Cisplatin, 5-fluorouracil,and high-dose leucovorin for advanced esophageal cancer

We report the effects and toxicities of intravenous administration of cisplatin, 5-FU and high-dose leucovorin for advanced esophageal cancer. Eight patients were registered and sixteen lesions were measurable. Of these sixteen lesions, thirteen were primary or synchronous metastatic lesions, and the response was 69%. Three were recurrence lesions, and the response rate for them was 0%. Including seven neoadjuvant cases, ten patients had oral mucositis, and seven patients had appetite loss. Other toxicities were diarrhea, myelosuppression, renal dysfunction, and alopecia. All were reversible after administration. It is suggested that this treatment regimen is a superior neoadjuvant chemotherapy with low toxicity.     

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%.     

Cisplatin and 5-fluorouracil for advanced locoregional and metastatic squamous cell carcinoma of the skin

Seven patients with advanced locoregional or metastatic squamous cell carcinoma of the skin were treated with cis-daimminedichloroplatin (cisplatin) and 5-fluorouracil (5-FU). Responses were seen in six of seven patients (three partial responses [PR] and three complete responses [CR]). One patient is alive and disease-free at 2 years. These results indicate that cisplatin and 5-FU is an effective combination regimen that should be used in future clinical trials in squamous cell carcinoma of the skin.     

Cisplatin and 5-fluorouracil chemotherapy in advanced or recurrent squamous cell carcinoma of the head and neck

Fifty-three patients with advanced or recurrent squamous cell carcinoma of the head and neck (SCCHN) were treated with bolus cisplatin (CDDP) and 96-hour infusion of 5-fluorouracil (5-FU). Twenty-six patients with advanced disease (21 T4 and/or N3) and no prior therapy (NPT) received 2 to 3 cycles of chemotherapy prior to surgery and/or radiation. There were four complete responses (CR) and 12 partial responses (PR) to chemotherapy for an overall response rate of 61%. In 20 patients with locally recurrent or disseminated disease there was one CR and six PR for an overall response rate of 35%. All but one responding patient in both groups showed clear evidence of tumor response after the initial cycle of chemotherapy. Two of the five complete responders required at least three courses to achieve CR. Disease-free survival was poor: only five of 26 patients in the NPT group remain alive and free of disease 8 to 28 months from initial therapy. CDDP and 5-FU is an active combination for SCCHN, but survival benefit remains to be proven.     

Cisplatin and 5-fluorouracil in refractory breast cancer patients: A phase II study

Summary 24 patients with a median of 3 prior chemotherapy regimens were treated in our department with cisplatin 20 mg/m² (with pre- and posthydration) and 5-fluorouracil 200 mg/m² i.v. on day 1–5, every three weeks. 23 patients are evaluable; one had early death. 4 patients (17%) achieved a partial response, 8 had stable disease, and 11 progressed. Toxicity observed was moderate and no renal toxicity was noted. This study therefore shows tolerable toxicity but limited usefulness of adding cisplatin to 5-fluorouracil according to this schedule in these highly pretreated patients.     

Nedaplatin and 5-fluorouracil combined with radiotherapy for advanced esophageal cancer

We conducted a pilot study of nedaplatin + 5-fluorouracil (5-FU) combined with radiotherapy for 29 patients with primary advanced (stage IV) esophageal cancer. A complete remission (CR) was obtained in 4 (14%) and a partial response in 13 patients (response rate: 59%). The median survival time and one-year survival rate were 238 days and 34.5%, respectively. Of the 29 patients, 24 (83%) completed the treatment schedule and toxicity of stomatitis and the like was infrequent. In conclusion, these results suggest that the efficacy of nedaplatin + 5-FU combined with radiotherapy might not differ from that of cisplatin + 5-FU combined with radiotherapy. Clearly, the usefulness of this combined therapy needs to be assessed in multicenter phase III trials.     

Intraperitoneal 5-fluorouracil in the management of colorectal liver cancer.

Twenty-five patients with colorectal liver metastases had a subcutaneous portal connection with a peritoneal catheter implanted for the intraperitoneal (i.p.) administration of 5-fluorouracil (5-FU). In five patients, the malignant disease rapidly progressed and the implanted catheter system was never used. Among the remaining 20 patients, seven patients had i.p. 5-FU as adjuvant treatment following liver resection and 13 patients received palliative chemotherapy (5-FU) owing to unresectable liver metastases. 5-FU was administered on a regular basis every 4 to 6 weeks by continuous infusion of 1000 mg/day (approximately 15 mg/kg/day) for 5 days. In seven patients, i.p. chemotherapy was managed on an outpatient basis. In general, i.p. 5-FU treatment was well tolerated with only minor abdominal complaints during the initial treatments. No definite effect on survival has been noted. All patients (n = 13) receiving palliative i.p. 5-FU died after a median of 4 (range 1.5-18) months. Two patients receiving adjuvant chemotherapy died owing to recurrence after 20 and 23 months, while five patients are alive, two with recurrent disease and three without, after 14-35 months.     

STAT3与原发性食管鳞癌关系的研究进展

目的:总结国内外STAT3与原发性食管鳞癌关系的研究进展.方法:检索Medline及CHKD期刊全文数据库检索系统,以"STAT3和肿瘤、STAT3和食管鳞癌"为关键词,检索1991-01-2009-12国内外STAT3与原发性食管鳞癌关系方面的文献,最后纳入分析29篇.结果:STAT3在食管鳞癌组织与细胞系中异常表达,并与肿瘤的增殖分化、细胞凋亡、血管新生、侵袭转移等密切相关.结论:STAT3信号通路在食管鳞癌发生、发展中起重要作用,以STAT3为靶点的治疗有望为食管鳞癌的治疗提供新的思路.     

Cisplatin and 5-fluorouracil infusion in patients with recurrent and disseminated epidermoid cancer of the head and neck

The combination of cisplatin and 96-hour infusion of 5-fluorouracil (5-FU) was evaluated in 30 patients with recurrent (local and regional) and disseminated histologically proven epidermoid cancer of the head and neck who failed surgery and radiotherapy. Cisplatin 100 mg/M2 intravenous (IV) bolus was given on day 1 with hydration and mannitol diuresis; 5-FU 1000 mg/M2 per day for 96-hour infusion was started immediately after cisplatin on day 1. All patients had measurable lesions. Eight (27%) patients achieved complete response (CR), and 13 (43%) had partial response (PR). Overall response rate was 70% (8 of 30 CR and 13 of 30 PR). Response rate in patients with recurrent local and regional disease was 89% (17/19) with median survival of 32 weeks, while response in patients with disseminated disease was 36% (4/11) with median survival of 24 weeks. Patients with good performance status (PS) (greater than or equal to 70%) had a response rate of 79% (19/24), while those with poor PS (less than 70%) had a response rate of 33% (2/6). Seven patients with recurrent disease who had a response to this chemotherapy went to further salvage surgical procedures. It is concluded that the combination of cisplatin and 5-FU is very effective and well tolerated in these patients, and leads to further salvage in some patients with improved longevity and quality of life.     

Concomitant 5-fluorouracil infusion, mitomycin C and radical radiation therapy in esophageal squamous cell carcinoma

This is a retrospective comparison of patients with unresected esophageal squamous cell carcinoma treated by radiation therapy and chemotherapy (21 patients) versus radiation therapy alone (34 patients). Pretreatment characteristics were comparable in both groups. In the combined modality group, treatment was given in split courses with concomitant radiation therapy (20 to 25 Gy in 10 fractions on days 1-12 and days 42-54) and chemotherapy (bolus Mitomycin C on day 1; 96 hr. of continuous 5 Fluorouracil infusion on days 1-4 and days 42-46). There was improvement in local disease control with the combined modality approach. Initial complete response was achieved in 86% of the radiation and chemotherapy group, versus 57% of the radiation alone group. The one-year local relapse-free rate was 67% versus 35%, and 2 year rate was 41% versus 28%. (p less than 0.05). The 1-year and 2-year survival was 64% and 32% respectively, for the radiation and chemotherapy group, versus 28% and 10% respectively for the radiation alone group (p less than 0.05). The majority of patients had disease relapsed, 81% of the combined modality group and 97% of the radiation alone group. However, the pattern of failure was different in the two groups. In the radiation and chemotherapy group, 29% had local failure alone, 53% had distant failure alone, and 18% had both local and distant failure. In the radiation alone group, 33% had local failure alone, 24% had distant failure alone, and 43% had both local and distant failure. Concomitant radiation therapy, 5 Fluorouracil infusion and bolus Mitomycin C is effective treatment for local control in esophageal squamous cell carcinoma, but not for distant hematogenous metastases. This combined modality treatment was well tolerated, with little additional hematological toxicity, esophagitis and stomatitis over radiation therapy alone.     

奈达铂联合氟尿嘧啶治疗中晚期食管癌的护理

目的探讨奈达铂(NDP)+氟尿嘧啶(5-Fu)方案治疗食管癌的护理体会。方法对27例中晚期食管癌患者实施化疗并采取相应的护理。结果完全缓解(CR)2例,部分缓解(PR)12例,稳定(SD)8例,进展(PD)5例。主要不良反应为恶心呕吐、骨髓抑制及肾功能损害。结论奈达铂联合氟尿嘧啶治疗中晚期食管癌配合相应的护理措施,可保证化疗疗程的顺利完成。     

多西他赛联合顺铂和5-氟尿嘧啶治疗晚期复治食管癌的临床疗效

目的探讨多西他赛联合顺铂和5-氟尿嘧啶治疗晚期复治食管癌的临床疗效。方法选取2012年5月至2016年5月间云南省肿瘤医院收治的80例晚期复治食管癌患者,采用等距随机抽样法分为观察组与对照组,每组40例。观察者患者采用多西他赛联合顺铂和5-氟尿嘧啶治疗,对照组患者采用多西他赛联合顺铂治疗,2个疗程后比较临床疗效。结果观察组患者治疗总有效率为62.5%,生活质量总分(88.14士1.21)分,对照组患者总有效率为47.5%,生活质量总分(75.33±1.25)分,两组比较差异均有统计学意义(均P<0.05);对照组患者不良反应发生率为15.0%,观察组患者为17.5%,两组比较差异无统计学意义(P>0.05)。结论多西他赛联合顺铂与5-氟尿嘧啶化疗方案治疗晚期复治食管癌疗效显著,可作为首选治疗方案推广使用。     

Cisplatin, 5-fluorouracil, mitomycin C, and concurrent radiation therapy with and without esophogectomy for esophageal carcinoma

Twenty-nine patients with carcinoma of the esophagus were treated with 5-fluorouracil (5-FU) (1000 mg/m2/d as a continuous intravenous [IV]infusion on days 1 through 4), cisplatin (100 mg/m2 IV on day 1), mitomycin C (10 mg/m2 IV on day 1), and concurrent radiation therapy (4500 cGy/4.5 wk). If no disease progression was observed, operable patients underwent surgery 4 to 6 weeks after completion of radiation therapy. A thoracotomy with a gastric pull-through operation was performed in the first six patients. Subsequently, a transhiatal ("blunt") esophagectomy was used. Twenty-five patients had squamous cell histology and four had adenocarcinoma. Of 25 patients with squamous cell carcinoma, 13 underwent esophagectomy. The clinical complete response rate was 61% (eight of 13 patients), with a pathologic complete remission documented in five of 13 patients (38%). The overall local tumor sterilization rate was 53% (seven of 13 patients). In the 12 patients who did not undergo surgery after chemoradiotherapy, four had a complete clinical response (33%) and five had a partial response (41%). Symptoms or signs of local disease recurrence or stricture were noticed in ten of 12 patients who did not undergo surgery (83%), compared with 28% of patients who underwent surgery. The median survival time of the group receiving surgery was 10 months, compared with 5 months for those who did not undergo operation (P = 0.027). Patients undergoing transhiatal esophagectomy had shorter postoperative hospital stays and fewer serious complications, compared with patients undergoing transthoracic esophagectomy. The use of chemoradiotherapy and transhiatal esophagectomy for esophageal carcinoma should be evaluated using alternative sequences of treatment (e.g., postoperative therapy) to reduce toxicity while maintaining local control of disease.     

Neoadjuvant chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil for esophageal cancer

Purpose

We aimed to evaluate the safety, tolerability, and efficacy of combination preoperative chemoradiotherapy as first-line treatment in patients with advanced esophageal cancer.

Methods

We performed a phase I dose-escalation trial of docetaxel at 25–40?mg/m² in four planned dose levels in 3–6 patient cohorts on days 1, 15, 29, and 43 administered in combination with cisplatin (70?mg/m² on days 1 and 29) and 5-fluorouracil (70?mg/m²/day on days 1–4 and 29–32) and concurrent radiation therapy (40?Gy). The tumors were resected during weeks 10–13.

Results

This study included 7 patients with esophageal cancer. The dose-limiting toxicity was observed at a biweekly docetaxel dose of 30?mg/m² when patients developed grade 3 febrile neutropenia, grade 4 thrombocytopenia, and grade 4 pain/esophagus, resulting in a maximum tolerated dose of 25?mg/m². Grade 3/4 hematological toxicity was observed in 71% of the patients and grade 3/4 non-hematological toxicity in 57%. The overall tumor response rate was 86% (complete, 57% and partial, 29%). All patients underwent surgery, and there were no deaths as a result of postoperative complications.

Conclusions

This preoperative chemoradiotherapy regimen using triplets is feasible but results in moderate toxicity. It is noteworthy that this regimen was associated with a high rate of pathological complete remission.     

Bcl-XL反义寡核苷酸增强食管癌细胞对5-氟尿嘧啶的敏感性

目的探讨Bcl -XL反义寡核苷酸(ASODN)在下调Bcl- XL表达、增加食管癌细胞株EC9706对5氟尿嘧啶(5Fu)敏感性中的作用。方法设细胞对照组、空白对照组、无关序列寡核苷酸(N ODN)组、ASODN组、5Fu组及ASODN联合5Fu组,应用四甲基偶氮唑蓝(MTT)法检测EC9706细胞的增殖抑制率;RT PCR和Westernblot检测Bcl- XLmRNA和蛋白表达水平的改变;吖啶橙荧光染色和流式细胞技术定量检测EC9706细胞的凋亡率。结果Bcl -XLASODN联合5Fu治疗组对食管癌细胞增殖的抑制率为71.58%,对Bcl XLmRNA表达抑制率为81.25%,并可显著下调Bcl XL的蛋白表达;凋亡指数为69.5%,凋亡率为(63.32±9.23)%,与细胞对照组、空白对照组、N -ODN组、ASODN组及5Fu组比较,差异均有统计学意义(P<0.05)。结论ASODN联合5Fu可有效抑制食管癌细胞EC9706的增殖,通过ASODN下调Bcl XL表达,可显著增强食管癌细胞对5Fu的敏感性。     

Relationship between gene expression of 5-fluorouracil metabolic enzymes and 5-fluorouracil sensitivity in primary cancer cells isolated from malignant ascites

This study was designed to investigate the predictive role of 5-FU metabolic enzymes in malignant ascites. Forty-three malignant ascites were collected and primary cancer cells were isolated. Gene expression was detected by quantitative RT-PCR. We found that DPD mRNA was higher in patients with pancreatic cancers than those with gastric cancers, colon cancers, and liver cancers. Significant correlations were found between expression of DPD and TP, and between TS and OPRT. mRNA levels of TS and OPRT correlated significantly with the chemosensitivity of 5-FU. Assessing gene expression would be useful in predicting 5-FU sensitivity for patients with malignant ascites.     

大剂量顺铂,氟脲嘧啶,平阳霉素治疗晚期食管癌临床观察

目的 观察大剂量顺铂（ＤＤＰ）、氟脲嘧啶（５－Ｆｕ）和平阳霉素（ＰＹＭ）联合化疗方案治疗晚期食管癌的疗效和安全性。方法 对５３例不能手术切除和无根治性放疗指征的晚期食管鳞癌患者,采用２组不同剂量的方案进行联合化疗。随机分为２组,治疗组每周期顺铂１２０ｍｇ／ｍ＾２、５－Ｆｕ１５００ｍｇ／ｍ＾２和ＰＹＭ３６ｍｇ／ｍ＾２,对照组剂量分别是６０ｍｇ／ｍ＾２、１０５０ｍｇ／ｍ＾２和ＰＹＭ３６ｍｇ／ｍ＾２,对     

奈达铂和顺铂联合氟尿嘧啶治疗中晚期食管癌疗效观察

目的: 观察双铂方案治疗中晚期食管癌的近期疗效及不良反应.方法: 60例病人随机分为两组,每组30例;治疗组:顺铂(PDD)15mg/(m2·d),d1-3天,奈达铂(NDP)50mg/m2,d5;亚叶酸钙(CF)70mg/(m2·d),d1-5天;氟尿嘧啶(5-Fu)500mg/(m2·d),d1-5天;对照组:顺铂(PDD)25mg/(m2·d),d1-3天;亚叶酸钙和氟尿嘧啶用法同治疗组.21天为1周期.结果: 治疗组:CR 3例,PR14例,SD9例,PD4例,有效率(RR)为56.7%(17/30);对照组:CR3例,PR12例,SD9例,PD6例,有效率(RR)50%(15/30),两组有效率相当(P>0.05);对照组呕吐的发生率明显高于治疗组(P<0.05).骨髓抑制,白细胞减少治疗组为56.7%,对照组为50%(P>0.05).血小板减少治疗组为10%,对照组为0(P<0.05).结论: 双铂方案联合氟尿嘧啶治疗中晚期食管癌疗效确切,副作用可耐受,值得进一步在临床中观察和研究.     

Nicotinamide N-methyltransferase decreases 5-fluorouracil sensitivity in human esophageal squamous cell carcinoma through metabolic reprogramming and promoting the Warburg effect

Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor with poor prognosis. And different individuals respond to the same drug differently. Increasing evidence has confirmed that metabolism reprogramming was involved in the drug sensitivity of tumor cells. However, the potential molecular mechanism of 5-fluorouracil (5-FU) sensitivity remains to be elucidated in ESCC cells. In this study, we found that the 5-FU sensitivity of TE1 cells was lower than that of EC1 and Eca109 cells. Gas chromatography-mass spectrometry analysis results showed that nicotinate and nicotinamide metabolism and tricarboxylic acid cycle were significantly different in these three cell lines. Nicotinamide N-methyltransferase (NNMT), a key enzyme of nicotinate and nicotinamide metabolism, was significantly higher expressed in TE1 cells than that in EC1 and Eca109 cells. Therefore, the function of NNMT on 5-FU sensitivity was analyzed in vitro and in vivo. NNMT downregulation significantly increased 5-FU sensitivity in TE1 cells. Meanwhile, the glucose consumption and lactate production were decreased, and the expression of glycolysis-related enzymes hexokinase 2, lactate dehydrogenase A, and phosphoglycerate mutase 1 were downregulated in NNMT knockdown TE1 cells. Besides, overexpression of NNMT in EC1 and Eca109 cells caused the opposite effects. Moreover, when glycolysis was inhibited by 2-deoxyglucose, the roles of NNMT on 5-FU sensitivity was weakened. In vivo experiments showed that NNMT knockdown significantly increased the sensitivity of xenografts to 5-FU and suppressed the Warburg effect. Overall, these results demonstrated that NNMT decreases 5-FU sensitivity in human ESCC cells through promoting the Warburg effect, suggesting that NNMT may contribute to predict the treatment effects of the clinical chemotherapy in ESCC.