36 months follow-up was 43.3%.     

Pegylated liposomal doxorubicin, 5-fluorouracil and cisplatin versus mitomycin-C, 5-fluorouracil and cisplatin for advanced gastric cancer: a randomized phase II trial

Purpose  

Clinical data suggested that a regimen incorporating doxorubicin to 5-fluorouracil (5-FU) and cisplatin may be more effective but probably quite toxic for advanced gastric cancer patients. With the aim to maintain efficacy while reducing toxicity, we compared the activity and safety of a combination of 5-FU, cisplatin and pegylated liposomal doxorubicin with a combination of 5-FU, cisplatin and mitomycin-C.     

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.     

多西紫杉醇联合顺铂、5-氟尿嘧啶治疗晚期胃癌34例临床分析

目的:评价多西紫杉醇联合顺铂、5-氟尿嘧啶方案(DCF方案)治疗晚期胃癌的临床疗效和不良反应.方法:DCF方案治疗晚期胃癌患者37例.多西紫杉醇45mg/m2,静滴1h,d1、8;5-氟尿嘧啶(5-FU) 375mg/m2,持续静脉泵(Graseby泵)点滴24h,d1-5;顺铂20mg/m2,d1-5;28天为1个周期.用药至少2个周期后评价疗效和不良反应.结果:全组34例可评价疗效,完全缓解(CR) 1例,部分缓解(PR) 14例,稳定(SD)15例,进展(PD)4例,有效率(RR)为44.1%.中位进展时间(TTP)为6.1个月,中位生存期为9.3个月,1年生存率28.2%.其中初治组有效率为52.6%(10/19),有1例CR;复治组有效率为33.3%(5/15),无CR病例,两组无显著差异(P>0.05).不良反应主要为骨髓抑制、消化系反应和脱发.大部分患者为Ⅰ、Ⅱ度反应,耐受良好.其中白细胞减少27例(79.4%),Ⅲ-Ⅳ度8例(23.5%).结论:多西紫杉醇联合顺铂、5-氟尿嘧啶组成DCF方案治疗进展期胃癌疗效较好,不良反应可以耐受,值得临床进一步探讨.     

Phase II trial of 5-fluorouracil,adriamycin and cisplatin (FAP) in advanced gastric cancer

Summary Twenty patients (15 male, 5 female) with nonresectable gastric adenocarcinoma were treated with FAP (5-fluorouracil 300 mg/m² IV on days 1–5, adriamycin 50 mg/m² IV on day 1, cisplatin 20 mg/m² IV on day 1–5). Each course was repeated every 21 days. Eighteen patients were evaluable for response. The median age was 51 years, the range extending from 34 to 68. None had undergone chemotherapy. The median Karnofsky performance score was 80%. Nine (50%) partial responses (PR) and eight (44%) cases of stable disease (SD) were observed. One patients showed progression of the disease and died after 6 months. The median duration of response was 6+ months for PR and 6 months for SD. The median survival was 12 months. FAP toxicity was moderate, with the median WBC nadir 3.2×10⁹/l (range 0.7–4.2). One patient in PR died of septicemia. Nausea and vomiting were not dose-limiting. Neuropathy was mild in four and moderate in two patients. This FAP combination appears to be as effective with respect to response rate and duration as reported for 5-fluorouracil, adriamycin and mitomycin C (FAM).     

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.     

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。     

Infusional 5-fluorouracil, cisplatin and mitomycin C in advanced gastric cancer: a low cost effective regimen

Recently, we reported a highly active regimen in advanced gastric cancer including a weekly administration of cisplatin, epidoxorubicin, leucovorin, 5-fluorouracil with the support of filgrastim. In order to simplify the administration and to decrease the toxicity of these drugs, mainly epidoxorubicin-induced alopecia, we designed a regimen including an infusional 5-fluorouracil schedule according to the de Gramont regimen, cisplatin and mitomycin C replacing epidoxorubicin. Forty-five patients with advanced or metastatic gastric cancer were treated with cisplatin 50 mg m(-2) i.v. on day 1, every 2 weeks, 6S-stereoisomer-leucovorin 100 mg m(-2) i.v. followed by 5-fluorouracil 400 mg m(-2) i.v. bolus and 600 mg m(-2) i.v. in a 22-h infusion, on days 1 and 2, every 2 weeks, and mitomycin C 7 mg m(-2) i.v. bolus on day 2, every 6 weeks. Grades 3-4 toxicities (National Cancer Institute-Common Toxicity Criteria) consisted mainly of neutropenia and thrombocytopenia. Five patients had a complete response and 16 had a partial response for an overall response rate of 46.7% (95% confidence interval, 32.1-61.2%). The median survival was 11 months. The combination of cisplatin, 5-fluorouracil and leucovorin according to de Gramont, and mitomycin C seems to be an active and safe regimen in the treatment of advanced gastric cancer. Because of its low cost it may be suggested for patients not enrolled into clinical trials.     

5-fluorouracil sensitivity and dihydropyrimidine dehydrogenase activity in advanced gastric cancer

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme of 5-fluorouracil (5-FU) catabolism. Several studies have demonstrated the clinical importance of DPD in cancer patients, suggesting that the efficacy of 5-FU may be related to DPD activity in tumor tissue. In the present study, DPD activity and chemosensitivity to 5-FU were evaluated in advanced gastric cancer. Materials and METHODS: Thirty-four gastric cancers from 32 patients were studied and chemosensitivity to 5-FU was evaluated by histoculture drug response assay. RESULTS AND CONCLUSION: DPD activity and tumor inhibition of 5-FU among all cases showed no significant correlation, but among 14 histologically differentiated cases significant correlation was observed. DPD activity may be useful in determining the 5-FU sensitivity of differentiated gastric 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。     

周剂量多烯紫杉醇联合顺铂和氟尿嘧啶治疗晚期胃癌的临床观察

目的:观察多烯紫杉醇联合顺铂和氟尿嘧啶治疗晚期胃癌的近期疗效和不良反应.方法: 全组49例患者,均经病理检查确诊为腺癌,肝转移13例,肺转移8例,腹腔淋巴结转移17例,腹膜转移7例,腹壁转移4例.应用多烯紫杉醇,顺铂,氟尿嘧啶(多烯紫杉醇25mg/m2静脉滴注1小时,第1、8、15天;顺铂25mg/m2静脉滴注1小时,第1-3天;氟尿嘧啶500mg/m2,持续静脉滴注120小时,第1-5天)方案治疗,28天重复.结果: 46例可评价疗效,总有效率为45.7%(21/46) ,完全缓解(CR)5例,部分缓解(PR)16例,稳定(SD)19例,进展(PD)6例.49例可评价毒性,主要的不良反应为骨髓抑制和胃肠道反应. 结论: 多烯紫杉醇联合顺铂和氟尿嘧啶方案对晚期胃癌患者疗效好,不良反应可耐受,值得临床推广应用.     

Treatment of advanced gastric cancer with DDP (cisplatin), adriamycin, and 5-fluorouracil (DAF)

Sixteen evaluable patients with advanced gastric cancer who had no prior therapy were treated intravenously with cisplatin (DDP) 20 mg/m2/day on days 1-5 and with Adriamycin 40 mg/m2 and 5-fluorouracil 600 mg/m2 on day 1 (DAF) every 3 weeks. There were five objective partial responses, giving a response rate of 31%. Five patients had minor responses, and 5 others achieved disease stabilization. The median duration of response for responders was 10 months, and the median time to tumor progression in nonresponders was 6 months. The overall median survival was 12 months (responders 14 months, nonresponders 9 months; NS). Most patients had a subjective improvement, including disappearance of abdominal pain (7/9) and gastrointestinal bleeding (5/7). The drug toxicity was moderate to severe. The primary nonhematologic toxicities were nausea and vomiting (in all patients), severe weakness (44%), and parasthesias (31%). Eight patients (50%) experienced significant bone marrow suppression. The DAF combination appears to have some activity in patients with advanced gastric cancer. However, further efforts in new drug development and other combinations are needed to improve the results of chemotherapy in stomach cancer.