Phase II study of paclitaxel, cisplatin, and 5-fluorouracil combination chemotherapy in patients with advanced gastric cancer

This phase II study evaluated the efficacy and safety of combination chemotherapy with paclitaxel, cisplatin, and 5-fluorouracil (5-FU) in advanced gastric cancer. Patients with histologically confirmed gastric adenocarcinoma were eligible for the study. Paclitaxel (175 mg/m(2)) and cisplatin (75 mg/m(2)) were given as a 1-hr intravenous infusion on day 1, followed by 5-FU (750 mg/m(2)) as a 24-hr continuous infusion for 5 days. This cycle was repeated every 3 weeks. Forty-five eligible patients (median age, 56 yr) were treated in this way. Of the 41 patients in whom efficacy was evaluable, an objective response rate (ORR) was seen in 51.2% (95% CI, 0.35-0.67), a complete response in two, and a partial response in 19 patients. The median progression free survival was 6.9 months (95% CI, 5.86-7.94 months), and the median overall survival was 12.7 months (95% CI, 9.9-15.5). The main hematological toxicity was neutropenia and greater than grade 3 neutropenia was observed in twelve patients (54%). Febrile neutropenia developed in three patients (6.8%). The major non-hematological toxicities were asthenia and peripheral neuropathy, but most of patients showed grade 1 or 2. In conclusion, combination chemotherapy with paclitaxel, cisplatin, and 5-FU is a promising regimen, and was well tolerated in patients with advanced gastric cancer.     

Replacement of cisplatin with nedaplatin in a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma

Objective: The effects of replacing cisplatin (CDDP) with cis-diammineglycolatoplatinum (nedaplatin, NDP), a second-generation platinum complex, on the pharmacokinetics of 5-fluorouracil (5-FU) were investigated in Japanese patients with esophageal squamous cell carcinoma, who were treated with a definitive 5-FU/CDDP-based chemoradiotherapy.Methods: Fifty-six patients were enrolled, 49 treated with CDDP and 7 treated with NDP. A course consisted of continuous infusion of 5-FU at 400 mg/m²/day for days 1-5 and 8-12, infusion of CDDP or NDP at 40 mg/m²/day on days 1 and 8, and radiation at 2 Gy/day on days 1 to 5, 8 to 12, and 15 to 19, with a second course repeated after a 2-week interval. Plasma concentrations of 5-FU were determined by high performance liquid chromatography at 5 PM on days 3, 10, 38 and45, and at 5 AM on days 4, 11, 39 and 46.Results and conclusions: The circadian rhythm in plasma concentrations of 5-FU observed in the case of CDDP was altered when NDP was used instead. The clinical response can be predicted by monitoring plasma concentrations of 5-FU in the CDDP group, but not in the NDP group.     

影响二次放疗食管癌预后的因素分析

目的:探讨影响二次放疗食管癌预后的因素.方法:14例食管癌放疗后复发患者接受二次放疗.给予三维适形放疗,分别采用单因素和多因素风险模型进行COX风险比例分析,最后采用Kaplan-Meier生存分析和Log-Rank检验分析影响二次放疗食管癌的预后因素.结果:单因素分析显示肿瘤原发部位是影响预后的因素;多因素分析显示肿瘤长度和分化程度是影响生存时间的主要因素;Kaplan-Meier生存分析和Log-Rank检验分析显示影响二次放疗食管癌患者生存率的危险因素是肿瘤分化程度,高分化患者生存时间明显优于中低分化.结论:分化程度是影响二次放疗食管癌的主要预后因素.     

Bi-weekly chemotherapy of paclitaxel and cisplatin in patients with metastatic or recurrent esophageal cancer

Although various combinations of chemotherapy regimens have been tried for patients with esophageal cancer, their duration of survival is extremely poor. In this study, we investigated the safety and clinical efficacy of paclitaxel and cisplatin chemotherapy in metastatic or recurrent esophageal cancer. 32 patients enrolled in this study and the median age was 60 yr. Of all the 32, 28 patients (88%) had been treated previously, 22 of them with chemotherapy or radiation therapy. All patients in the study received biweekly paclitaxel (90 mg/m(2)) followed by cisplatin (50 mg/m(2)). One patient (3%) responded completely, and 12 patients (38%) showed a partial response; in 9 patients (28%) the disease remained stable, and in 10 patients (31%) it progressed. The objective response rate was 41%. The median duration of response was 4.8 months, and the median overall survival in all patients was 7 months. The 1-yr and 2-yr survival rates were 28.1% and 7.1%, respectively. Grade 3 or 4 of neutropenia and anemia were observed in 6 (19%) and 5 (16%) patients, respectively. The major non-hematologic toxicity was fatigue, but most of them could manageable. In conclusion, biweekly paclitaxel and cisplatin is effective in patients with metastatic or recurrent esophageal cancer.     

三维适形放射治疗同步周剂量TP方案化学治疗中晚期食管癌的临床研究

目的探讨三维适形放射治疗同步周剂量化学治疗在中晚期食管癌治疗中的近期有效率、不良反应及生存率。方法选择80例中晚期食管癌患者,根据入选标准进入研究,其中男性52例,女性28例;年龄56～82岁,中位年龄66岁。随机分为2组,三维适形放射治疗同步周剂量TP方案化学治疗组（放化疗组）28例;单纯三维适形放射治疗组（单放组）52例。放化疗组采用三维适形放射治疗,常规分割,每次2 Gy,1次/天,5天/周,放疗剂量60～66 Gy,同步给予TP方案,组成及用法：顺铂20～30mg/m2,第1、2天和第8、9天静脉滴注;紫杉醇90 mg/m2,第1天、第8天静脉滴注;28 d为1个周期,共2～4个周期。单放组采用单纯三维适形放射治疗,放射剂量同放化疗组。结果放化疗组近期有效率为96.4%,单放组为96.2%,两组比较,差异无统计学意义（P〉0.05）。放化疗组1年、2年、3年生存率分别为73.5%、68.8%、49.7%,1年、2年、3年局部控制率分别为86.8%、72.7%、60.3%;单放组1年、2年、3年生存率分别为69.5%、50.9%、35.6%,1年、2年、3年局部控制率分别为71.6%、55.4%、47.8%。两组患者1年生存率差异无统计学意义,2年、3年生存率及1年、2年、3年局部控制率差异均有统计学意义。放化疗组不良反应主要是放射性食管炎、消化道反应和血液毒性,患者均能耐受。结论三维适形放射治疗同步周剂量TP方案化学治疗对中晚期食管癌近期疗效及生存率较好,虽不良反应增加但患者可以耐受。     

Daily low-dose cisplatin and concurrent thoracic irradiation for poor-risk patients with unresectable non-small-cell lung cancer

A pilot study was conducted to assess the efficacy and feasibility of daily low-dose cisplatin with concurrent thoracic irradiation for clinically unresectable non-small-cell lung cancer (NSCLC). Patients with inoperable NSCLC who had poor risk factors such as advanced age, poor performance status, poor lung function, or concomitant active malignancy were entered into the study. Low-dose cisplatin (6 mg/m2) was administered daily before concurrent thoracic irradiation (2 Gy/day; total dose of 60 Gy) was given. Twenty-five patients were registered. The majority of the patients had either stage IIIA (24.0%) or stage IIIB (60.0%) disease. Fifteen patients (60.0%) completed the planned treatment. Both chemotherapy and radiotherapy were stopped in 3 patients (12.0%) due to poor response, and 7 patients (28.0%) partly received radiotherapy alone as a result of their toxicity response. The proportion of total administered dose to planned dose was 90.9% for chemotherapy and 99.3% for radiotherapy, which were comparable to those in previous studies for LA-NSCLC patients without poor risk factors. Grade 3 leukopenia and neutropenia developed in 14 patients (56.0%) and 10 patients (40.0%), respectively, but grade 4 toxicity was not encountered. Grade 3 pneumonitis and esophagitis were observed in 4 patients (16.0%) and 2 patients (8.0%), respectively. The overall response rate was 60.0%. The median survival time was 22 months, and the 2-year survival rate was 50.3%. Daily low-dose cisplatin and concurrent thoracic irradiation were well tolerated even by poor-risk patients with NSCLC, and showed a therapeutic efficacy similar to that for good-risk patients.     

多西他赛联合顺铂及氟尿嘧啶(DCF)改良方案治疗晚期胃癌疗效观察

目的 研究多西他赛联合顺铂及氟尿嘧啶改良方案(mDCF)治疗晚期胃癌的疗效及安全性.方法 2006年1月起,采用改良DCF方案治疗45例晚期胃癌患者.化疗方案:多西他赛60 mg/m2,d1;顺铂12 mg/m2,d1 ～5;氟尿嘧啶2500 mg/m2,持续输注(civ) 120 h;每21天一个周期.主要研究终点:无进展生存期(PFS).次要研究终点:总生存期(OS),总缓解率(ORR)及不良反应.结果 接受一线解救化疗患者40例,完全缓解0例(0％),部分缓解7例(17.5％),疾病稳定19例(47.5％),疾病进展14例(35.0％),总缓解率17.5％(95％ CI 7.5％ ～30.0％),疾病控制率65.0％ (95％ CI 50.0％ ～77.5％).中位PFS 5.2个月(95％ CI 3.6～6.8月),中位OS 11.0个月(95％CI6.9～15.1月).接受二线解救化疗患者5例,疾病稳定3例,疾病进展2例,中位PFS 5.3个月(95％ CI 0 ～11.3月),中位OS 8.5个月(95％ CI0～17.1月).主要不良反应为血液学毒性,Ⅲ～Ⅳ度粒细胞减少及粒细胞减少伴发热发生率分别为26.7％及11.1％,Ⅲ～Ⅳ度恶心、呕吐及腹泻发生率分别为8.9％、8.9％及11.1％.结论 改良DCF方案有效,不良反应可耐受.     

Effects of bolus injection of 5-fluorouracil on steady-state plasma concentrations of 5-fluorouracil in Japanese patients with advanced colorectal cancer

Objectives: The irinotecan (CPT-11) + 5-fluorouracil (5-FU)/leucovorin (LV) + UFT/LV chemotherapy, in which repetitive oral administration of UFT/LV replaces the infusion of 5-FU/LV in the FOLFIRI regimen, has been proposed previously. In this study, five of 10 patients were injected with a bolus of 5-FU and the other were not injected with it in order to examine the effect of omitting it in terms of pharmacokinetics of 5-FU.Methods: The treatment consisted of the intravenous infusions of CPT-11 at 100 mg/m² and l-LV at 15 mg/m², and the injection of a bolus of 5-FU at 500 mg/m² on day 1, and the repetitive oral administration of UFT/LV (300 mg/m²/day as tegafur + 75 mg/day of LV) on days 1-5. A total of 13 measurements of the plasma concentrations of uracil, 5-FU and tegafur were made per patient within 48 hr after the start of chemotherapy and the value of area under the concentration-time curve (AUC_0-48) was evaluated. The plasma concentration was also determined at 2 weeks to assess long-term exposure to 5-FU.Results: The plasma concentrations of 5-FU at 24 hr after the start of treatment were 27.4 ng/mL and 9.4 ng/mL in the patients with and without the bolus injection, respectively. At 48 hr, they were 31.3 ng/mL and 10.4 ng/mL with the AUC_0-48 values of 22.16 mg*h/L and 0.65 mg*h/L, respectively. The 5-FU was detected in the plasma at 226 hr after the last administration of UFT/LV for the patients with the bolus injection, but not for those without.Conclusion: A bolus of 5-FU on day 1 provided long-term exposure to 5-FU.     

Combination chemotherapy with 5-fluorouracil and heptaplatin as first-line treatment in patients with advanced gastric cancer

Heptaplatin is a recently developed platinum derivative. This agent has been reported to have a response rate of 17% as a single agent, and tolerable toxicity in the treatment of advanced gastric cancer. The aim of this study was to evaluate the efficacy and toxicity of a combination of 5-fluorouracil (5-FU) and heptaplatin in patients with advanced gastric cancer. Forty-seven chemotherapy-naive patients with advanced or recurred gastric cancer were recruited. 5-FU was administered over 120 hr by continuous intravenous infusion from day 1 to 5, at a daily dose of 1,000 mg/m2 and heptaplatin was administered over 1 hr by intravenous infusion on day 1 at 400 mg/m2, and this cycle was repeated every 4 weeks. The response rate was 21%, median progression-free survival was 1.9 months (95% CI, 1.6 to 2.2 months). Median overall survival was 6.2 months (95% CI, 4 to 8.4 months) and the 1-yr survival rate was 29% for all patients. The most frequent toxicity was proteinuria. Toxicities were generally mild and reversible. This study demonstrates that the combination of 5-FU/heptaplatin combination is less active but tolerated in patients with advance gastric cancer.     

Paclitaxel or 5-fluorouracil/esophageal stent combinations as a novel approach for the treatment of esophageal cancer

Currently, esophageal cancer is rarely curable, and herein, a paclitaxel or 5-fluorouracil/esophageal stent combination (PTX or 5-FU/stent) was used to provide a new approach to treat this cancer. The PTX or 5-FU/stent was prepared by covering a nitinol stent with a bilayered polymer film that consisted of a layer of 50% PTX or 5-FU and a layer of drug-free backing. These treatment modalities were evaluated in vivo after implantation into the porcine esophagus. The percentages of the drugs that permeated from the backing layer over a period of 95 days were very small (0.61% for 5-FU), and an overwhelming majority of the PTX and the 5-FU was released from the other side of the film. During the follow-up period (120 days), the drug/stent was always maintained in the porcine esophagus, and did not show any obvious systemic or local toxicities. In contrast, this treatment had an effect on the inhibition of tissue proliferation and ulceration. In addition, the drug concentrations were highest in the esophagus compared with in the heart, liver, spleen, lung, kidney and blood (81500.0 ± 9475.2 ng/g vs. 3.9 ± 0.3 ng/mL of PTX in the plasma at 13 days). The PTX/stent and the 5-FU/stent have a dual function as both a stent and a local drug delivery device, which provides a potential treatment modality with high efficacy and non systematic toxicity for esophageal cancer.     

同步放化疗与单纯放疗对鼻咽癌患者近期及远期影响

目的：探讨同步放化疗与单纯放疗对鼻咽癌患者近期及远期影响。方法：选取我院2008年2月至2010年2月的156例鼻咽癌患者进行研究,随机分为同步放化疗组和单纯放疗组各78例,同步放化疗组采用奥沙利铂联合贝伐单抗与卡培他滨化疗2周期再进行放疗,单纯放疗组采用顺铂单纯放疗,观察两组患者的治疗效果,1、3、5年的生存率和局部控制率,并发症等指标。结果：同步放化疗组的有效率(92.3%)明显高于单纯放疗组(79.5%),具有统计学意义(χ2=5.987,P<0.05);同步化放疗组1、3、5年的局部控制率(76.9%、62.8%、48.7%)明显高于单纯放疗组(62.8%、48.7%、38.5%),具有统计学意义(χ2=5.696,P=0.031;χ2=5.595,P=0.032;χ2=5.512,P=0.039);同步化放疗组的1、3、5年的生存率(66.7%、56.4%、46.2%)明显高于单纯放疗组(56.4%、46.2%、35.9%),具有统计学意义(χ2=5.396,P=0.033;χ2=5.356,P=0.034;χ2=5.445,P=0.031);同步化放疗组的并发症发生率(5.1%)明显低于单纯放疗组(28.2%),具有统计学意义(χ2=5.968,P<0.05)结论：对鼻咽癌患者进行同步化放疗能更好的控制病情,提高患者的生存率,减少不良反应的发生,比较安全。     

同步放疗联合奈达铂、紫杉醇治疗宫颈癌的临床分析

目的研究分析同步放疗联合奈达铂、紫杉醇治疗宫颈癌的临床效果。方法临床选择64例宫颈癌患者随机分成两组,每组32例,对照组患者给予单纯放疗治疗,而研究组在对照组治疗的基础上同时给予奈达铂、紫杉醇治疗。治疗后观察分析两组患者的相关临床资料情况。结果治疗3个月后,对照组与研究组的总有效率分别为31.25%和75%,两组之间具有统计学差异（P〈0.05）。随访1年,对照组的总生存率（68.75%）、无远处转移生存率（62.5%）及无局部复发率（62.5%）,与研究组的总生存率（90.63%）、无远处转移生存率（87.5%）及无局部复发率（81.25%）比较,均具有统计学差异（P〈0.05）。两组患者均出现了不同程度的不良反应,但在予以相应的对症支持治疗后好转。结论同步放疗联合奈达铂、紫杉醇治疗宫颈癌不仅疗效显著,而且具有一定的安全性。     

中晚期食管癌患者经艾迪注射液联合放化疗治疗的临床疗效研究

目的：研究分析中晚期食管癌患者经艾迪注射液联合放化疗治疗的临床疗效。方法：选取在我院治疗的中晚期食管癌患者92例(2013年9月到2015年9月)。将其动态随机化分2组,研究组和对照组各46例。对照组患者给予同步放化疗治疗,研究组患者在同步放化疗的基础上联合使用艾迪注射液治疗,对比两组患者的临床疗效、生活质量与免疫变化情况。结果：研究组患者的总缓解率为80.43%、提高稳定率达到了76.09%,治疗后CD3+T细胞76.16%±6.61%、CD4+T细胞35.71%±4.33%、CD8+T细胞36.27%±9.13%,与对照组比较均有明显优势,P<0.05。结论：采用艾迪注射液与放化疗结合的方式对中晚期食管癌患者进行治疗的效果显著,可以广泛应用于临床上。     

不同放疗剂量治疗80岁以上高龄食管癌患者的预后分析

目的:回顾性分析不同放疗剂量治疗80岁以上高龄食管癌临床疗效、安全性和影响因素。方法:回顾性分析2013年7月~2016年9月间行调强放疗的83例80岁以上高龄食管癌的临床资料,Kaplan-Meier法计算总生存率（OS）和无进展生存率（PFS）,Log-rank法检验单因素预后分析和Cox回归模型检验多因素预后分析。结果:中位随访时间37.2月,1、2和3年OS分别为68.7%、46.7%和32.1%,1、2、3年PFS率分别为61.1%、40.0%和24.7%,中位OS和PFS分别为24.1月和19.4月。单因素分析显示影响OS和PFS的临床因素有放疗剂量（P=0.006和0.013）,老年营养风险指数（GNRI）（P=0.002和0.007）和成人合并症评估-27（ACE-27）评分（P=0.018和0.040）。多因素分析显示放疗剂量（P=0.015和0.029）和GNRI（P=0.007和0.019）是OS和PFS的独立预后因素。高剂量“≥60 Gy”组患者3级以上不良反应发生率为57.1%,高于低剂量“<54 Gy”组的25.0%（P=0.037）和较高剂量“54~60 Gy”组的26.2%（P=0.016）。结论:调强放疗治疗80岁以上高龄食管癌患者耐受性尚可,患者营养状态和放疗剂量是影响患者预后的主要因素,较高剂量“54~60 Gy”组预后较好且治疗毒副反应较轻,可作为高龄食管癌优选放疗剂量。     

不同剂量调强放疗联合同步化疗对局部晚期肺癌患者生存期和毒副反应的影响

目的:探讨不同剂量调强放疗联合同步化疗对局部晚期肺癌患者生存期和毒副反应的影响。方法:选取96例确诊为局部晚期肺癌患者为研究对象,随机分为对照组（n=48）和观察组（n=48）。对照组采用62 Gy调强放疗联合PC同步化疗,观察组调整放疗剂量为50 Gy。记录患者临床一般资料。K-M分析绘制生存曲线,Log Rank [χ2]检验比较生存率,记录两组患者治疗1个月后毒副反应发生情况。结果:观察组和对照组患者缓解率无显著差异（75.00% vs79.17%, P>0.05）;观察组患者总生存率和无进展生存率均高于对照组（P<0.05）,中位生存时间显著长于对照组（P<0.05）。观察组骨髓抑制和放射性肺炎等放疗毒副反应发生率显著低于对照组（P<0.05）。结论:通过降低调强放疗剂量能够减轻患者毒副反应,提高患者生存期,联合同步化疗能够发挥良好的临床缓解效应。     

20例胸中段食管癌根治性放射治疗IMRT与TOMO剂量学比较

目的:对比固定野静态调强放射治疗（IMRT）与螺旋断层放射治疗（TOMO）两种方案治疗胸中段食管癌的剂量学特点,指导临床治疗方案选择。 方法:采用IMRT与TOMO两种技术,处方剂量计划靶区（PTV）:DT 54 Gy/30 F,肿瘤靶区（PGTV）:DT 66 Gy/30 F,主要比较两种方案的靶区剂量学差异。 结果:TOMO组的PTV最大剂量（D2）、中位剂量（D50）以及均匀性指数均低于IMRT组,最小剂量（D98）、适形度指数明显高于IMRT组,以上差异均有统计学意义（P<0.05）;两者的PGTV除D98的差异无明显统计学意义外,其余各指标均与PTV保持一致,有统计学意义（P<0.05）。 结论:胸中段食管癌根治性放射治疗TOMO计划靶区剂量分布及适形度明显优于IMRT计划,危及器官各评级指标显示前者亦优于后者。