经动脉持续灌注化疗治疗中晚期胰腺癌的临床分析

 目的 比较经动脉持续灌注化疗和全身静脉化疗治疗中晚期胰腺癌的临床疗效，探讨选择性动脉持续灌注化疗的临床应用价值。方法 51例中晚期胰腺癌，其中25例采用经动脉持续灌注吉西他滨和5-Fu方案，26例采用经外周静脉灌注吉西他滨和5-Fu方案。应用世界卫生组织实体瘤疗效评定标准评价疗效，肿瘤体积测量采用MRI或CT。使用临床受益反应（CBR）对疼痛、体力状况及体重改变情况作出综合评价。采用WH0抗肿瘤药物急性与亚急性毒性分级标准对不良反应进行评价。结果 动脉灌注化疗组的有效率（32．0％）高于外周静脉化疗组（23．1％），但差异无显著性。动脉灌注化疗组的临床受益率（80．0%）高于外周静脉化疗组（50．0％），差异有显著性。6个月、9个月、1年的累积生存率和中位生存时间，动脉灌注化疗组高于外周静脉化疗组，差异有显著性。按WHO分级标准，两组患者不良反应之间无显著性的差异。结论 经动脉持续灌注吉西他滨和5-Fu较外周静脉灌注吉西他滨和5-Fu能提高中晚期胰腺癌的临床受益率和生存期，其方法安全可靠，且不良反应少。     

动脉持续灌注化疗与静脉全身化疗治疗中晚期胰腺癌的疗效分析

Objective: To compare the curative effectiveness of continuous transarterial infusion chemotherapy and systemic venous chemotherapy in treating patients with advanced pancreatic cancer, and to evaluate the value of selective continu-ous transarterial infusion chemotherapy in treating advanced pancreatic cancer. Methods: Of the 51 patients with advanced pancreatic cancer receiving chemotherapy with gemcitabine and 5-fluorouracil, 25 patients were treated with selective con-tinuous transarterial infusion chemotherapy, 26 were treated with systemic venous chemotherapy, and curative effective-ness was analyzed retrospectively. Curative effectiveness included tumor volume, clinical benefit response (CBR), acute and subacute toxic reactions of antitumor drugs, survival rate and median survival time. Results: The objective effective rate in transarterial group was 32.0% versus 23.1% in systemic group without any significant difference (P = 0.475). Clinical benefit rates in transarterial group and systemic group were 80.0% and 50.0% respectively (P = 0.025). The 6-, 9-and 12-month accumulated survival rates and median survival time in transarterial group were higher than those of the systemic group (P = 0.002), the differences were statistically significant. However, the adverse reactions between the two groups were not statistically significant. Conclusion: Compared with systemic chemotherapy, continuous transarterial infusion chemotherapy with gemcitabine and 5-fluorouracil could improve clinical benefit rate and survival time of patients with advanced pancreatic cancer, it is safe and reliable, and the adverse reactions is less.     

动脉持续灌注化疗与静脉全身化疗治疗中晚期胰腺癌的疗效分析

Objective: To compare the curative effectiveness of continuous transarterial infusion chemotherapy and systemic venous chemotherapy in treating patients with advanced pancreatic cancer, and to evaluate the value of selective continuous transarterial infusion chemotherapy in treating advanced pancreatic cancer. Methods: Of the 51 patients with advanced pancreatic cancer receiving chemotherapy with gemcitabine and 5-fluorouracil, 25 patients were treated with selective continuous transarterial infusion chemotherapy, 26 were treated with systemic venous chemotherapy, and curative effectiveness was analyzed retrospectively. Curative effectiveness included tumor volume, clinical benefit response (CBR), acute and subacute toxic reactions of antitumor drugs, survival rate and median survival time. Results: The objective effective rate in transarterial group was 32.0% versus 23.1% in systemic group without any significant difference (P = 0.475). Clinical benefit rates in transarterial group and systemic group were 80.0% and 50.0% respectively (P = 0.025). The 6-, 9- and 12-month accumulated survival rates and median survival time in transarterial group were higher than those of the systemic group (P = 0.002), the differences were statistically significant. However, the adverse reactions between the two groups were not statistically significant. Conclusion: Compared with systemic chemotherapy, continuous transarterial infusion chemotherapy with gemcitabine and 5-fluorouracil could improve clinical benefit rate and survival time of patients with advanced pancreatic cancer, it is safe and reliable, and the adverse reactions is less.     

GP方案区域化疗与静脉化疗治疗进展期胰腺癌疗效的对比研究

目的:对比分析采用GP方案胰腺区域性动脉灌注与静脉化疗治疗晚期胰腺癌的临床疗效。方法:采用随机法将68例晚期胰腺癌分为胰腺区域性动脉灌注组36例和静脉化疗组32例,平均化疗2.5个周期。结果:胰腺区域性动脉灌注组有效率为25.0%,中位疾病进展时间为9个月,临床获益率为50.0%,中位生存期为12个月,6个月生存率为55.6%,9个月生存率为25.0%;静脉化疗组有效率为12.5%,中位进展时间为3个月,中位生存期为5.5个月,临床获益率为25.0%,6个月生存率为31.2%,9个月生存率为18.7%。胰腺区域性动脉灌注组有效率、临床获益率、中位进展时间、中位生存期及生存率均高于静脉化疗组,差异有统计学意义,P<0.05。胰腺区域性动脉灌注组白细胞及血小板减少发生率分别为27.8%和25.0%,静脉化疗组分别为71.9%和56.3%。两组比较差异均有统计学意义,χ2值分别为13.189和6.911,P值分别为0.000和0.009。结论:GP方案胰腺区域性动脉灌注是治疗进展期胰腺癌的有效方案,且毒副反应可耐受。     

经动脉灌注吉西他滨和5-氟尿嘧啶联合热疗治疗中晚期胰腺癌的临床分析

目的：探讨经动脉灌注吉西他滨（Gemcitabine，商品名健择）和5-氟尿嘧啶（5-FU）联合内生场热疗治疗中晚期胰腺癌的临床疗效。方法：18例中晚期胰腺癌患者，采用改良Seldinger技术，动脉插管后选择性置管于胰腺癌的供血动脉，灌注吉西他滨1000mg／m^2；之后行内生场热疗，热疗同时经动脉留置导管灌注卡铂400mg／m^2；热疗后，用输液泵经动脉留置管灌注5-FU 1g，连用2d。随访观察客观疗效、临床受益反应、患者的生存期及不良反应等。结果：18例患者的客观缓解率为22．20％，临床受益反应为44．40％，Kaplan-Meier法计算6、9和12个月的累积生存率分别为83．33％、66．67％和33．33％，频数分布法计算中位生存期为11个月。结论：经动脉灌注吉西他滨和5-FU联合内生场热疗治疗中晚期胰腺癌可获得较好的临床疗效，患者耐受良好，值得进一步研究。     

Phase II evaluation of continuous-infusion 5-fluorouracil, leucovorin, mitomycin-C, and oral dipyridamole in advanced measurable pancreatic cancer: a North Central Cancer Treatment Group Trial

At present there remains a need for more effective systemic therapy in advanced pancreatic cancer. Some studies have suggested that infusional chemotherapy schedules and biomodulation of 5-fluorouracil (5-FU) may improve the therapeutic outcome in advanced colon cancer. One such regimen that uses continuous infusion 5-FU, weekly leucovorin, daily dipyridamole, and intermittent mitomycin-C has activity in both colon and unresectable pancreatic carcinoma. The intent of this trial was to test the effectiveness of this four-drug regimen in advanced pancreatic cancer. Patients received 5-FU 200 mg/m2 daily by continuous infusion, leucovorin 30 mg/m2 IV weekly, mitomycin-C 10 mg/m2 day 1, and dipyridamole 75 mg orally four times daily for 5 weeks. After a 1-week break, treatment cycles were repeated every 6 weeks. Eligibility included biopsy-proven advanced measurable pancreatic cancer, Eastern Cooperative Oncology Group performance status 0 and 2, and no prior systemic chemotherapy. Of 46 evaluable patients, 9 partial responses and 1 complete tumor response were seen, for an overall response rate of 22% (95% confidence interval 11-36%). The median survival in the group of 50 patients registered to this trial was 4.6 months, with a range of 0.33 to 40.2 months. Toxicity was manageable, with the most common toxicities (> or =grade III National Cancer Institute Common Toxicity Criteria) being anorexia (13%), stomatitis (17%), and hand-foot syndrome (13%). Of note, little severe hematologic toxicity and no significant headaches were reported. Although some patients did respond, the therapeutic results are not encouraging enough to take this regimen to phase III testing.     

经动脉灌注健择化疗联合三维适形放射治疗局部晚期胰腺癌的临床研究

Objective： To evaluate the clinical effect of transarterial infusion chemotherapy of gemcitabine plus three dimensional conformal radiotherapy on patients with local advanced pancreatic cancer. Methods： Fifty-one patients with local advanced pancreatic cancer from June 2002 to February 2004 were enrolled, twenty-four patients of combined group were treated with transarterial infusion chemotherapy of gemcitabine plus three dimensional conformal radiotherapy, while twenty-seven patients of control group were treated only with transarterial infusion chemotherapy of gemcitabine. Results： There were significant statistical differences between two groups in clinical benefit response （91.7% versus 74.1%, P 〈 0.01） and overall remission rate （70.8% versus 33.3%, P 〈 0.01）. The 6-month survival rate, 12-month survival rate and 24-month survival rate of combined group were 83.3%, 62.5% and 37.5% respectively, while that of control group were 55.6%, 33.3% and 11.1% respectively. This showed significant difference between the two groups. Conclusion： Transarterial infusion chemotherapy of gemcitabine plus three dimensional conformal radiotherapy may be better than single transarterial infusion chemotherapy of gemcitabine in improving survival rates and elongating survival time of patients with local advanced pancreatic cancer.     

Phase I study to evaluate multiple regimens of intravenous 5-fluorouracil administered in combination with weekly gemcitabine in patients with advanced solid tumors: a potential broadly active regimen for advanced solid tumor malignancies.

BACKGROUND: The purpose of this study was to determine the maximum tolerated dose and toxicity profile of gemcitabine given on a weekly schedule with continuous infusion 5-fluorouracil. PATIENTS AND METHODS: Eligible patients with advanced solid tumors received escalating doses of gemcitabine 200 and 300 mg/m(2) weekly as a 30-minute infusion on Days 1, 8, and 15 every 4 weeks (schedule 1) or 450, 600, 800, 1000, 1250, 1500, 1800, and 2200 mg/m(2) on Days 1 and 8 (schedule 2) every 3 weeks, respectively. At the completion of gemcitabine infusion (Day 1), patients received fixed dose continuous infusion of 5-fluorouracil at either 300 mg/m(2) (Days 1-21) or 200 mg/m(2) (Days 1-21; schedule 1) every 4 weeks or 200 mg/m(2) (Days 1-14; schedule 2] every 3 weeks, respectively. Toxicity assessments were performed weekly on study, and efficacy measurements were performed every 6-8 weeks. RESULTS: Seventy patients with advanced solid malignancies received a total of 220 cycles of combination chemotherapy. Eleven (14.3%) patients received no more than 1 treatment cycle of combination therapy. Schedule 1 maximum tolerated dose of gemcitabine was 600 mg/m(2)/week when combined with 5-fluorouracil (5-FU) at 200 mg/m(2)/day (Days 1-21) repeated every 4 weeks. The schedule 2 maximum tolerated dose of gemcitabine was 2200 mg/m(2)/week when combined with 5-FU dosed at 200 mg/m(2)/day (Days 1-14) repeated every 3 weeks. In schedule 1, the limiting factor for gemcitabine delivery was the Day 15 dose that often was omitted because of myelosuppression and/or mucositis. In schedule 1 cycle 1, nonhematologic toxicity was common and included Grade 3-4 toxicities: mucositis (8 patients), fatigue (2 patients), and anorexia (1 patient). One patient had Grade 3-4 neutropenia at dose level 5 (maximum tolerated dose). In schedule 2 cycle 1, hematologic toxicities were more common than nonhematologic toxicity and included Grade 3 anemia (3 patients), Grade 3 neutropenia (4 patients), and Grade 3 thrombocytopenia (2 patients). The nonhematologic toxicities included Grade 3 mucositis (3 patients), Grade 3 fatigue (2 patients), and Grade 3 dehydration (1 patient). Overall, antitumor activity was observed in seven patients. Three of 30 patients with cytokine refractory renal cell carcinoma (RCC; relative risk [RR] 10 %; 95% confidence interval [CI], 0.82-22%) had a partial response. Of the remaining 27 patients with RCC, 4 patients had a minor response, and 10 patients had stable disease lasting a median of 6.4 (range, 4-12) months. The remaining 5 responses occurred in 40 patients (RR, 12.5%; 95% CI, 4.2-26.8%): 2 patients with 5-FU refractory colon carcinoma, 1 patient with hepatoma, 1 patient with paclitaxel-cisplatin-resistant ovarian carcinoma, and 1 patient with cisplatin-resistant head and neck squamous cell carcinoma had a partial response. CONCLUSIONS: For Phase II development, gemcitabine 450-600 mg/m(2) on Days 1, 8, and 15 can be safely combined with 5-FU 200 mg/m(2) given as a continuous infusion (Days 1-21) of a 28-day cycle or gemcitabine 1800 mg/m(2) Days 1 and 8 given with 5-FU 200 mg/m(2) as a continuous infusion (Days 1-14) of a 21-day cycle. The observed antitumor activity in several solid tumors, especially in renal cell carcinoma, warrants broad Phase II evaluation.     

A phase II study of mitomycin C, cisplatin and protracted infusional 5-fluorouracil in advanced pancreatic carcinoma: efficacy and low toxicity.

BACKGROUND: The effective treatment of unresectable pancreatic carcinoma represents a formidable challenge. There is a need to develop systemic therapies which combine efficacy with acceptable toxicity. The current 'gold standard' gemcitabine gives an objective response rate of the order of 20% and median survival up to 6 months. Here we have evaluated the efficacy and toxicity of mitomycin C, cisplatin and protracted infusional 5-fluorouracil (MCF). PATIENTS AND METHODS: Forty-five patients with locally advanced (13 patients) or metastatic (32 patients) pancreatic carcinoma were treated with mitomycin C 7 mg/m(2) 6 weekly, cisplatin 60 mg/m(2) 3 weekly and protracted venous infusion 5-FU 300 mg/m(2)/day. Patients were evaluated for response after three cycles and received six cycles in total in the absence of progressive disease or poor tolerance. Median age was 62 (45-75) years; 41 patients were World Health Organization performance status 0-1. RESULTS: Treatment was well tolerated with 36 (84%) patients completing three or more cycles. Grade 3 or 4 toxicities were uncommon: anaemia in three patients (7%), mucositis in two (5%), nausea and vomiting in three (7%) and diarrhoea in one (1%). An objective response was seen in 21 (46%) patients. There was one complete response. The median survival overall was 7.1 months and 10.5 months in responders. The median duration of response was 4.3 months. One-year survival was 29%, 2-year survival was 18%. CONCLUSIONS: MCF combines efficacy with low toxicity in the treatment of advanced pancreatic carcinoma. The efficacy is at least comparable and may be superior to single-agent gemcitabine and MCF may therefore provide a cost-effective alternative.     

选择性动脉插管持续灌注化疗治疗晚期胰腺癌的疗效分析

背景与目的：晚期胰腺癌化学治疗效果差。本研究目的是探讨选择性动脉插管持续灌注化疗治疗晚期胰腺癌的临床疗效与应用价值。方法：20例晚期胰腺癌经选择性动脉插管持续灌注化疗。采用Seldinger技术经股动脉插管留置导管12例,经左锁骨下动脉插管植入药盒导管系统8例。导管选择至肿瘤供血动脉持续灌注化疗药物。9例采用THP-ADM HCPT 5-FU／CF方案,11例采用GEM CBP 5-FU／CF方案,4天为一疗程。4～6周重复1次疗程。治疗后观察客观缓解率、临床受益疗效(CBR)和病人的生存时间。结果：客观缓解率10％(CR、PR各1例),临床受益疗效70．0％,6个月及9个月生存率分别为58．8％和39．2％,中位生存期8．8个月。无出现插管合并症。结论：选择性动脉插管持续灌注化疗治疗晚期胰腺癌安全可靠。临床受益疗效良好,可提高患者的生存质量和生存期。值得临床进一步观察研究。     

Gemcitabine in advanced pancreatic cancer: a phase II trial

The 5-year survival for pancreatic cancer is usually less than 5%, and no treatment has demonstrated consistent effect on patient survival and disease-related symptoms. Early studies with gemcitabine suggested a modest antitumor activity with significant improvement in disease-related symptoms. This phase II study reports the activity of gemcitabine on 33 consecutive patients with unresectable pancreatic carcinoma. Twenty-three patients had metastatic and 10 locally advanced unresectable disease. Twenty-six patients had not received any previous treatment and seven had received first-line chemotherapy with 5-fluorouracil. Gemcitabine 1,000 mg/m2 was administered intravenously in 30 minutes in the first cycle once weekly for up to 7 weeks followed by 1 week rest; then in subsequent cycles, once weekly for 3 of every 4-week cycle. Four patients obtained partial response (12%). Fifteen patients (45%) had stable disease with a median duration of 32 weeks (range: 16-75 weeks), and 14 patients experienced progressive disease. Median duration of response was 34.5 weeks (range: 19-50 weeks). Median survival was 33 weeks (range: 2-91 weeks). All 4 responding patients and 14 of 15 (93%) patients with stable disease had improvement in performance status and decrease in daily analgesic requirement. Toxicity was mild and mainly consisted of moderate and rapidly reversible myelosuppression. We conclude that gemcitabine chemotherapy was very well tolerated and determined a significant clinical improvement with modest antitumoral activity in patients with advanced pancreatic cancer.     

吉西他滨治疗14例晚期胰腺癌

目的：研究吉西他滨（gemcitabine)治疗晚期胰腺癌的疗效。方法：14例进行展期胰腺癌患者,用吉西他滨第1周800mg/m^2,第2周1000mg/m^2,第3周1200mg/m^2,每周1次,每次以0．9％生理盐水100ml溶解后静脉滴注,30分钟滴完,连续3周,随后休息1周为一疗程。以后每4周重复一次,共6个疗程。结果：疼痛缓解有效率为64％（9／14）,处长了中位生存期,平均为8．7个月。临床受益反应为43％。吉西他滨治疗晚期胰腺癌能显著改善晚期胰腺癌患者的临床症状,减轻疼痛。生活质量有明显提高。结论：吉西他滨可作为晚期胰腺癌综合治疗时首选的化疗药物。     

PF方案化疗同步放射治疗局部中晚期鼻咽癌的5年疗效分析

目的:探讨用PF方案同期化疗联合放射治疗局部中晚期鼻咽癌5年疗效.方法:52例局部中晚期鼻咽癌患者,在放疗第1、5周联合PF方案化疗,DDP70 mg/㎡,d1,静脉滴入;5-FU 500 mg/㎡,d2起96 h静脉灌注,共2个周期.另配对选取同时期52例单纯放疗者为时照组,两组放疗方法和剂量相似.结果:治疗结束后3...     

区域动脉灌注健择及5-Fu对胰腺癌术后复发及预后的影响

目的　探讨胰腺癌术后区域动脉灌注健择及 5 Fu对其复发及预后的影响。方法　对 17例胰腺癌病人术后行预防性区域动脉灌注健择及 5 Fu ,每 4周一次 ,观察病人的疗效 (治疗组 )。并与 2 3例单纯手术切除患者的生存及复发时间作对比 (观察组 )。结果　治疗组 1,2 ,3年生存率为 88 2 % ,70 6% ,5 8 8%。而 1,2 ,3年复发率为 (包括肝脏及骨转移 ) 17 7% ,2 9 4% ,47 1%。单纯手术组的 1,2 ,3年生存率为 65 2 % ,47 8% ,2 1 7%。 1,2 ,3年复发率为 2 1 7% ,60 9% ,69 6%。 3年生存率及复发率相比差异具有显著性 (P <0 0 1)。结论　胰腺癌术后辅以区域动脉灌注健择及 5 Fu可能是改善预后提高生存率的有效手段。     

奥沙利铂联合亚叶酸钙和氟尿嘧啶方案治疗老年人胃肠道肿瘤临床观察

 目的 观察奥沙利铂（L-OHP，商品名：艾恒）联合亚叶酸钙（CF）和氟尿嘧啶（5-Fu）即改良FOLFOX方案治疗老年人胃肠道肿瘤的疗效和毒性反应。方法 34例老年人胃肠道肿瘤，其中胃癌15例，大肠癌19例。给予改良FOLFOX方案，L-OHP 130 mg／m2静脉滴注4 h，第1天；CF 200 mg／m2静脉滴注2 h，第1 ~ 5天；5-Fu 500 mg／m2静脉滴注，第1 ~ 5天。每3周1个疗程，至少用3个疗程。结果 全组患者总有效（CR+PR）率44.1 %，其中胃癌总有效率40.0 %，大肠癌总有效率47.4 %，两组比较差异无统计学意义（P＞0.05）。中位缓解时间8.6个月，中位生存期11.2个月，1 年生存率52.2 %。主要毒副反应为白细胞减少，感觉神经毒性。结论 改良FOLFOX方案治疗老年人胃肠道肿瘤有效率较高，毒副反应轻。     

A Phase I trial of arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for unresectable advanced pancreatic cancer after vascular supply distribution via superselective embolization

Background: We previously reported that arterial infusion chemotherapy improvedthe response rate and survival of the patients with pancreaticcancer at advanced stages in an open trial. We conducted a PhaseI trial of arterial infusion chemotherapy with gemcitabine and5-fluorouracil for advanced pancreatic cancer after vascularsupply distribution via superselective embolization. Methods: Patients were treated after arterial embolization for hemodynamicchange to restrict the blood flow into the pancreas (mainlyto the great pancreatic artery and the caudal pancreatic artery).Arterial infusion chemotherapy consisted of gemcitabine in dosesthat were increased from 600 to 1000 mg/m² in subsequent cohortson Day 1 plus continuous infusion of 5-fluorouracil 300 mg/m²/dayon Days 1–5 every 2 weeks. Result: Twelve patients were enrolled. The maximum tolerated dose ofgemcitabine was determined to be Level 3 (1000 mg/m²). Onlyvery mild hematological and non-hematological toxicities werenoted. The overall response rate was 33.3%. The median survivaltime was 22.7 (95% CI; 9.5–24.5) months and the 1- and2-year overall survival rates were 83.3 and 25.0%, respectively. Conclusion: Arterial infusion chemotherapy using 1000 mg/m² gemcitabineon Day 1 and 300 mg/m²/day 5-fluorouracil on Days 1–5every 2 weeks warrants a Phase II study.     

三维适形放疗同步奥沙利铂联合吉西他滨化疗治疗局部晚期胰腺癌的临床观察

目的 探讨三维适形放疗(3DCRT)同步奥沙利铂联合吉西他滨化疗治疗局部晚期胰腺癌的疗效和毒副反应.方法 入组局部晚期胰腺癌30例均接受3DCRT,总剂量45.0～50.4 Gy,5～6周内完成.在放疗的同时接受化疗,放疗结束后继续化疗2～4个周期,方案为:奥沙利铂100mg/m2,静脉滴注,d1;吉西他滨1 000 ...     

Phase I chemotherapy study of biochemical modulation of folinic acid and fluorouracil by gemcitabine in patients with solid tumor malignancies.

PURPOSE: This phase I biochemical modulation study evaluated the maximum-tolerated dose (MTD), toxicity, and effectiveness of the combination of folinic acid (FA)/fluorouracil (5-FU) followed by escalated dose levels of gemcitabine (FFG) in patients with advanced solid tumors. PATIENTS AND METHODS: Patients were refractory to primary treatment and/or without effective treatment options. Twenty-eight patients received an intravenous (IV) infusion of FA 100 mg/m(2) over 1 hour and a 5-FU 450 mg/m(2) IV bolus in the middle of the FA infusion. After the FA infusion, gemcitabine was administered at a steady rate of infusion of 10 mg/m(2)/min over initially 30 minutes and with increases of an additional 15 minutes at each given level. One cycle consisted of six weekly treatments followed by a 2-week rest. RESULTS: The MTD of gemcitabine was established at 900 mg/m(2) given over 90 minutes. Eight patients of 21 with metastatic colorectal cancer achieved responses (one complete response; seven partial responses), for a response rate of 38%. Responses were seen across the gemcitabine doses of 300 to 900 mg/m(2). One patient had prior treatment with FA/5-FU for advanced disease. Patients with colorectal carcinoma had a median survival of 18 months, and the patient with lung carcinoma has been alive for 24+ months. CONCLUSION: The combination chemotherapy of FFG was well tolerated and may benefit patients with advanced colorectal carcinoma. A phase II evaluation in this patient population is in progress.     

Phase II study of gemcitabine combined with uracil-tegafur in metastatic pancreatic cancer

OBJECTIVE: The single agent gemcitabine is the standard first-line treatment for advanced pancreatic cancer. Recent studies of a combination of gemcitabine and 5-fluorouracil (5-FU) revealed that survival data were superior to those with gemcitabine or 5-FU alone. The administration of oral uracil-tegafur (UFT) is more convenient and simulates the effect of a continuous or protracted infusion of 5-FU. Therefore, we conducted a phase II study of gemcitabine combined with UFT in metastatic pancreatic cancer patients and assessed the efficacy and the toxicity of the regimen. METHODS: Twenty-two pancreatic adenocarcinoma patients (18 males, 4 females) were enrolled from December 2000 to September 2002. The regimen consisted of gemcitabine 1,000 mg/m(2) once weekly for 3 consecutive weeks, and oral UFT 390 mg/m(2)/day (in 3 divided doses) on days 1-14. The cycle was repeated every 28 days. The objective tumor response was evaluated after 2 courses of chemotherapy. RESULTS: 82 cycles were administered in total, with a median of 3 cycles per patient (range 1-6 cycles). The median age was 52 years (range 28-69 years). Response to treatment could be assessed in all patients. The objective response rate was 22.7% (95% CI, 7.8-45.4) with no complete response and 5 partial responses. Four patients (18.2%) had stable disease and 13 patients (59.1%) had a progression. The median time to progression was 4.2 months (range 0.9-13.6). The median overall survival was 5.8 months (range 0.5-13.6). Of 10 patients eligible for the assessment of clinical benefit response, 4 (40%, 95% CI 12.2-73.8) showed clinical benefit. Among 21 patients with baseline CA 19-9 levels, CA 19-9 was reduced by 50% or more in 12 patients (57.1%). The chemotherapy was generally well tolerated and the most common grade 3-4 toxic side effects were neutropenia (18.2%), anemia (4.5%), and diarrhea (4.5%). CONCLUSIONS: The combination chemotherapy with gemcitabine and UFT in metastatic pancreatic cancer was tolerable for most patients but showed modest response rates and clinical benefit. However, a randomized phase III study should be conducted in order to further test the efficacy of the regimen.     

Capecitabine and radiation therapy preceded and followed by combination chemotherapy in advanced pancreatic cancer

PURPOSE: The primary objective of this study was to evaluate the tolerance and toxicity of radiation therapy (RT) and capecitabine in patients with advanced, unresectable pancreatic carcinoma. To control micrometastatic disease, combination chemotherapy (gemcitabine and cisplatin) before and after combined modality therapy (CMT) was planned. METHODS AND MATERIALS: Patients with unresectable or metastatic pancreatic cancer were eligible. Gemcitabine 1000 mg/m2 and cisplatin 35 mg/m2 were administered on Days 1 and 8 of a 21-day cycle for two cycles. RT was then given to a dose of 50.4 Gy in 1.8 Gy fractions. Patients were treated with capecitabine 1330 mg/m2 daily during RT. After CMT, two additional cycles of gemcitabine and cisplatin completed the treatment. RESULTS: Twenty-three patients were treated. Eighteen patients completed CMT. One patient was removed from study during CMT for toxicity issues. Treatment delays and dose reductions were common during the final two cycles of gemcitabine and cisplatin as a result of myelosuppression. Median survival was 10.1 months (95% confidence interval [CI] = 7.6, 13.7) for all 23 patients and 12.8 months (95% CI = 8.2, 18.9) for 18 patients without metastasis. CONCLUSION: Combined modality therapy with RT and capecitabine was well tolerated. Chemotherapy after CMT was difficult to complete owing to cumulative myelosuppression. Survival, response, and toxicity were comparable to infusional 5-fluorouracil and RT.