5-氟尿嘧啶节律性化疗对晚期胃癌患者的临床疗效观察

目的观察5-氟尿嘧啶节律性化疗对晚期胃癌患者的临床疗效。方法选择我院24例晚期胃癌患者,使用5-氟尿嘧啶500 mg静脉持续泵入12 h d1-21,4周1个疗程,3～9个疗程后,对接受至少3个疗程的患者进行疗效评价。结果 24例患者随访8～24个月,3例部分缓解(12.5%),9例病情稳定(37.5%),无1例患者完全缓解,12例患者病情进展(50.0%),疾病控制率为50.0%。治疗有效患者的中位疾病进展时间(TTP)为3.2个月。结论 5-氟尿嘧啶节律性化疗可以有效控制老年晚期胃癌患者的病情进展,不良反应少且轻。     

A phase II study of combination chemotherapy with gemcitabine, 5-fluorouracil, and cisplatin for advanced pancreatic cancer]

BACKGROUND/AIMS: Gemcitabine has been the standard regimen for advanced pancreatic cancer, but the effect on the response rate and survival is still disappointing, leading to many trials of combination chemotherapy. 5-FU and cisplatin were combined with gemcitabine in this trial, as they are synergistic with gemcitabine and each other as well. This study was aimed to assess the effectiveness and safety of combination chemotherapy with gemcitabine, 5-FU, and cisplatin for advanced pancreatic cancer. METHODS: Patients with advanced pancreatic cancer were entered into this study. Gemcitabine at a dose of 800 mg/m2 on day 1 and 8, 5-FU 1,000 mg/m2/day from day 1 to 3 for 72 hours, and cisplatin 60 mg/m2 on day 2, 24 hours after the start of gemcitabine were administered every 3 weeks. RESULTS: From December 2001 to January 2004, twenty patients were enrolled in this study. Among 17 of these patients assessable, 3 patients had a partial remission with the response rate of 23.6% (95% confidence interval, 6.2-41.0%). The median time to disease progression was 230 days and median duration of survival was 322 days. Among total of 91 cycles, leukopenia, neutropenia, and thrombocytopenia of grade 3 or 4 occurred in 12 cycles (13.2%), 12 cycles (13.2%), and 23 cycles (24.4%), respectively. Grade 3 or 4 mucositis developed at 2 cycles (2.2%), and nausea and vomiting were encountered in 3 cycles (3.3%). CONCLUSIONS: Combination chemotherapy with gemcitabine, 5-FU, and cisplatin for advanced pancreatic cancer is active and well-tolerated, warranting a phase III study.     

The clinical efficacy of adjuvant systemic chemotherapy with gemcitabine and NSC-631570 in advanced pancreatic cancer

BACKGROUND/AIMS: Recently we have shown that NSC-631570 (Ukrain) is a safe and effective drug in the treatment of unresectable pancreatic cancer. The aim of this study was to determine the effectiveness of the combined treatment with Gemcitabine and NSC-631570 in the adjuvant treatment of resected advanced pancreatic cancer. METHODOLOGY: 30 patients received adjuvant chemotherapy following surgical resection for pancreatic cancer. Chemotherapy consisted of Gemcitabine according to the Burris-protocol with weekly infusions of 1000 mg/sqm. Immediately following Gemcitabine infusion 20mg of NSC-631570 were administered intravenously over 15 minutes. RESULTS: WHO grade II toxicities were observed in 53%, no WHO grade III or IV toxicities occurred. In 80% of the patients recurrence of the disease was observed. The relapse-free survival time was 21.7 months. The actuarial survival rates were 86.7% after one year, 76.6% after two years, 46.7% after three years and 23.3% after five years. The median survival time according to Kaplan-Meier regression analysis was 33.8 months. CONCLUSIONS: Adjuvant chemotherapy in advanced stages of pancreatic cancer using the combination of Gemcitabine and NSC-631570 is a safe treatment and seems to lead to a prolonged survival. Although further investigation is needed to confirm these results, the combined treatment of Gemcitabine and NSC-631570 is a promising therapy for the adjuvant treatment of resectable advanced pancreatic cancer.     

老年晚期胰腺癌患者对吉西他滨联合顺铂化疗耐受性分析

目的 探讨老年晚期胰腺癌患者对吉西他滨联合顺铂化疗的耐受性.方法 对2004年1月至2009年1月收治的34例老年(>70岁)晚期胰腺癌患者的临床资料进行回顾性分析.结果 34例患者均行吉西他滨联合顺铂化疗,其中6例获得部分缓解(partial remission,PR),16例疾病稳定(stable disease,SD),临床获益率64.7%.18例患者治疗后镇痛药物用量减少≥50%,疼痛强度VAS评分下降35%以上;22例患者体力状况明显提高,体重增加≥7%.恶心、呕吐发生率为38.2%(13/34),4例巩膜皮肤黄染加重,肝功能异常,化疗2个周期中断治疗.Ⅲ～Ⅳ度骨髓抑制的发生率为34.6%,白细胞、血红蛋白、血小板均有不同程度的下降.血小板减少率28.3%(12/34),应用G-CSF治疗后血常规可恢复正常.无外周神经毒性发生,无化疗相关死亡.结论 老年胰腺癌,行为状态良好者可耐受吉西他滨联合顺铂方案化疗.     

Results of a retrospective analysis of gemcitabine as a second-line treatment after chemoradiotherapy and maintenance chemotherapy using 5-fluorouracil in patients with locally advanced pancreatic cancer

Background  Many studies of concurrent chemoradiation therapy with 5-fluorouracil (5-FU) for locally advanced pancreatic cancer have been reported with a median survival time of approximately 10 months. Recently, gemcitabine (GEM) has been administered immediately after chemoradiation. The clinical outcome of chemoradiation therapy in conjunction with 5-FU and second-line chemotherapy with GEM after disease progression has not been clarified. Methods  Patients with locally advanced pancreatic cancer were treated with concurrent radiation therapy (1.8 Gy/fraction; total dose, 50.4 Gy) with 5-FU (200 mg/m² every day) until disease progression, followed by GEM (1000 mg/m², days 1, 8, 15, and every 4 weeks) as second-line therapy. Results  Of the 18 patients with locally advanced pancreatic cancer who received chemoradiation therapy with 5-FU, there were three partial responses, giving a response rate of 17%. The median time to progression was 170 days. The median survival time was 443 days. During chemoradiation therapy, the incidences of grade 3 or 4 anorexia, nausea, mucositis, and gastric ulcer were 33%, 22%, 17%, and 17%, respectively. Sixteen patients received second-line chemotherapy with GEM, of whom one patient had a partial response. The median time to progression from the initiation of GEM was 113 days, and median overall survival time was 231 days. Major toxicities were hematological toxicities: grade 3 or 4 leukopenia in 75% and anemia in 31%. Conclusions  The treatment strategy with concurrent chemoradiation and maintenance chemotherapy with 5-FU followed by second-line chemotherapy with GEM may be an option for locally advanced pancreatic cancer.     

Phase I-II trial of weekly gemcitabine plus high-dose 5-fluorouracil and leucovorin in advanced pancreatic cancer

BACKGROUND: Pancreatic cancer is a dismal disease. Few drugs, including gemcitabine and 5-fluorouracil (5-FU), have notable antitumor effects against advanced pancreatic cancer. The purpose of the present study was to determine the maximum tolerated dose (MTD) of 5-FU and the efficacy and toxicity profile of weekly gemcitabine plus infusional 5-FU/leucovorin in advanced pancreatic cancer. METHODS: Patients with histo-/cytologically confirmed, advanced pancreatic cancer were eligible. Treatment consisted of a 30-min infusion of gemcitabine (800 mg/m2), followed by a 24-h infusion of 5-FU and leucovorin (300 mg/m2) at day 1, day 8 and day 15 every 28 days, and was termed the GemFL24 regimen. The dose of 5-FU was escalated from 1600, 2000, to 2600 mg/m2 in the phase I study, and fixed MTD for subsequent enrolled patients. RESULTS: Eighteen patients were enrolled in the phase I study, and 24 in phase II. The MTD of 5-FU was 2000 mg/m2, with major dose-limiting toxicities being febrile neutropenia and delayed recovery from neutropenia. The dose intensity of gemcitabine of the 35 patients with 5-FU dosage set at MTD was 593 mg/m2 per week. In the entire series of 42 patients, myelosuppression was the main toxicity, with grade 3 neutropenia in eight patients, and grade 3/4 thrombocytopenia in six. On an intention-to-treat analysis, the overall and clinical benefit response rates were 22% and 46%, respectively; with median progression-free and overall survival of 4.1 and 6.9 months, respectively. CONCLUSIONS: The GemFL24 regimen is a feasible and moderately active treatment with manageable toxicities for advanced pancreatic cancer, and could be a basis for further combination with other anticancer drugs.     

Randomized comparative study of surgical adjuvant chemotherapy using 5-fluorouracil and dl-leucovorin with CDDP, 5-FU and dl-leucovorin for advanced colorectal cancer

BACKGROUND: 5-fluorouracil (5-FU) is the most useful chemotherapeutic agent for colorectal carcinoma. Recently, the effectiveness of multidrug therapy in modifying the anticancer activity of 5-FU for advanced cases was clarified. We conducted a randomized comparative study of surgical adjuvant chemotherapy comparing cis-diamminedichloroplatinum (CDDP), 5-FU and dl-leucovorin (LV) (PFL therapy) with dl-LV and 5-FU (FL therapy) in patients who underwent curative resection of stage II and III colorectal carcinoma. METHODS: Thirty-one patients, 13 ungergoing PFL therapy and 18 undergoing FL therapy, completed the scheduled administration, while 20 dropped out. Administration schedules were as follows: PFL therapy consisted of 13 mg/m2 CDDP, 300 mg/m2 5-FU and 30 mg/body weight LV for 5 consecutive days. The FL therapy consisted of 300 mg/m2 5-FU and 30 mg/body weight LV for 5 consecutive days in hospital. Both regimens were followed by biweekly administration of the same dosages of LV and 5-FU in an outpatient setting. RESULTS: Seven of 23 patients in the PFL therapy group and five of 28 patients in the FL therapy group experienced recurrence of colorectal carcinomas. Regarding prognosis of stage II patients, both groups showed similar results in 5-year disease specific survival and disease-free survival. However, stage III patients obtained better prognostic results in the FL therapy group than in the PFL therapy group. Major toxicities in these regimens were vomiting and leukopenia, both being more frequent in the PFL therapy group. Symptoms of toxicity resolved completely in all patients. CONCLUSION: From the present study we found that PFL therapy brought no benefit for stage II and III colorectal carcinoma compared with FL therapy. We should search for more appropriate adjuvant therapy, increasing the therapeutic effect of 5-FU + LV for stage II and III colorectal carcinoma.     

Systemic gemcitabine combined with intra-arterial low-dose cisplatin and 5-fluorouracil for advanced hepatocellular carcinoma： Seven cases

The combination of intra-arterial low-dose cisplatin and 5-fluorouracil （5-FU） is effective against advanced hepatocellular carcinoma （HCC）. Systemic gemcitabine chemotherapy seems effective in many cancers. We report the results of combination therapy with systemic gemcitabine, intra-arterial low-dose cisplatin and 5-FU （GEMFP）. Seven patients with non-resectable advanced HCC were treated with GEMFP. One course of chemotherapy consisted of daily intra-arterial cisplatin （20 mg/body weight/hour on d 1, 10 mg/body weight per 0.5 h on d 2-5 and 8-12）, followed by 5-FU （250 mg/body weight per 5 h on d 1-5 and 8-12） via an injection port. Gemcitabine at 1000 mg/m2 was administered intravenously at 0.5 h on d 1 and 8. The objective response was 57%. The response to GEMFP was as follows： complete response （no patients）, partial response （four patients）, stable disease （three patients）, and progressive disease （no patients）. The median survival period was 8 mo （range, 5-55）. With regard to the National Cancer Institute Common Toxicity Criteria （NCI-CTC） grade 3 or 4 adverse reactions, seven （100%）, seven, six （86%） and one （14%） patients developed leukopenia, neutropenia, thrombocytopenia and anemia, respectively. GEMFP may potentially be effective for non- resectable advanced HCC, but it has severe hematologic toxicity.     

FOLFOX4方案治疗晚期胃癌的临床观察

目的 观察FOLFOX4方案治疗晚期胃癌的近期疗效和毒副反应.方法 30例晚期胃癌患者,先给予FOLFOX4方案,即:奥沙利铂(L-OHP)85 mg/m2静脉点滴2 h,d1;亚叶酸钙(CF)200 mg/m2静脉点滴2 h,d1、d2,随后5-氟尿嘧啶(5-FU)400 mg/m2静脉推注,d1、d2,5-FU 600 mg/m2微泵持续滴注22 h,d1、d2.2周重复.4个周期后以WHO评价标准评价疗效和毒性.结果 全组30例均可评价,其中完全缓解(CR)2例,部分缓解(PR)16例,稳定(SD)7例,进展(PD)5例,总有效率(CR+PR)60%.中位肿瘤进展时间(TTP)5.5月,中位生存时间(MST)为9个月.毒副反应主要是骨髓抑制,白细胞降低发生率达83.3%,其次为胃肠道反应,恶心呕吐发生率为80.0%,口腔粘膜炎为21.3%,腹泻36.7%,无Ⅳ度胃肠道反应,周围神经毒性发生率为50.0%.结论 FOLFOX4方案治疗晚期胃癌的近期疗效较好,毒副反应可以耐受,值得进一步研究应用.     

Anasarca, a complication of chemotherapy with gemcitabine in two patients with pancreatic cancer

Pancreatic adenocarcinoma is the fifth most common cause of cancer-related mortality in the world. The nucleoside analogue gemcitabine is the established standard therapy for advanced disease. Rare cases of gemcitabine-associated systemic capillary leak syndrome have been reported. Here, we present two cases of capillary-leak syndrome in patients with pancreatic cancer treated with gemcitabine.     

The clinical efficacy of adjuvant systemic chemotherapy with gemcitabine in node-positive pancreatic cancer

BACKGROUND/AIMS: The effects of gemcitabine in postoperative adjuvant chemotherapy were evaluated in patients suffering from locally advanced pancreatic cancer with lymph node metastases. The results were compared with those of our historical control patients treated by surgery alone. METHODOLOGY: Twenty-one patients with node-positive pancreatic cancer who had undergone a pancreatic resection with curative intent over the five years up to February 2003, were enrolled in this study. Nine cases received postoperative adjuvant chemotherapy with biweekly administration of 1000 mg/m2 gemcitabine, while the remaining 12 cases underwent surgery without any adjuvant chemotherapy. RESULTS: The chemotherapy was well tolerated with only mild symptomatic and hematologic toxicities. The overall cumulative survival rates of the chemotherapy and surgery-alone groups were 86% and 75% at one year, and 50% and 0% at two years, with a median survival of 20.3 months and 15.4 months, respectively (p=0.0084). The disease-free interval was also significantly greater in the chemotherapy group compared with the surgery-alone group (p=0.0244). CONCLUSIONS: Adjuvant systemic chemotherapy utilizing gemcitabine was feasible with acceptable adverse effects and improved the survival rate of patients with node-positive pancreatic cancer. Although further investigation is needed to confirm these results, gemcitabine is a promising agent for the treatment of resectable advanced pancreatic cancer.     

Effect of chemotherapy with 5-fluorouracil on intestinal permeability and absorption in patients with advanced colorectal cancer

5-Fluorouracil (5-FU), in association with leucovorin (LV), is the most used chemotherapy agent in the treatment of colorectal cancer. Response rate, as well as side-effect incidence, increases with the dose intensity of regimens that are used. The most common dose-limiting toxicity for 5-FU/LV modulation is diarrhea. To assess the modification of small intestinal function, we investigated the changes in intestinal permeability (IP) and intestinal absorption (IA) in 41 chemo-naive patients (21 men and 22 women; mean age, 61 +/- 9 years) with advanced colorectal cancer after treatment with the association of folinic acid and 5-FU. After chemotherapy administration, we found a marked increase in IP and a reduction in IA, measured as cellobiose-mannitol (CE-MA) ratio (p < 0.0001) and D-xylose absorption (p = 0.0001), respectively. Patients who experienced diarrhea have an increase in CE-MA ratio and a reduction in D-xylose absorption values, both statistically significant. Cellobiose-mannitol ratio and D-xylose absorption tests can be used for the assessment of toxic effect of 5-FU on mature intestinal epithelium and also for evaluating the role of cytoprotective agents.     

Palliative pancreatectomy with postoperative gemcitabine for patients with advanced pancreatic cancer

Background The prognosis of patients with advanced pancreatic cancer remains very poor. This study was designed to evaluate palliative pancreatic resection with postoperative gemcitabine chemotherapy. Methods A total of 127 patients underwent palliative pancreatectomy or palliative nonresectable treatment with gemcitabine at Kobe University Hospital and were analyzed. Results The median survival of patients receiving palliative pancreatectomy with gemcitabine was 15 months, and the 1- and 3-year survival rates were 60% and 13%, respectively, while that of patients receiving gemcitabine alone was only 8 months, and their 1- and 3-year survival rates were 26% and 0%. Multivariate analysis showed that gemcitabine was the strongest factor in survival, and no distant metastasis and pancreatectomy were also significant factors. In addition, the median survival of patients undergoing microscopically incomplete resection with gemcitabine was 22 months, and the 1- and 3-year survival rates were 60% and 40%. Pancreatectomy with gemcitabine improved the performance status 3 months after surgery, with longer survival compared with the gemcitabine alone group. Conclusions Microscopically incomplete pancreatectomy with postoperative gemcitabine chemotherapy has a possible role in advanced pancreatic cancer.     

Phase II study of leucovorin, 5-fluorouracil and gemcitabine for locally advanced and metastatic pancreatic cancer (FOLFUGEM 2)

AIM: FOLFUGEM 1 (leucovorin 400 mg/m2 combined with 5-flurorouracil (FU) bolus 400 mg/m2 then 5-FU 2-3 g/m2/46 hours and gemcitabine 1000 mg/m2 in 30 min) in patients with locally-advanced and metastatic pancreatic adenocarcinoma appeared to be toxic (neutropenia and alopecia). The aims of this phase II multicentric study were to evaluate the response rate, clinical benefit and tolerance of a new scheme of combined leucovorin, 5-FU and gemcitabine (FOLFUGEM 2). PATIENTS AND METHODS: FOLFUGEM 2 associated leucovorin 400 mg/m2 in 2 hours followed by 5-FU 1000 mg/m2 in 22 hours, then gemcitabine 800 mg/m2 (10 mg/m2/min) with cycles every 14 days. Gemcitabine dose could be increased (1000 then 1250 mg/m2) when NCI/CTC toxicity was < or = grade 2. RESULTS: Fifty-eight patients were included (locally-advanced tumor: N = 13 and metastatic: N = 45). Among the 39 patients with measurable disease, 11 had partial response (28.2%, 95% confidence interval: 14-42%) and 11 had stable disease (28.2%). On an intent-to-treat analysis, the objective response rate was 19% (95% confidence interval: 9-29%). Clinical benefit rate was 46%. Median progression-free survival and median overall survival were 3.1 and 7.2 months, respectively. There were 13% grade 3-4 neutropenia and 36% complete alopecia. CONCLUSION: FOLFUGEM 2 schema has an antitumoral effect in advanced pancreatic cancer and has an acceptable toxicity which appears to be less than that of FOLFUGEM 1.