Phase II study of epirubicin plus oxaliplatin and infusional 5-fluorouracil as first-line combination therapy in patients with metastatic or advanced gastric cancer

The purpose of this study was to evaluate the efficacy and safety of an epirubicin, oxaliplatin and infusional 5-fluorouracil combination in patients with advanced gastric cancer. Patients with previously untreated advanced measurable gastric cancer received epirubicin (50 mg/m2, day 1), oxaliplatin (130 mg/m2 2-h infusion, day 1) and 5-fluorouracil (750 mg/m2, 24-h infusion, day 1-3) every 3 weeks. The primary endpoint of this phase II study was the response rate according to Response Evaluation Criteria in Solid Tumors. Out of 48 patients, 46 were evaluable for efficacy and 48 for toxicity. A median of five cycles (range 1-6) was administered. The overall best response rate was 47.8% (95% confidence interval 33-63%) including 2.2% complete responses and 45.6% partial responses. The median time for progression and median overall survival was 5 (95% confidence interval 4.1-5.9) and 11 months (95% confidence interval 8.1-13.9), respectively. Grade 3/4 neutropenia and leukocytopenia were observed in 25 and 12.5% of patients, respectively. Grade 3/4 nonhematological toxicities included nausea (6.3%), vomiting (14.6%), neurological toxicity (10.4%) and mucositis (2.1%). The epirubicin, oxaliplatin and infusional 5-fluorouracil regimen was effective and well tolerated as a front-line chemotherapy for patients with metastatic or advanced gastric cancer, and should be evaluated further.     

紫杉醇联合奥沙利铂与卡培他滨联合奥沙利铂治疗晚期胃癌的疗效比较

目的 观察并比较紫杉醇联合奥沙利铂与卡培他滨联合奥沙利铂治疗晚期胃癌的近期疗效与不良反应.方法 回顾性分析54例晚期胃癌患者治疗情况,紫杉醇联合奥沙利铂组（A组）25例,卡培他滨联合奥沙利铂组（B组）29例.所有病例治疗4～8个周期后,评价其近期疗效及不良反应.结果 近期疗效评价,A组有效率为44.0%,B组有效率为41.2%,两组比较差异无统计学意义（P＞0.05）.主要不良反应为中性粒细胞减少、恶心呕吐、手足综合征、肝功能损害、外周神经毒性、脱发,其中A组中性粒细胞减少及脱发明显高于B组（P＜0.05）,B组手足综合征明显高于A组（P＜0.05）,其余不良反应两组差异无统计学意义（P＞0.05）,两组均无化疗相关性死亡.结论 两种方案近期疗效相当,不良反应均可耐受,均值得临床选择应用.     

A phase II trial of gefitinib in combination with capecitabine and oxaliplatin as first-line chemotherapy in patients with advanced colorectal cancer

ABSTRACT

Objective: This study was designed as a multicentre phase II trial to assess the efficacy and safety of gefitinib in association with capecitabine and oxaliplatin in patients with untreated metastatic colorectal cancer.

Research design and methods: Patients with metastatic colorectal cancer that had received no prior chemotherapy for advanced disease were treated with oral gefitinib (250?mg daily) plus oral capecitabine (1000?mg/m² twice a day on Days 1–14) and intravenous oxaliplatin (120?mg/m² on Day 1 of each 3?week cycle).

Results: Thirty-five patients were enrolled. In the intention-to-treat analysis, 3 (8.6%) patients experienced a complete response (CR), 14 (40%) a partial response (PR) and 11 (31.4%) had stable disease (SD). The disease control rate (CR + PR + SD) was 80%, the median time to progression was 7.3 months (95%CI: 4.76–9.2) and the estimated median overall survival was 21.9 months (95% CI: 15.1–not reached). The most common grade 3 to 4 toxicities included diarrhoea (31%) and vomiting (5.7%).

Conclusions: The combination of capecitabine, oxaliplatin and gefitinib appears to have promising activity in chemotherapy-naïve metastatic colorectal cancer. A higher disease control rate and an increase in median overall survival were seen compared with previous reports with capecitabine and oxaliplatin in similar patient populations. The tolerability profile appears to be predictable and similar to capecitabine/oxaliplatin regimens.     

奥沙利铂联合卡培他滨方案治疗老年晚期胃癌的临床观察

目的观察奥沙利铂联合卡培他滨方案治疗晚期胃癌的临床疗效及不良反应。方法 34例晚期老年胃癌患者,给予XELOX方案化疗,每21d为1周期,至少完成2个周期。评价客观疗效和不良反应。结果全组34例均可评价疗效,其中PR 14(41.2%),SD 10例(29.4%),PD 10例(29.4%)。中位肿瘤进展时间为5.2个月。化疗前ECOG评分与TTP显著相关。不良反应主要是骨髓抑制,胃肠道反应及外周神经毒性。结论奥沙利铂联合卡培他滨方案是治疗老年性晚期胃癌的有效方案,尤其适用于体力状况较好的患者。     

卡培他滨联合奥沙利铂治疗晚期胃癌临床分析

目的观察卡培他滨联合奥沙利铂治疗晚期胃癌的疗效及安全性。方法经病理证实的晚期胃癌患者,应用卡培他滨2000mg／m^2,分早晚2次口服,d1-d14,奥沙利铂130mg／m^2,静脉滴注,持续3h以上,d1,21天为1个周期。结果全组28例患者,获CR1例,PR14例,总有效率为53．6％,毒副反应以Ⅰ～Ⅱ度为主,出现Ⅲ度白细胞减少1例、血小板减少2例,恶心呕吐1例以及腹泻1例,无Ⅳ度毒副反应。结论卡培他滨联合奥沙利铂治疗晚期胃癌有效率较高,毒副反应较低,患者耐受性好。     

Mitomycin C plus S-1 as second-line therapy in patients with advanced gastric cancer: a noncomparative phase II study

S-1 is an oral fluoropyrimidine consisting of the 5-fluorouracil prodrug tegafur combined with two modulating substances, gimeracil and potassium oxonate. On the basis of the potential additive effect between mitomycin C (MMC) and 5-fluorouracil as a continuous infusion, we conducted a phase II study to assess the efficacy and tolerability of the combination of S-1 and MMC as second-line chemotherapy for advanced gastric cancer (AGC). Patients with measurable AGC, progressive after one prior chemotherapy for metastatic disease, received MMC (7 mg/m2) on day 1 and S-1 (40 mg/m2) twice daily as an intermittent regimen of 4 weeks of treatment followed by a 2-week rest. Treatment was repeated every 6 weeks. The primary objective was the response rate. For 43 patients registered, 42 patients were treated with MMC plus S-1. A total of 121 chemotherapy cycles were delivered (median: 2; range: 1-6). The patients' median age was 53 years (range: 31-75) and nine (21%) had an Eastern Cooperative Oncology Group performance status of 2. In an intent-to-treat analysis, nine patients (21%) achieved an objective response, which was maintained for 4.1 months. The median progression-free and overall survivals were 3.4 months (95% confidence interval: 2.3-4.5) and 8.0 months (95% confidence interval: 6.1-9.9), respectively. Although fatigue was the most frequently encountered toxicity safety profiles were generally predictable and manageable. One patient developed hemolytic anemia, which was resolved spontaneously. Grade > or = 2 hand-foot syndrome was observed in only three patients. Second-line chemotherapy with MMC and S-1 is an active and tolerable regimen for AGC patients with good performance status.     

奥沙利铂分别联合卡培他滨和替吉奥治疗晚期结直肠癌的临床疗效分析

目的 探讨奥沙利铂分别联合卡培他滨和替吉奥两种治疗方案对晚期结直肠癌的临床疗效及不良反应比较,为临床应用提供理论和实践的依据。方法 选取68例符合入组标准的晚期结直肠癌患者,按照用药方案的不同分成卡培他滨联合奥沙利铂治疗组(A组)35例,替吉奥联合奥沙利铂组(B组) 33例,通过观察两组方案的近期疗效、疾病进展时间及不良反应,分析评价两种方案的临床效果。结果 两种方案的近期疗效、疾病进展时间和不良反应发生情况,差异无统计学意义(P>0.05)。结论 卡培他滨联合奥沙利铂与替吉奥联合奥沙利铂治疗晚期结直肠癌疗效相当,不良反应差异无统计学意义,两种方案均可作为晚期结直肠癌患者治疗的较好选择。     

Phase I dose-finding study of sorafenib in combination with capecitabine and cisplatin as a first-line treatment in patients with advanced gastric cancer

Background To define maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs), and preliminary efficacy of sorafenib plus capecitabine/cisplatin in advanced gastric cancer (AGC) patients. Methods Four dose-level combinations were tested in a standard 3 + 3 dose escalation design. Level 1: sorafenib 400 mg/d, capecitabine 1,600 mg/m²/d, cisplatin 80 mg/m². Level 2: sorafenib 800 mg/d, capecitabine 1,600 mg/m²/d, cisplatin 80 mg/m². Level 3: sorafenib 800 mg/d, capecitabine 2,000 mg/m²/d, cisplatin 80 mg/m². Level 1A: sorafenib 800 mg/d, capecitabine 1,600 mg/m²/d, cisplatin 60 mg/m². Results There were 1 DLT at Level 2, and 2 DLTs at Level 3 (Level 3 was MTD). Since the relative dose intensity (RDI) of sorafenib and capecitabine could not be maintained at Level 2, Level 1A was newly investigated. As no DLT was observed and RDI remained above 80%, Level 1A is the recommended dose for the next clinical trial. Objective response rate was 62.5% (10 of 16 patients, 95% CI; 38.8–86.2%). Median progression-free survival and overall survival were 10.0 months (95% CI; 7.4–13.8) and 14.7 months (95% CI; 12.0–20.0), respectively. Conclusions Sorafenib 400 mg bid daily, capecitabine 800 mg/m² bid (days 1–14), and cisplatin 60 mg/m² (day 1) is recommended for further development in AGC.     

Phase II study of oxaliplatin in combination with continuous infusion of 5-fluorouracil/leucovorin as first-line chemotherapy in patients with advanced gastric cancer

This study was designed to determine the efficacy and safety of biweekly oxaliplatin in combination with infusional 5-fluouracil (5-FU) and leucovorin in patients with advanced gastric cancer (AGC). Fifty-five eligible patients with measurable or assessable M/AGC (median age 62 and 90% of patients presented with metastasis) received oxaliplatin (85 mg/m2) intravenous infusion for 2 h, followed by intravenous infusion of 5-FU (3000 mg/m2) and leucovorin (100 mg/m2) for 46 h every 14 days until the patient's disease was either in progression, unacceptable toxicity, patient's withdrawal or the investigators' decision to discontinue treatment. Of the 55 enrolled patients, 48 were evaluable for response. Three patients (5.4%) showed complete remission and 20 patients (36.4%) achieved partial response. The overall response rate was 47.9%. Nineteen patients (34.5%) had stable disease and six patients (10.9%) showed progressive disease. The median time to progression was 5.6 months and the median overall survival was 10.8 months. Grade 3/4 toxicities included leucopenia (12.7%), thrombocytopenia (5.4%), diarrhoea (3.6%) and vomiting (9.1%). Peripheral neuropathy was noted in 61.8% of the patients (grade 1/2: 54.5%; grade 3: 7.3%). Our study confirmed that the combination of oxaliplatin and continuous infusion of 5-FU/leucoverin without bolus 5-FU as first-line chemotherapy is active for patients with AGC and relatively safe with lower haematological toxicity.     

顺铂联合5-氟尿嘧啶与奥沙利铂联合替吉奥一线治疗晚期胃癌的对比研究

目的比较顺铂(DDP)联合5-氟尿嘧啶(5-FU)与奥沙利铂(L-OHP)联合替吉奥(S-1)一线治疗晚期胃癌的有效性和安全性。方法回顾性分析该院2009年1月-2012年11月间收治的53例晚期胃癌患者,其中A组(DDP+5-FU,PF组)25例,具体为:DDP 20 mg·m-2静滴,第1～5天,5-FU 500 mg·m-2静滴维持24 h第1～5天,每4周重复。B组(L-OHP+S-1)28例,具体为:L-OHP 130 mg·m-2静滴2 h,第1天,S-1 40 mg·m-2早晚2次餐后服用,第1～14天,每3周重复。每2个周期评价疗效及毒性。结果 53例患者均可评价毒副反应和近期疗效,44例可评价远期疗效。A组中有效率和疾病控制率分别为44%和56%,B组中有效率和疾病控制率分别为53.6%和89.3%,两组差异均无统计学意义(P0.05)。A组中位疾病进展时间(TTP)和中位总生存时间(MST)分别为4.5个月和10.7个月,B组中位TTP和中位MST分别为8.0个月和13.0个月。两组中位TTP差异有统计学意义(P=0.032),中位MST差异无统计学意义(P=0.172)。两组毒副反应主要有血液学异常、肝肾功能异常、恶心呕吐、神经毒性等,以1～2级为主,可耐受,B组轻度神经毒性发生率明显高于A组,差异有统计学意义(P=0.012)。结论 S-1+L-OHP方案一线治疗晚期胃癌,同PF方案相比中位疾病进展时间延长,毒副反应均可耐受,给药方便,值得临床进一步研究。     

卡培他滨单药及联合奥沙利铂方案治疗老年晚期胃癌的疗效比较

目的比较卡培他滨单药及联合奥沙利铂方案治疗老年晚期胃癌的疗效及安全性。方法 46例老年晚期胃癌患者随机分为对照组和治疗组,分别应用卡培他滨单药及联合奥沙利铂方案治疗,21d为一个周期。治疗2个周期按RECIST标准评价,并比较两组的近期疗效及毒副反应。结果对照组和治疗组有效率分别为31.82%和50.00%,中位疾病进展时间(TTP)分别为4.2个月和6.1个月,中位生存期(OS))分别为8.7个月和11.9个月。治疗组高于对照组,但两组有效率比较无统计学意义(P>0.05);主要毒副反应为手足综合征、恶心呕吐、腹泻、口腔炎症、白细胞减少及神经毒性等,一般为Ⅰ～Ⅱ度,均可耐受。结论两种方案治疗老年晚期胃癌有效率高疗效相近,但联合治疗组有更长生存期趋势,有待于进一步研究。     

奥沙利铂联合卡培他滨治疗晚期胃癌的价值分析

目的 探讨奥沙利铂联合卡培他滨治疗晚期胃癌的临床价值.方法 将西安医学院附属医院66例晚期胃癌患者按随机数字表法分为观察组和对照组,每组33例.观察组患者给予奥沙利铂130 mg/m2静脉滴注,口服卡培他滨2 500 mg/（m2＆#183;d）.对照组患者给予顺铂20 mg/m2静脉滴注,口服亚叶酸钙200 mg/m2;微量泵输入氟尿嘧啶2 400 mg/m2,共46 h.治疗2个周期后观察2组患者的临床疗效、生存质量及药物不良反应.结果 观察组总有效率为54.5％（18/33）,明显高于对照组的33.3％（11/33）,差异有统计学意义（P＜0.05）.2组治疗后生活质量评分均明显高于治疗前[观察组：（88±8）分比（65±7）分;对照组：（79±9）分比（66±7）分],差异有统计学意义（P＜0.05）.观察组治疗后的生活质量与对照组比较,差异有统计学意义（P＜0.05）.观察组的中性粒细胞减少、血红蛋白降低、血小板减少、外周神经毒性、恶心呕吐、腹泻等Ⅲ～Ⅳ级不良反应发生率明显低于对照组,差异有统计学意义[30.3％（10/33）比3.0％（1/33）、27.3％（9/33）比0.0％、21.2％（7/33）比0.0％、24.2％ （8/33）比0.0％、24.2％（12/33）比0.0％、21.2％（7/33）比0.0％]（P＜0.05）.2组手足综合征、口腔黏膜炎Ⅲ～Ⅳ级不良反应发生率比较,差异无统计学意义（P＞0.05）.结论 奥沙利铂联合卡培他滨能有效地治疗晚期胃癌,且能提高患者的生活质量.     

Multicenter phase II study of brequinar sodium in patients with advanced gastrointestinal cancer

Summary Eighty-six patients with advanced colorectal, gastric or pancreatic carcinoma and no prior exposure to chemotherapy were treated with brequinar sodium. Brequinar was administered at a median weekly dose of 1200 mg/m² intravenously. The toxicity was moderate, with thirty patients (35%) experiencing grade 3 or 4 toxicity. Objective responses were observed in 1/32 evaluable colorectal and 2/29 evaluable gastric carcinoma patients. There were no objective responses in 17 evaluable pancreatic cancer patients. We conclude that, at this dose and schedule, brequinar does not have sufficient activity in these gastrointestinal malignancies to warrant further evaluation.     

紫杉醇联合奥沙利铂和卡培他滨治疗晚期胃癌

目的探讨紫杉醇联合奥沙利铂和卡培他滨治疗晚期胃癌的疗效和不良反应。方法选择南阳市中心医院2007年5月—2010年l2月收治的30例晚期胃癌患者,采用紫杉醇联合奥沙利铂和卡培他滨方案治疗:紫杉醇75mg/m2,第1、8d,静脉滴注;奥沙利铂130mg/m2,第1d,静脉滴注;卡培他滨800mg/m2第1～14d,分两次口服,21d为1周期。两个周期评价疗效。结果全组30例均可评价疗效,其中PR 14例,SD 8例,PD 8例,客观有效率为73.3%;中位肿瘤进展时间为6.1个月,中位总生存期为10.5个月。不良反应主要为骨髓抑制、恶心呕吐和外周神经毒性。结论紫杉醇联合奥沙利铂和卡培他滨治疗晚期胃癌疗效较好,不良反应可耐受,值得临床进一步研究。