Phase I/II study of S-1 combined with paclitaxel in patients with unresectable and/or recurrent advanced gastric cancer

Both paclitaxel and S-1 are effective against gastric cancer, but the optimal regimen for combined chemotherapy with these drugs remains unclear. This phase I/II study was designed to determine the maximum tolerated dose (MTD), recommended dose (RD), dose-limiting toxicity (DLT), and objective response rate of paclitaxel in combination with S-1. S-1 was administered orally at a fixed dose of 80 mg m-2 day-1 from days 1 to 14 of a 28-day cycle. Paclitaxel was given intravenously on days 1, 8, and 15, starting with a dose of 40 mg m-2 day-1. The dose was increased in a stepwise manner to 70 mg m-2. Treatment was repeated every 4 weeks unless disease progression was confirmed. In the phase I portion, 17 patients were enrolled. The MTD of paclitaxel was estimated to be 70 mg m-2 because 40% of the patients given this dose level (two of five) had DLT. The RD was determined to be 60 mg m-2. In the phase II portion, 24 patients, including five with assessable disease who received the RD in the phase I portion, were evaluated. The median number of treatment courses was six (range: 1-17). The incidence of the worst-grade toxicity in patients given the RD was 28 and 8%, respectively. All toxic effects were manageable. The response rate was 54.1%, and the median survival time was 15.5 months. Our phase I/II trial showed that S-1 combined with paclitaxel is effective and well tolerated in patients with advanced gastric cancer.     

Phase I/II study of S-1 combined with irinotecan for metastatic advanced gastric cancer

A dose-escalation study of irinotecan (CPT-11) combined with S-1, an oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer (AGC). S-1 was administered orally at 80 mg m-2 day-1 from day 1 to 14 of a 28-day cycle and CPT-11 was given intravenously on day 1 and 8 at an initial dose of 70 mg m-2 day-1, stepping up to 100 mg m-2. The treatment was repeated every 4 weeks, unless disease progression was observed. In the phase I portion, the MTD of CPT-11 was presumed to be 100 mg m-2, because 66.6% of patients (two of three) developed DLTs. All three patients at the initial RD of CPT-11 (90 mg m-2) experienced grade 4 haematological or grade 3 nonhaematological toxicities at second course, followed by the dose reduction of CPT-11 from the third course. Considering safety and the ability to continue treatment, the final RD was determined to be 80 mg m-2. In the phase II portion, 42 patients including seven patients in the final RD phase I portion were evaluated. The median treatment course was five (range: 1-13). The incidences of severe (grade 3-4) haematological and nonhaematological toxicities were 19 and 10%, respectively, but all were manageable. The RR was 62% (26 of 42, 95% confidence interval: 47.2-76.6%), and the median survival time was 444 days. Our phase I/II trial showed S-1 combined with CPT-11 is effective for AGC and is well tolerated, with acceptable toxicity.     

Randomised phase II study of S-1/cisplatin plus TSU-68 vs S-1/cisplatin in patients with advanced gastric cancer

Background:

This study aimed to determine whether combination S-1 plus cisplatin (CDDP) therapy, the most widely used therapy for Japanese patients with advanced gastric cancer, and the novel oral antiangiogenic agent TSU-68 could contribute to gastric cancer treatment.

Methods:

Ninety-three patients with chemotherapy-naïve unresectable or recurrent advanced gastric cancers were randomised into two groups: TSU-68 plus S-1/CDDP (group A) and S-1/CDDP (group B) groups. Both patient groups received identical S-1 and CDDP dosages. TSU-68 was orally administered for 35 consecutive days. Group B patients received S-1 orally twice daily for three consecutive weeks, followed by intravenous CDDP on day 8. The primary endpoint was progression-free survival (PFS).

Results:

Median PFS periods were 208 and 213 days in groups A and B, respectively (P=0.427). Median survival periods for groups A and B were 497.0 and 463.5 days, respectively (P=0.219). No statistically significant differences were noted for PFS, survival or the adverse event (AE) incidence rate. All AEs were expected according to previous reports for TSU-68, TS-1, and CDDP.

Conclusion:

Combination therapy involving TSU-68, S-1, and CDDP was safe and well tolerated in patients with chemotherapy-naïve unresectable or recurrent advanced gastric cancers. However, factors related to therapeutic efficacy should be investigated further.     

Phase I/II study of docetaxel and S-1 in patients with advanced gastric cancer

The aims of this phase I/II study of docetaxel and S-1 were to determine the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), and recommended dose (RD) in the phase I part and to explore the tumour response, survival and safety in the phase II part. Patients with histologically- or cytologically confirmed unresectable or recurrent gastric cancer were eligible. Treatment consisted of intravenous docetaxel on day 1 (starting dose 50 mg m(-2)) and oral S-1 at a fixed dose of 40 mg m(-2) twice daily on days 1-14, every 4 weeks up to six cycles. Nine patients took part in the phase I portion of the study. The MTD of docetaxel was determined to be 50 mg m(-2), with the DLTs of grade 3 infection associated with grade 3 neutropenia and grade 4 neutropenia during S-1 administration. The RD of docetaxel was 40 mg m(-2) in combination with S-1 40 mg m(-2) b.i.d. The efficacy and safety of this regimen was therefore assessed in 46 patients with at least one measurable lesion. The overall response rate and estimated median overall survival were 46% (95% CI, 31-61%) and 14.0 months (8.3-17.3 months), respectively. The most common grade 3/4 toxicity was neutropenia (67% of patients), which was predictable and manageable. This regimen showed promising activity with moderate toxicities in advanced gastric cancer.     

替吉奥联合顺铂治疗晚期胃癌的临床观察

目的观察替吉奥联合顺铂治疗晚期胃癌的近期疗效及不良反应。方法晚期胃癌患者27例,替吉奥根据体表面积给药,<1.25 m2,40 mg,bid;1.25～1.50 m2,50 mg,bid;>1.50 m2,60 mg,bid,早晚餐后口服,d1～14,顺铂;75 mg/m2,分d1、2,每21 d为1个周期,每完成2个周期评价疗效。结果 27例均可评价,其中完全缓解(CR)1例(3.7%),部分缓解(PR)14例(51.9%),稳定(SD)7例(25.9%),进展(PD)5例(18.5%),有效率(CR+PR)为55.6%(95%可信区间为35.5%～74.5%),疾病控制率(CR+PR+SD)为81.5%(95%可信区间为61.9%～93.6%)。主要不良反应表现为骨髓抑制、皮肤色素沉着及消化道反应。结论替吉奥联合顺铂治疗晚期胃癌近期疗效好,不良反应可以耐受,值得临床推广及进一步研究。     

Phase II multi-institutional prospective randomised trial comparing S-1+paclitaxel with S-1+cisplatin in patients with unresectable and/or recurrent advanced gastric cancer

Background:

A combination of S-1 and cisplatin has been shown to be effective with acceptable safety for the first-line treatment of far-advanced gastric cancer in Japan. This is the first randomised phase II trial to compare S-1+paclitaxel with S-1+cisplatin in this setting.

Methods:

Patients with unresectable and/or recurrent advanced gastric cancer were randomly assigned to receive one of the two regimens: S-1 (40 mg m⁻² twice daily) on days 1–14 plus paclitaxel (60 mg m⁻²) on days 1, 8, and 15 of a 4-week cycle (S-1+paclitaxel) or S-1 (40 mg m⁻² twice daily) on days 1–21 plus cisplatin (60 mg m⁻²) on day 8 of a 5-week cycle (S-1+cisplatin). The primary end point was the response rate (RR). Secondary end points included progression-free survival (PFS), overall survival (OS), and safety.

Results:

A total of 83 patients were eligible for safety and efficacy analyses. In the S-1+paclitaxel and S-1+cisplatin groups, RRs (52.3% vs 48.7% P=0.74) and median PFS (9 vs 6 months; P=0.50) were similar. The median OS was similar in the S-1+paclitaxel and S-1+cisplatin groups (16 vs 17 months; P=0.84). The incidence of grade 3 or higher haematological toxicity was 19.0% with S-1+paclitaxel and 19.5% with S-1+cisplatin. The incidence of grade 3 or higher non-haematological toxicity was 14.2% with S-1+paclitaxel and 17.1% with S-1+cisplatin.

Conclusion:

S-1+paclitaxel was suggested to be a feasible and effective non-platinum-based regimen for chemotherapy in patients with advanced gastric cancer. Our results should be confirmed in multicenter, phase III-controlled clinical trials.     

口服替吉奥联合三维适形放疗治疗局部晚期胃癌疗效观察

目的:评估口服替吉奥联合三维适形放疗治疗局部晚期胃癌的疗效和安全性。方法:38例局部晚期胃癌患者进入研究,采用口服替吉奥联合同步三维适形放疗方案治疗,替吉奥在放疗开始的第1天口服,剂量为40-60mg/m2,2次/天,连服2周,休息1周。维持替吉奥口服治疗至放疗结束后4周,评价治疗疗效和毒副反应。结果:全部38例患者均完成同步放化疗,其中完全缓解3例,部分缓解26例,稳定4例,疾病进展5例,总有效率为76.3%;患者进食梗阻、疼痛主观症状改善率分别为78.8%、84.6%。全组1年总生存率55.3%,2年总生存率31.5%。主要不良反应是I-III度消化道反应及血液学毒性,经对症支持治疗后好转。结论:口服替吉奥联合三维适形放疗方案治疗局部晚期胃癌可以提高患者生活质量,不良反应可耐受。     

A phase I/II study of S-1 plus cisplatin in patients with advanced gastric cancer: 2-week S-1 administration regimen

Background The combination of a new oral dihydropyrimidine dehydrogenase-inhibitory fluoropyrimidine (S-1) and cisplatin (CDDP) is one of the most active chemotherapy regimens for gastric cancer. However, the optimum schedule for this combination has not yet been determined. This study was conducted to establish the maximum tolerated dose (MTD) and the recommended dose of CDDP when combined with 2-week S-1 administration, and to observe the safety and efficacy of the regimen as treatment for patients with advanced gastric cancer.Methods S-1 was administered orally at a dose of 80mg/m² per day for 2 weeks, followed by a 2-week rest. CDDP was administered intravenously on day 8 of each course; the initial dose of CDDP was 60mg/m² and it was increased in 10-mg/m² increments. Treatment was repeated every 4 weeks unless disease progression was observed.Results Eleven patients were enrolled. The main toxicities were leucopenia, neutropenia, nausea, and anorexia. These toxicities were not severe, and were reversible and manageable. The MTD for CDDP was established as 80mg/m², as 2 of 5 (40%) patients developed dose-limiting toxicity (DLT) at this level. Therefore, the recommended dose of CDDP was determined to be 70mg/m². All 11 patients were evaluable for a response: 8 achieved a partial response and 1 had stable disease. The overall response rate was 73%.Conclusion This regimen is considered to be generally well-tolerated and has substantial antitumor activity.     

Phase II study of chemoradiotherapy with S-1 and low-dose cisplatin for inoperable advanced gastric cancer

PURPOSE: The results of a pilot study using S-1/low-dose cisplatin/radiotherapy led us to hypothesize that the initial chemoradiotherapy regimen would induce a 70% efficacy rate with a 10% pathologic complete response rate. PATIENTS AND METHODS: Only patients with unresectable or incurable advanced gastric cancer were eligible. The patients received induction S-1 and cisplatin therapy with radiotherapy followed by chemotherapy alone. RESULTS: Of the 30 patients recruited and assessed, 29 were eligible for clinical evaluation of measurable lesions. The response rate was 65.5%, with 19 with a partial response, 8 with no change, and 2 with progressive disease of 29 patients. Of the 30 patients recruited, 10 (33.3%) underwent stomach resection and D2 LN dissections. The pathologic complete response rate was 13.3% (4 patients), and the R0 resection rate was 100% (10 patients). The survival analysis showed a median survival time of 25 months. Grade 3 toxicity occurred in 66.7% for leukocytopenia, 33.3% for thrombocytopenia, 23.3% for nausea and appetite loss, and 6.7% for anemia, diarrhea, and renal dysfunction. Although all the patients had been hospitalized with a poor performance status with a giant tumor, 97% (29 of 30) could be discharged after the first cycle, resulting in an improvement in quality of life. CONCLUSION: Chemoradiotherapy could be a powerful regimen for controlling tumor progression in advanced gastric cancer, improving patients' quality of life with tolerable toxicity. A complete histologic response rate of >10% would be expected, even for large tumors with metastatic lesions.     

Phase II study of S-1 and irinotecan combination chemotherapy as a first-line therapy for patients with advanced gastric cancer. Korean Cancer Study Group Protocol ST05-02

Background:   Irinotecan plus intravenous 5-fluorouracil (5-FU) with leucovorin is effective against gastrointestinal cancer. S-1 is an oral fluoropyrimidine derivative and has a high response rate of about 40% for patients with advanced gastric cancer (AGC). We evaluated the antitumor activity and toxicities of an S-1 and irinotecan combination as a first-line therapy for patients with AGC.
Methods:   Patients with histologically confirmed unresectable or metastatic AGC were treated with S-1 40 mg/m² PO twice daily on days 1–14 and irinotecan 150 mg/m² i.v. on day 1 every 3 weeks until disease progression or unacceptable toxicities resulted.
Results:   A total of 45 patients were enrolled between September 2005 and March 2007. After a median of seven cycles of chemotherapy (range: 1–20, total: 350), 42 and 44 patients were evaluable for response and toxicity, respectively. On the intention-to-treat analysis, the overall response rate was 48.9% (95% C.I. 34.3–63.5%). The median time to progression was 5.7 months (95% C.I. 4.3–7.1) and the median overall survival was 10.4 months (95% C.I. 6.1–14.7). The commonly observed grade 3/4 adverse events were neutropenia (29.5% of patients) and vomiting (13.6%).
Conclusion:   An S-1 and irinotecan combination chemotherapy is active and tolerable as a first-line therapy for AGC.     

Phase I/II study of 3-week combination of S-1 and cisplatin chemotherapy for metastatic or recurrent gastric cancer

Purpose To define the maximum-tolerated dose (MTD) of S-1, given daily for 2 weeks followed by a 1-week rest, with a fixed dose of cisplatin on the initial day, and to determine the activity and safety of this regimen at the recommended dose (RD) when used as first line treatment of advanced gastric cancer (AGC). Patients and methods Cisplatin was fixed at a dose of 60 mg/m² on day 1 (D1) and the starting dose of S-1 was 60 mg/m²/day (30 mg/m² bid) (level I) on D1 to D14, every 3 weeks. The dose of S-1 was increased by 5 mg/m² bid up to 100 mg/m²/day (level V) unless the MTD was achieved. Results Sixty-two eligible patients were enrolled. MTD was set at level V with two of three patients developing grade 3 diarrhea or febrile neutropenia. The RD was determined at level IV (90 mg/m²/day). After the first 20 patients were enrolled in phase II, the protocol was amended; the S-1 dose was reduced to 80 mg/m²/day (N = 23) because of poor bone marrow recovery. The objective response was observed in 20 of 42 evaluable patients (48%). SD was achieved in 15 (36%). The median PFS was 5.3 months (95% CI, 4.6–6.0 months) with a median OS of 10.0 months (95% CI, 5.1–14.8 months). Grade 3–4 toxicities included neutropenia (33%), anemia (31%), and anorexia (24%). Conclusions The 3-week combination of cisplatin plus S-1 is active against AGC with favorable toxicitiy profiles. The phase II schedule or doses may need further refinements.     

替吉奥联合顺铂一线治疗晚期甲胎蛋白阳性胃癌的临床研究

目的：对比分析替吉奥联合顺铂一线治疗晚期早胎蛋白（AFP）阳性胃癌和晚期AFP 阴性胃癌的临床疗效。方法：回顾性收集郑州大学第一附属医院2010年1 月至2013年6 月符合纳入标准的晚期胃癌患者资料89例,根据治疗前血清AFP 水平分为AFP 阳性组（18例）和AFP 阴性组（71例）,对比分析两组接受替吉奥联合顺铂一线治疗的临床疗效。结果：AFP 阳性组与AFP 阴性组疾病缓解率（66.7% vs . 32.4% ,P = 0.028）、化疗后手术根治切除率（44.5% vs . 18.3% ,P = 0.029）比较差异具有统计学意义;AFP阳性组与AFP 阴性组化疗后未手术者中位无疾病进展期（7.5 m vs . 6.2 m ,P = 0.134）、中位总生存期（12.8 m vs . 10.7 m ,P = 0.144）比较差异均无统计学意义,然而化疗后手术根治切除的中位无病生存期（27.0 m vs . 15.6 m ,P = 0.034）比较有显著性差异;AFP 阳性组中位总生存期明显优于AFP 阴性组（16.0 m vs . 11.0 m ,P = 0.005）。 结论：晚期AFP 阳性胃癌患者更能从替吉奥联合顺铂的一线治疗中获益,延长生存期。     

Phase I study of S-1, docetaxel and cisplatin combination chemotherapy in patients with unresectable metastatic gastric cancer

The aim of this dose escalation study was to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs) and preliminary efficacy of docetaxel, S-1 and cisplatin combination chemotherapy in patients with unresectable metastatic gastric cancer. Seventeen patients received oral S-1 (40 mg m(-2) bid) on days 1-14, intravenous cisplatin (60 mg m(-2)) and docetaxel (60, 70 or 80 mg m(-2) depending on DLT) on day 8 every 3 weeks. The MTD of this combination was presumed to be docetaxel 70 mg m(-2). At this dose level, 40% of the patients (two of five) developed grade 4 neutropenia and 20% (one of five) exhibited grade 3 nausea during the first course. Therefore, the recommended dose of docetaxel was defined as 60 mg m(-2). The DLT was neutropenia. The response rate (RR) was 88.2% (15 of 17), consisting of one complete response and 14 partial responses. There were two stable diseases but no progressive disease. Of these 15 responders, four (23.5%) with high VEGF expression showed rapid tumour regression and achieved downstaging, leading to subsequent curative gastrectomy. Three of these have been disease free for about 3 years, suggesting a complete cure. In conclusion, this regimen was tolerable and showed a quite high RR, with an appreciable downstaging rate in metastatic gastric cancer.     

榄香烯口服乳联合替吉奥胶囊治疗老年晚期胃癌

目的:观察榄香烯口服乳联合替吉奥胶囊治疗老年晚期胃癌的客观疗效和毒副反应.方法:收集2012年5月至2015年5月本院肿瘤科收治的68例晚期胃癌患者,并随机分为两组,观察组34例,对照组34例.观察组给予替吉奥胶囊联合榄香烯口服乳治疗,对照组给予替吉奥胶囊.每例受试者至少2周期治疗后进行一次疗效评价,并评价患者的生活质量,记录患者出现的毒副反应.结果:观察组患者治疗的有效率为61.76%,明显高于对照组患者的44.12%,差异有统计学意义(P<0.05).观察组患者治疗后的生活质量明显优于对照组患者,差异具有统计学意义(P<0.05).观察组患者的消化道反应发生率和骨髓抑制发生率显著低于对照组,且无Ⅲ度以上毒副反应,差异具有统计学意义(P<0.05).结论:榄香烯口服乳联合替吉奥胶囊治疗老年晚期胃癌,能增加化疗有效率,且降低化疗毒副反应,患者获益显著.     

Phase I/II study of S-1 combined with weekly docetaxel in patients with metastatic gastric carcinoma

We designed a phase I/II trial of S-1 combined with weekly docetaxel to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate the efficacy and toxicity in metastatic gastric carcinoma (MGC). Patients with measurable disease received S-1 orally b.i.d. on days 1-14 and docetaxel intravenously on days 1 and 8 every 3 weeks. In phase I (n=30), each cohort received escalating doses of S-1 (30-45 mg m(-2) b.i.d.) and docetaxel (25-40 mg m(-2)); MTD was 45 mg m(-2) b.i.d. S-1/35 mg m(-2) docetaxel and RD was 40 mg m(-2) b.i.d. S-1/35 mg m(-2) docetaxel. Dose-limiting toxicities included grade 3 elevated liver enzymes, gastric perforation, grade 3 diarrhoea/fatigue, febrile neutropenia with grade 3 anorexia/fatigue, and neutropenic infection with grade 3 stomatitis/anorexia. In phase II (n=52), the overall response rate was 66.7% (95% confidence interval (CI): 53.8-79.6%) and the median time to progression and overall survival were 6.5 months (95% CI: 4.9-8.1) and 13.7 months (95% CI: 9.9-17.5), respectively. The most common grade 3/4 toxicity was neutropenia (29.4%), and febrile neutropenia/neutropenic infection occurred in 19.6% of patients. Non-haematological toxicities were generally mild. There was one treatment-related death due to pneumonitis. S-1 combined with weekly docetaxel is active in MGC with moderate toxicities.     

替吉奥为基础的化疗方案一线治疗晚期胃癌的Meta分析

目的:评价以替吉奥(S-1)为基础的化疗方案在晚期胃癌一线治疗中的疗效和不良反应.方法:通过中国知网、万方、EmBase及Pubmed数据库检索晚期胃癌一线接受以S-1为基础的化疗对比非S-1化疗方案的多中心随机对照研究(multicenter randomized clinical trial,mRCT),采用Rev...     

Analysis of the efficacy and safety of paclitaxel (albumin-bound) combined with S-1 and oxaliplatin combined with S-1 in the first-line treatment of advanced gastric cancer: a cohort study

BackgroundSingle-drug albumin-bound paclitaxel is one of the standard second-line treatments for advanced gastric cancer. Some clinical studies suggest that albumin-bound paclitaxel combined with S-1 can be used in the first-line treatment of gastric cancer. Both the two regimens have been commonly used in the past few years. Which is more effective? What’s the safety?MethodsFrom 2016 to 2021, a total of 70 untreated patients with advanced gastric cancer were included in our study. They all received at least two cycles of chemotherapy. Among them, 37 cases received standard S-1 and oxaliplatin (SOX) regimen, and 33 cases received albumin-bound paclitaxel combined with S-1 (aTS) regimen. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and adverse events (AEs) were analyzed. The OS and PFS curves were estimated using the Kaplan-Meier method.ResultsThe PFS of the aTS group was higher than that of the SOX group (9.27 vs. 7.03 months; P=0.046), but there was no significant difference in the OS between the two groups (19.2 vs. 12.5 months; P=0.131). The ORR of the aTS group was higher than that of the SOX group, and the side effects were tolerable.ConclusionsBoth regimens can be applied to advanced gastric cancer patients. Albumin-bound paclitaxel showed a higher ORR and could effectively prolong PFS.     

Phase II trial of cisplatin and gemcitabine in patients with advanced gastric cancer.

BACKGROUND: This phase II study was performed to determine the efficacy and toxicity of cisplatin and gemcitabine in patients with advanced gastric cancer. PATIENTS AND METHODS: Forty chemo-na?ve patients with measurable locoregionally advanced or metastatic gastric cancer were included; the median patient age was 53 years (range 35-71). Cisplatin was administered at a dose of 50 mg/m2, given in 1 h intravenously (i.v.) on days 1 and 8, followed after 24 h by gemcitabine at a dose of 800 mg/m2 given in 30 min i.v. on days 2, 9 and 16, every 28 days. RESULTS: A median number of four therapy cycles were given (range 2-8). Myelosuppresion was the most important toxicity. Grade 3-4 thrombopenia was observed in 19 patients (48%) and grade 3-4 leukopenia was observed in 23 (58%). Myelotoxicity was cumulative and caused omission of gemcitabine on day 16 in 55% of cycles. Non-haematological toxicity consisted mainly of grade 1-2 nausea and vomiting. Objective responses were observed in 30% of patients including two complete remissions and 10 partial remissions. Median survival was 11 months (range 3-27+). CONCLUSIONS: This cisplatin-gemcitabine regimen had moderate efficacy in patients with advanced gastric cancer, with manageable toxicity. Further studies with this combination may be warranted.     

Phase II trial of S-1 and concurrent radiotherapy in patients with locally advanced pancreatic cancer

Purpose  S-1 has a favorable effect in unresectable pancreatic cancer and a potential radiosensitizer. In addition, daily oral administration of S-1 is more convenient than continuous infusion of 5-fluorouracil. This study was designed to evaluate the efficacy and safety of S-1 and concurrent radiotherapy in patients with locally advanced pancreatic cancer. Methods  Eligibility criteria were histologically proven pancreatic adenocarcinoma, locally advanced disease, and no previous treatment. S-1 was administered orally at a dose of 40 mg/m² twice daily from day 1 to 14 and from day 22 to 35, and concurrent radiotherapy (a total dose of 50.4 Gy) was delivered in 28 fractions. One month after treatment completion, tumor response was evaluated by computed tomography (CT). Results  A total of 25 patients were evaluable for efficacy and toxicity on the basis of the intention-to-treat analysis. The response rate and disease control rate were 24.0 and 68.0%, respectively. There was no treatment-related death or grade 4 toxicity. The most common grade 3 hematologic and non-hematologic toxicities were thrombocytopenia (4.0%) and anorexia (20%), respectively. All toxicities were tolerable and transient. The median time-to-progression and median overall survival were 6.5 months (95% confidence interval, 4.1–9.0 months) and 12.9 months (95% confidence interval, 6.7–19.0 months), respectively, and the 1-year survival rate was estimated to be 43%. Conclusions  S-1 and concurrent radiotherapy shows favorable efficacy for disease control against locally advanced pancreatic cancer and was well tolerated with no severe toxicities.     

替吉奥联合奥沙利铂对比替吉奥联合顺铂方案一线治疗老年晚期胃癌的临床研究

目的 探讨替吉奥联合奥沙利铂方案（SOX）与替吉奥联合顺铂方案（SP）一线治疗老年晚期胃癌的疗效和毒副反应。方法 将56例老年晚期胃癌患者随机分为SOX组（n=30）和SP组（n=26）。SOX组：奥沙利铂130mg／m2 静滴,d1;替吉奥40～60mg／次口服,每天2次,d1～d14,21天为1周期。SP组：顺铂25mg／m2静滴,d1～d3;替吉奥用法同SOX组,21天为1周期。至少2个周期进行疗效评价。结果 SOX组和SP组的有效率分别为46.7％和38.5％（P=0.596）,疾病控制率分别为80.0％和76.9％（P=1.000）;中位无进展生存时间分别为6.0个月和5.6个月（P=0.831）,中位总生存时间分别为12.3个月和11.5个月（P=0.401）。SOX组和SP组的毒副反应均以血液学毒性为主,3～4级发生率的差异无统计学意义;非血液学毒性两组均为1～2级,SOX组以周围神经炎为主,SP组主要为恶心呕吐和肾功能异常。SOX组和SP组的KPS评分提高率分别为83.3％和46.2％（P=0.027）,FACT-G评分提高率分别为76.7％和38.5％（P=0.006）。结论 老年晚期胃癌患者可从替吉奥联合奥沙利铂方案或替吉奥联合顺铂方案一线治疗中获益,但替吉奥联合奥沙利铂方案的毒副反应更小,安全性更好。