Phase II clinical trial of 5-fluorouracil, trimetrexate, and leucovorin (NFL) in patients with advanced pancreatic cancer

Background. Advanced pancreatic cancer has limited treatment options. 5-fluorouracil (5-FU) is frequently used in the treatment of pancreatic cancer. Preclinical studies suggest synergism between trimetrexate (TMTX), 5-FU, and leucovorin (NFL). Aim. We conducted a phase II trial to evaluate the activity and safety of NFL in pancreatic cancer. Method. Eligible patients (n=21) with untreated advanced pancreatic cancer were treated with 110 mg/m² intravenous (IV) THTX on day 1 and 200 mg/m² IV leucovorin prior to 500 mg/m² IV 5-FU on day 2. Oral leucovorin (15 mg every 6 h for seven doses) started intravenous 24 h later. Results. Treatment was administered for 6 wk followed by a 2-wk rest period. Response was evaluated every 8 wk. All patients were evaluable for response and toxicity. Most patients (80%) had distant metastases. Forty-five cycles of chemotherapy were administered. The most common serious toxicities were Grade 3 diarrhea (23.8%) and nausea and vomiting (14.2%). The response rate was 4.1% (95% CI, 0–23%), median survival was 6.8 mo, and 1-yr survival was 19%. Conclusion. Treatment with NFL is well-tolerated in patients with advanced pancreatic cancer. The median survival and 1-yr survival in these patients with poor prognosis compares favorably with other treatment options.     

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 II trial of 5-fluorouracil,high-dose leucovorin calcium,and dipyridamole in advanced prostate cancer

Summary To examine the effect of altering intracellular folate pools on the efficacy of 5-fluorouracil (FUra) in the treatment of advanced prostate cancer, we performed a phase II trial of FUra (300–370 mg m^–2 day^–1×5 as an i.v. bolus) combined with high-dose folinic acid (500 mg m^–2 day^–1×5.5 days by continuous i.v. infusion) and dipyridamole (75 mg p.o. every 6h×5.5 days) administered on a 28-day schedule in patients with stage D₂ disease. A group of 13 patients have been treated. The median age was 68 years (range 48–78 years); the performance status ranged from 50% to 90%. Among 12 evaluable patients, there were no objective responders; the median time to progression was 1.9 months. Median survival after entry on this trial was 8.6 months. Treatment with FUra, high-dose folinic acid and dipyridamole was well tolerated. Only one episode each of grade 3 leukopenia, granulocytopenia, and thrombocytopenia was observed. These results suggest that, despite previous trials demonstrating activity for FUra in stage D₂ prostate cancer, this disease may be relatively resistant to fluoropyrimidines and, thus, less amenable to biochemical modulation with high-dose folinic acid and dipyridamole.This study was supported, in part, by NCI Cancer Center support grant CA 33572     

Adjuvant chemotherapy in curative resected colon carcinoma: 5-fluorouracil/leucovorin versus high-dose 5-fluorouracil 24-h infusion/leucovorin versus high-dose 5-fluorouracil 24-h infusion

Background Adjuvant postoperative treatment with 5-fluorouracil (5-FU) and leucovorin in curatively resected stage III colon cancer significantly reduces the risk of cancer recurrence and improves survival. The impact of continuous 5-FU with and without leucovorin on survival and tumor recurrence was analyzed in this study compared with the effects of bolus 5-FU/leucovorin.Patients and methods Patients with a curatively resected UICC stage III colon cancer were stratified according to T, N and G category and randomly assigned to receive one of the three adjuvant treatment schemes: 5-FU 450 mg/m² and leucovorin 100 mg/m² × 5 days every 4 weeks; six cycles, arm A; 24-h infusion of high-dose 5-FU/leucovorin 2,600 mg/m² and 500 mg/m², two cycles of six applications, arm B; 24-h infusion of high-dose 5-FU 2,600 mg/m², two cycles of six applications, arm C.Results One hundred and forty-five patients enrolled into this study were eligible. To date, 28 patients have died; 9 on arm A, 11 on arm B, and 8 on arm C (P was nonsignificant). After a median follow-up time of 45 months, there was no statistical difference in survival and tumor recurrence between the three treatment arms. Adjuvant treatment in all arms was generally well tolerated; only a minority of patients experienced grade 3 and 4 toxicities.Conclusion There is no statistical difference in efficacy and toxicity in patients receiving either high-dose 5-FU with or without leucovorin or the standard 5-FU bolus regime after a curative resection of a stage III colon cancer.     

Nab-paclitaxel and gemcitabine for the treatment of patients with metastatic pancreatic cancer

Adenocarcinoma of the pancreas or pancreatic cancer as we will refer to it here, is a cancer of poor prognosis with a high mortality, particularly in the advanced or metastatic setting. Until 2011 and the Phase III results of FOLFIRINOX, standard treatment options were limited to gemcitabine. Combination therapy had shown either a lack of or very limited improvement versus monotherapy with gemcitabine. With the positive results of the MPACT study in 2013 showing improved survival with nab-paclitaxel plus gemcitabine combination therapy, there are now more options for oncologists to treat patients with advanced pancreatic cancer. This paper will highlight the Phase I/II and Phase III trials of nab-paclitaxel plus gemcitabine along with discussing their biology and further possible development in treating patients with pancreatic cancer.     

草酸铂及羟基喜树碱联合亚叶酸钙和氟尿嘧啶治疗进展期结直肠癌的比较

目的：比较草酸铂及羟基喜树碱联合亚叶酸钙、氟尿嘧啶治疗进展期结直肠癌的近期疗效、不良反应和生存期．方法：经病理证实的进展期结直肠癌病例60例,40例(OLF组)采用草酸铂联合亚叶酸钙和氟尿嘧啶方案化疗92个周期,20例(HLF组)采用羟基喜树碱联合亚叶酸钙和氟尿嘧啶方案化疗40个周期,观察化疗不良反应,2-3周期后评价疗效,随访观察无疾病进展生存期、总生存期,统计1a生存率．结果：OLF和HLF组近期有效率分别为30．0%(12/40)和25．0%(5/20),无统计学差异(χ~2 =0．531,P=0．811)；中位无疾病进展生存期分别为6．4和7．3 mo,无统计学差异(u=1．5088,P＞0．05)；中位总生存期分别为10．2和10．8 mo,无统计学差异(u=0．3487,P＞0．05)；1 a生存率分别为34．09%和38．55%,无统计学差异(u= 0．3275,P＞0．05)．两组间Ⅲ,Ⅳ度不良反应均以骨髓抑制和消化道反应为主,其中腹泻发生率HLF组高于OLF组,有统计学差异(χ~2=7．876,P=0．044)．结论：OLF和HLF两方案治疗进展期结直肠癌疗效相似,前者外周神经毒性较常见,后者腹泻更常见．     

Gastric cancer associated with acute disseminated intravascular coagulation: successful initial treatment with weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin

Acute disseminated intravascular coagulation (DIC) is a severe complication of gastric adenocarcinoma, and most of the patients die within 1–3 weeks. We have treated five such patients with an empirical non- myelosuppressive HDFL regimen (weekly 24 h infusion of high-dose 5-fluorouracil 2600 mg/m² and leucovorin 300 mg/m²). Within 2 weeks of starting the treatment the clinical and laboratory evidence of acute DIC quickly resolved in all five patients. HDFL not only caused no further myelosuppression, but also resulted in normalization of the patient's haemogram within a few weeks. Other anti-cancer drugs could then be safely added. Three patients had a survival time of more than 6 months. We suggest that HDFL is an ideal initial treatment for gastric cancer complicated by acute DIC.     

Phase I study of biweekly gemcitabine followed by oxaliplatin and simplified 48-h infusion of fluorouracil/leucovorin for advanced pancreatic cancer

OBJECTIVES: To evaluate the feasibility and maximal tolerated dose (MTD) of oxaliplatin of a triplet regimen consisting of gemcitabine, oxaliplatin and infusional fluorouracil (5-FU)/leucovorin (LV) (GOFL) for advanced pancreatic cancer. PATIENTS AND METHODS: Patients with histologically proven metastatic or unresectable, locally advanced pancreatic adenocarcinoma were eligible to take part in the study. The treatment consisted of fixed-rate infusion (10 mg/m2/minute) of 800 mg/m2 gemcitabine followed by 2-h infusion of oxaliplatin and then 48-h infusion of 5-FU/LV day 1 and day 15 every 4 weeks. The oxaliplatin would be evaluated at three dose levels, 65, 75 and 85 mg/m2. RESULTS: A total of 15 patients were enrolled at three dose levels. Dose-limiting toxicity of neutropenic fever and grade 4 thrombocytopenia occurred in one of each six patients at oxaliplatin dose level of 65 mg/m2 and 85 mg/m2, respectively. The MTD of oxaliplatin for this combination was 85 mg/m2. After a median four cycles of treatment, grade 3/4 neutropenia occurred in 46.7% of patients and thrombocytopenia in 13.3%. Non-hematological toxicities were generally of grade 1/2. Objective tumor response was observed in five patients (33.3%, 95% confidence interval, 6.3-60.4%). CONCLUSION: Biweekly GOFL is a feasible regimen for advanced pancreatic cancer. For further phase II studies, the recommended dose of oxaliplatin is 85 mg/m2.     

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.     

洛铂联合5-氟尿嘧啶与甲酰四氢叶酸治疗晚期胃癌30例

目的:观察洛铂(LBP)联合5-氟尿嘧啶(5-Fu)与甲酰四氢叶酸(CF)治疗晚期胃癌的临床疗效及不良反应.方法:回顾性分析我科2004-03/2008-09收治的30例具有完整临床资料的晚期胃癌患者接受LBP联合5-Fu与CF方案治疗的情况.LBP 30mg/m2静滴,第1天;5-FU 300 mg/m2静滴,第1-5天:CF 100 mg/m2静滴,第1-5天,3 wk为1周期,至少接受2个周期化疗后按照WHO标准评估疗效及不良作用.结果:30例患者共进行124个周期化疗,中位3(2-6)个周期,其中完全缓解(CR)0例,部分缓解(PR)12例,稳定(SD)5例,进展(PD)13例,客观有效率(ORR)为40%(12/30),临床肿瘤控制率(TCR)为56.7%(17/30).不良作用主要是骨髓抑制与胃肠道反应,而肝功能异常及神经系统毒性等较轻,无明显肾毒性和心脏毒性、未发生因化疗产生严重不良作用而终止治疗者和化疗相关性死亡病例.结论:LBP联合5-FU与CF治疗晚期胃癌疗效确切,不良反应可以耐受,值得临床深入研究、推广.     

Randomized trial comparing weekly bolus 5-fluorouracil plus leucovorin versus monthly 5-day 5-fluorouracil plus leucovorin in metastatic colorectal cancer

BACKGROUND/AIMS: The purpose of this study was to compare the efficacy and toxicity profiles of weekly intravenous (i.v.) bolus injection of 5-fluorouracil plus low-dose leucovorin with the Mayo Clinics' monthly 5-day schedule of 5-fluorouracil and leucovorin in the treatment of metastatic colorectal cancer. METHODOLOGY: A total of 96 patients with previously untreated metastatic colorectal cancer were randomized to receive either a weekly i.v. bolus injection of 5-fluorouracil 400 mg/m2 plus leucovorin 20 mg/m2 (weekly arm), or i.v. bolus injection of 5-fluorouracil 425 mg/m2 plus leucovorin 20 mg/m2 for 5 consecutive days every 4 or 5 weeks (monthly arm). Therapy was continued until disease progression or unacceptable toxicity appeared. In the presence of disease progression, the study regimen was stopped and second-line treatment was instituted after the patient was discontinued from this study. RESULTS: There was no significant difference of response rates between both regimens. The response rate were 14.3% in the weekly arm (2 CR and 5 PR, 95% CI: 2.6-25.2%) and 10.6% in the monthly arm (1 CR and 4 PR; 95% CI: 6.5-32.3%), respectively (P = 0.8957). The survival times were also similar between the two (P = 0.4207, log-rank test). The median survival were 15.8 months in the monthly arm and 18.4 months in the weekly arm. Hematologic toxicity was minimal in both arms. However, the monthly arm produced a higher toxicity in severe (grade 3-4) diarrhea (14.9% vs. 2%; P = 0.029) and stomatitis (8.5% vs. 0; P = 0.054). CONCLUSIONS: Weekly bolus injection of 5-fluorouracil and low-dose leucovorin achieved a similar response rate and survival as compared with the Mayo Clinics' monthly 5-day schedule, but severe toxicity was less commonly seen using the weekly regimen. As current chemotherapeutic treatment for metastatic colorectal cancer is largely palliative rather than curative, the weekly bolus regimen may be a more favorable approach in managing metastatic colorectal cancer.     

The effectiveness of nab-paclitaxel plus gemcitabine and gemcitabine monotherapy in first-line metastatic pancreatic cancer treatment: A real-world evidence

Pancreatic cancer is one of the most lethal malignancies with a rise in mortality rates. FOLFIRINOX and nab-paclitaxel plus gemcitabine demonstrated a survival benefit compared to gemcitabine alone. Both protocols are now considered the standard of first-line treatment with no significant difference between them, primarily based on observational studies. Although new therapeutic options have emerged recently, the prognosis remains poor. We conducted a retrospective single-center study on 139 patients treated for metastatic pancreatic adenocarcinoma (mPDAC) with gemcitabine monotherapy (Gem) or nab-paclitaxel + gemcitabine (Nab-P/Gem) in the first line. The aim of our study was to evaluate the effectiveness in terms of overall survival (OS) and progression-free survival (PFS) as well as the influence of patient and disease characteristics on outcomes. Nab-P/Gem resulted in OS of 13.87 months compared to 8.5 months in patients receiving Gem. The same trend was achieved in PFS, 5.37 versus 2.80 months, respectively, but without reaching statistical significance. Furthermore, the 6-month survival in the Nab-P/Gem group was also higher, 78.1% versus 47.8%. In terms of survival, the group of elderly patients, patients of poorer performance, with higher metastatic burden and liver involvement, benefited the most from combination therapy. In our analysis ECOG performance status (p.s.), previous primary tumor surgery, and liver involvement were found to be independent prognostic factors. The addition of nab-paclitaxel to gemcitabine resulted in a significant improvement in the OS of patients with mPDAC. Subgroup analysis demonstrated that patients with some unfavorable prognostic factors benefited the most.     

Bevacizumab plus infusional 5-fluorouracil, leucovorin and irinotecan for advanced colorectal cancer that progressed after oxaliplatin and irinotecan chemotherapy： A pilot study

AIM： To evaluate the combination of bevacizumab with infusional 5-fluorouracil （5-FU）, leucovorin （LV） and irinotecan （FOLFIRI） in patients with advanced colorectal cancer （CRC） pretreated with combination regimens including irinotecan and oxaliplatin. METHODS： Fourteen patients （median age 56 years） with advanced CRC, all having progressed after oxaliplatin- and irinotecan-based combination chemotherapy, were enrolled in this study. Patients were treated with 2 h infusion of irinotecan 150 mg/m2 on d 1, plus bevacizumab 5 mg/kg iv infusion for 90 min on d 2, and iv injection of LV 20 mg/m2 followed by a bolus of 5-FU 400 mg/m2 and then 22 h continuous infusion of 600 mg/m2 given on two consecutive days every 14 d. RESULTS： The median number of cycles of chemotherapy was six （range 3-12）. The response rate was 28.5%, one patient had a complete response, and three patients had a partial response. Eight patients had stable disease. The median time to progression was 3.9 mo （95% CI 2.0-8.7）, and the median overall survival was 10.9 mo （95% CI 9.6-12.1）. Grade 3/4 neutropenia occurred in five patients, and two of these developed neutropenic fever. Grade 3 hematuria and hematochezia occurred in one. Grade 2 proteinuria occurred in two patients. However, hypertension, bowel perforation or thromboembolic events did not occur in a total of 90 cycles. CONCLUSION： Bevacizumab with FOLFIRI is well tolerated and a feasible treatment in patients with heavily treated advanced CRC.     

A phase II study of weekly high-dose 5-fluorouracil and leucovorin plus biweekly alternating doxorubicin and cisplatin for advanced gastric carcinoma

On the basis of recent clinical data suggesting that high-dose continuous 5-fluorouracil (5-FU) is able to overcome resistance to 5-FU bolus application in gastric carcinoma, a phase II study was performed to evaluate the activity and toxicity of weekly high-dose 5-FU and leucovorin plus biweekly alternating doxorubicin and cisplatin as the first-line treatment in patients with advanced gastric carcinoma. Between October 1995 and September 1997, 24 consecutive patients with locally advanced (n = 4) or metastatic (n = 20) gastric carcinomas were treated with a combination of 500 mg/m² leucovorin as a 2-h infusion, followed by 2.0 g/m² 5-FU as a 24-h continuous infusion once weekly for 6 weeks, plus 20 mg/m² doxorubicin as a bolus application and 50 mg/m² cisplatin as a 1-h infusion, week 1, 3 and 5 (FLAP regimen). Response, toxicity and survival data were evaluated. A total of 20 patients were evaluable for response and 24 for toxicity. Objective responses were observed in 11 patients (55%) with no complete remission. Four patients (20%) showed stabilization and 5 patients (25%) experienced progressive disease. The median time to disease progression was 8 months and the overall duration of survival was 14 months. Myelosuppression was significant. In 2 patients, grade 4 WHO thrombocytopenia and leukopenia/anaemia respectively were registered, but there were no treatment-related deaths. We conclude that the weekly alternating FLAP regimen is effective in advanced gastric carcinoma with tolerable toxicity. However, significant myelotoxicity and frequent hospitalization suggest that FLAP should not be preferred to other regimens used in metastatic disease. Currently we intend to establish this regimen in the neoadjuvant setting in patients with primary unresectable localized gastric carcinomas. Received: 15 January 1998 / Accepted: 28 January 1998     

Randomized trial of 5-fluorouracil, leucovorin and cisplatin in advanced pancreatic cancer.

BACKGROUND/AIMS: Phase II trials of combined 5 fluorouracil, leucovorin and cisplatin have demonstrated an 18-28% response rate in advanced pancreatic carcinomas. We investigated the effect of this chemotherapy regime on patients' survival. METHODOLOGY: Patients included gave informed consent. They had an advanced and proven pancreatic adenocarcinoma. The trial was multicentric, prospective and randomized. It compared a 5-day course of leucovorin (200 mg/m2/day), 5-fluorouracil (375 mg/m2/day) and cisplatin (15 mg/m2/day) repeated every 21 days (23 patients) with a control group (22 patients). The main end points were survival time (Kaplan-Meier and log-rank methods) a[not readable: see text]side effects of chemotherapy. RESULTS: Association of leucovorin, 5-fluorouracil and cisplatin failed to demonstrate any advantage of this regimen compared with supported care alone. Median survival times were 8.6 months (SD +/- 1.8) and 7.0 months (SD +/- 0.6), respectively. The modulation of 5-fluorouracil by leucovorin and cisplatin was well tolerated with moderate toxic effects. CONCLUSIONS: This multicentric trial failed to demonstrate any advantage of the evaluated chemotherapy regime in the palliative treatment of cancer of the exocrine pancreas. Other trials including gemcitabine and/or radiotherapy are needed in advanced pancreatic adenocarcinoma.     

Antitumour activity of sunitinib in combination with gemcitabine in experimental pancreatic cancer

BackgroundGemcitabine (Gem) has limited clinical benefits in pancreatic ductal adenocarcinoma (PDAC). Sunitinib (Su) is a novel, multi-target receptor tyrosine kinase inhibitor that has antitumour activities. This study tested the benefits of combined gemcitabine and sunitinib in PDAC.MethodsCell viability and protein expression were evaluated by WST-1 assay and Western blotting. Tumour growth and survival experiments were performed in murine xenografts.ResultsIn PDAC cells, Gem, Su and Su + Gem, respectively, caused 28%, 22% and 48% inhibition in proliferation at 100 nM. In endothelial cells, Gem, Su and Su + Gem, respectively, caused 49%, 32% and 72% inhibition in proliferation. In fibroblasts, Gem, Su and Su + Gem, respectively, caused 65%, 14% and 79% inhibition in proliferation. Su increased apoptosis, as evidenced by the cleavage of caspase-3 and PARP-1 proteins. Net tumour growth compared with controls in the Gem, Su and Su + Gem groups was 57%, 6% and 1%, respectively. Intratumoral proliferative activity was reduced by 33%, 82% and 75% in the Gem, Su and Su + Gem groups, respectively, compared with controls. Median survival in the control, Su, Gem and Su + Gem groups was 16, 21, 24 and 30 days, respectively (P= 0.007).ConclusionsThese findings support a combination approach using multi-target antiangiogenic agents such as sunitinib with standard gemcitabine therapy in the treatment of PDAC.     

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.     

Phase II study of gemcitabine and cisplatin in advanced biliary tract cancer

BACKGROUND: The aim of this phase II study was to determine the efficacy of gemcitabine plus cisplatin chemotherapy in patients with advanced biliary tract cancer. METHODS: Eligibility criteria included histologically confirmed adenocarcinoma with measurable tumor in the biliary tract that was unresectable and either locally advanced or metastatic. Patients received a combination of gemcitabine (1000 mg/m(2) intravenously [IV] on days 1, 8, and 15) and cisplatin (75 mg/m(2) IV on day 1). Cycles were repeated every 28 days. Objective tumor response rates and toxicities were evaluated according to World Health Organization criteria. RESULTS: Twenty-seven patients were enrolled in the study and a total of 120 cycles of chemotherapy were administrated. Objective partial response was observed in nine (33.3%) patients, while stable disease was found in seven (25.9%) patients. The median survival time was 10.0 months and the 1-year survival rate was 36%. Median time to disease progression was 5.6 months. The most common grade 3-4 toxicities were leukopenia (25.9%), anemia (29.6%), thrombocytopenia (22.2%), and vomiting (18.5%). Only one patient was hospitalized for chemotherapy-related complications. CONCLUSION: Gemcitabine and cisplatin combination chemotherapy is an effective, safe, and well-tolerated regimen for the treatment of advanced biliary tract cancer.