5-FU,folinic acid and cisplatin (LV5FU2-P) for unresectable pancreatic cancer

AIM: To prospectively evaluate efficacy and tolerance of the 5-fluorouracil + folinic acid + cisplatin (LV5FU2-P) combination in the treatment of unresectable pancreatic carcinoma. PATIENTS AND METHODS: Between March 1998 and June 2000, 35 patients, mean age 61 years (37-75), with advanced (n=2) or metastatic (n=33) pancreatic cancer and initial performance status (WHO) of 0 (n=9), 1 (n=14) or 2 (n=12) were enrolled in the study. Two consecutive groups of patients were treated twice monthly, the first group (n=19) received the LV5FU2 regimen: a 2 hour-infusion of leucovorin 200 mg/m(2), 5-FU bolus 400 mg/m(2), followed by 22-hour continuous infusion of 5-FU 600 mg/m(2) on 2 consecutive days and cisplatin 50 mg/m(2) on day 2. The second group (n=16) received a simplified schedule with bolus leucovorin 40 mg/m(2), 5-FU bolus 400 mg/m(2) on day 1, followed by 5-FU 2400 mg/m(2) 48-hour infusion and cisplatin 50 mg/m(2) on day 2. Clinical symptoms and performance status were monitored together with weight changes. Tumor assessment was performed every 2 months. RESULTS: Three patients (9%) exhibited grade 4 neutropenia and grade 3 toxicity occurred in 31% of the patients (neutropenia: n=3, thrombocytopenia: n=1, vomiting: n=3, mucositis: n=3, diarrhea: n=1). There were no treatment-related deaths. Objective response was observed in 10 patients (29%, 95% confidence interval: 20-40%) including one complete response. Median progression-free survival and overall survival were 4.5 and 9 months, respectively. Six-months and 1-year survival rates were 70% and 25%, respectively. Weight gain was observed in 40% of the patients and performance status improved in 50%. CONCLUSION: LV5FU2-P regimen is active and well tolerated. It should be compared to gemcitabine as a first line therapy in advanced and metastatic 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.     

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.     

A phase I study of combination of intravenous gemcitabine, oxaliplatin, and 5-FU with daily oral thalidomide (GOFT) in metastatic/locally advanced pancreatic carcinoma patients

BACKGROUND/AIMS: The phase I study was to determine the maximum tolerance dose and dose-limiting toxicity of gemcitabine/oxaliplatin/5-FU/thalidomide (GOFT) in patients with advanced pancreatic cancer. METHODOLOGY: Chemotherapy-naive patients with histologically proven locally advanced or metastatic pancreatic cancer were enrolled. Gemcitabine was given in a 1-hour infusion followed by oxaliplatin in a 2-hour infusion on day 1, and 5-FU in a 24-hour infusion on day 2, and oral thalidomide 100mg was given daily after intravenous chemotherapy. This regimen was given every 2 weeks. Dose levels of regimen were: level I: gemcitabine 1000mg/m2 + oxaliplatin 60mg/ m2 + 5-FU 1000mg/m2 + thalidomide 100mg/day, level II: gemcitabine 1000mg/m2 + oxaliplatin 70mg/m2 + 5-FU 1000mg/m2 + thalidomide 100mg/day, level III: gemcitabine 1250mg/m2 + oxaliplatin 60mg/m2 + 5-FU 1000mg/m2 + thalidomide 100mg/day. The NCI-CTC grade 3/4 toxicity was used for dose-limiting toxicity. Maximum tolerance dose was determined after the first two cycles in each patient. RESULTS: There were 6 patients in level I, 6 patients in level II, and 1 patient in level III. One of the 6 patients had DLT in level I (grade 3 infection and vomiting), 2 of 6 patients had DLT in level II (grade 3 leukopenia) and 1 patient in level III had DLT (grade 3 leukopenia and stomatitis). Other toxicities at level I/II were grade 1/2 leukopenia (7 episodes), grade 1/2 anemia (5), grade 1/2 nausea (5), grade 1 diarrhea (2), grade 1 alopecia (2), grade 1 skin (2), grade 1 allergy (1). CONCLUSIONS: The GOFT regimen was well tolerated and showed good treatment effect on the pancreatic cancer. We recommended the dose of level II GOFT regimen for further phase II trial.     

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.     

FOLFIRI regimen in metastatic pancreatic adenocarcinoma resistant to gemcitabine and platinum-salts

AIM: To evaluate the efficacy and safety of the FOLFIRI regimen in patients with metastatic pancreatic adenocarcinoma (PAC) after the failure of gemcitabine and platinum salts.METHODS: All consecutive patients with histologically confirmed, metastatic PAC and World Health Organization performance status (PS) ≤ 2 received FOLFIRI-1 [irinotecan 180 mg/m² on day 1 and leucovorin 400 mg/m² followed by 5-fluorouracil (5-FU) 400 mg/m² bolus, then 5-FU 2400 mg/m² as a 46-h infusion, biweekly] or FOLFIRI-3 (irinotecan 100 mg/m² on day 1 and leucovorin 400 mg/m², then 5-FU 2400 mg/m² as a 46-h infusion and irinotecan 100 mg/m² repeated on day 3, biweekly) after failure of gemcitabine and platinum-based chemotherapies as a systematic policy in two institutions between January 2005 and May 2010. Tumor response, time to progression (TTP), overall survival rate (OS) and grade 3-4 toxicities were retrospectively studied. Subgroup analyses were performed to search for prognostic factors.RESULTS: Sixty-three patients (52.4% male, median age 59 years) were analyzed. Among them, 42.9% were PS 0, 38.1% were PS 1 and 19.0% were PS 2. Fifty one patients (81.0%) had liver metastases. Before the FOLFIRI regimen, patients had received 1 line (n = 19), 2 lines (n = 39) or 3 lines (n = 5) of chemotherapy. Median TTP obtained with the line before FOLFIRI was 3.9 mo (95% CI: 3.4-5.3 mo). A total of 480 cycles was completed (median: 6 cycles, range: 1-51 cycles). The main reason for discontinuing FOLFIRI was tumor progression (90.3%). Tumor control was achieved in 25 patients (39.7%) (partial response: n = 5, stable disease: n = 20) with FOLFIRI. Median TTP was 3.0 mo (95% CI: 2.1-3.9 mo) and median OS was 6.6 mo (95% CI: 5.3-8.1 mo). Dose adaptation was required in 36 patients (57.1%). Fifteen patients (23.8%) had grade 3-4 toxicities, mainly hematological (n = 11) or digestive (n = 4). Febrile neutropenia occurred in 3 patients. There was no toxic death. PS 2 was significantly associated with poor TTP [hazard ratio (HR): 16.036, P < 0.0001] and OS (HR: 4.003, P = 0.004).CONCLUSION: The FOLFIRI regimen had an acceptable toxicity and an interesting efficacy in our study, limited to patients in good condition (PS 0-1).     

Gemcitabine combined with oxaliplatin is safe and effective in patients with previously untreated advanced pancreatic adenocarcinoma

AIM: The aim of this study was to determine the safety and the efficacy of a gemcitabine/oxaliplatin combination (GEMOX) as first line therapy in patients with metastatic or unresectable locally-advanced pancreatic cancer. PATIENTS AND METHODS: Patients received gemcitabine 1000 mg/m2 as a 10-mg/m2/min infusion on day 1 followed on day 2 by oxaliplatin 100 mg/m2 as a 2-hour infusion, each cycle being given every 2 weeks. All patients had measurable disease and histological diagnosis before inclusion. Patients were treated until progression or for 12 cycles in the absence of progression. Tumor lesions were assessed by computed tomography scan every 4 cycles. RESULTS: Between January 2001 and January 2003, 32 patients were eligible for the study. The objective response rate (OR) was 28.1% with a 12.5% complete response rate (CR). Median progression-free survival and median overall survival were 7 and 9 months, respectively. Median overall survival for patients with metastatic disease and locally-advanced disease were 7 and 25 months, respectively (P < 0.0007). Eleven patients were alive at 1 year (34.4%), six at 2 years (18.8%) and two at 3 years (6%). Fourteen (43.8%) of 32 patients experienced a clinical benefit response. CONCLUSION: These results support the safety, the antitumor activity and the possibility of durable responses of the GEMOX regimen in patients with locally-advanced disease.     

A phase II study of sequential methotrexate and 5-fluorouracil in metastatic pancreatic cancer

BACKGROUND/AIMS: Sequential administration with methotrexate and 5-fluorouracil (sequential MTX/5-FU) has synergistic cytotoxic activity for several malignant diseases, but its activity in pancreatic cancer has not been fully evaluated. The aim of this study was to evaluate the antitumor activity and toxicity of sequential MTX/5-FU in metastatic pancreatic cancer. METHODOLOGY: All patients were required to have a pathologic diagnosis of pancreatic adenocarcinoma with measurable metastatic lesions, and no prior chemotherapy. Sequential MTX/5-FU was administered weekly as followed; MTX 100 mg/m2 intravenous bolus infusion was given, followed 3 h later by 5-fluorouracil 600 mg/m2 intravenous infusion over 30 min. RESULTS: Thirty-one patients were enrolled and assessable for response and toxicity. There were no complete responses, 4 partial responses, 10 no change and 17 progressive disease. The response rate was 12.9% (95% confidence interval: 1.1-24.7%) and the duration of response was 7.1 months (range: 5.5-9.1 months). The median survival was 4.0 months. Chemotherapy was well tolerated, although grade 3-4 toxicities such as neutropenia and diarrhea were seen infrequently. CONCLUSIONS: The sequential MTX/5-FU had marginal antitumor activity with mild toxicity against metastatic pancreatic cancer.     

Intra-arterial continuous infusion for treatment of pancreatic and biliary tract cancer.

BACKGROUND: Systemic chemotherapy does not satisfactorily improve the poor prognosis of pancreas and biliary tract cancer unresectable or metastatic to the liver. Intra-arterial infusion of antineoplastic agents can give higher concentrations to the tumor and slighter concentrations to the whole body, with a potential of efficacy and lower toxicity, due to the hepatic clearance. METHODS: Based on a safe and ambulatorial technique of transcutaneous arterial port implantation, this study was designed to evaluate feasibility and toxicity of 5-fluorouracil (5-FU) intra-arterial continuous infusion combined with systemic gemcitabine with dose escalation. Seventeen patients affected by pancreatic (14) or biliary tract (3) cancer received up to six cycles of treatment. Treatment consisted of intravenous gemcitabine on d 1 and 8 and intra-arterial 5-FU continuous infusion on d 1-14 every 21 d. Dose-escalation levels were 900 and 1000 mg/m2 for gemcitabine and 8, 10, 12, 15, and 17 mg/kg/d for 5-FU. Consecutive cohorts of three patients were planned at each dose level. RESULTS: Gastrointestinal toxicity (vomiting and diarrhea [3rd-4th degree] and gastritis), constituted the dose-limiting toxicity, with a maximum-tolerated dose of 1000 mg/m2 for gemcitabine and 15 mg/kg/d for 5-FU. Hematological toxicity was present in a minority of patients. No patient had acute or later complications such as arterial thrombosis related to the implanted arterial port, sclerosis cholangitis, or chemical cholecistitis. CONCLUSION: 5-Fluorouracil intra-arterial continuous infusion, combined with systemic gemcitabine, seems to be a feasible and safe regimen that could give interesting results in pancreatic cancer.     

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.     

Phase II study of cisplatin combined with weekly gemcitabine in the treatment of patients with metastatic pancreatic carcinoma.

BACKGROUND/AIMS: Combination therapy of gemcitabine and cisplatin has been reported as an effective regimen for advanced pancreatic cancer. However, the toxicity and synergism are known to depend on the schedule of cisplatin. A phase II study was undertaken to determine the efficacy of a single dose of cisplatin in combination with weekly gemcitabine in patients with metastatic pancreatic carcinoma. METHODS: Patients with measurable, metastatic pancreatic carcinoma, not locally advanced diseases, were included. The patients were treated with a combination of gemcitabine 1,000 mg/m(2) i.v. over 30 min administered on days 1, 8, and 15 of each cycle and cisplatin 75 mg/m(2) i.v. administered 6 h after gemcitabine infusion on day 1 with adequate prehydration. Response and toxicity were assessed according to World Health Organization criteria. RESULTS: A total of 52 patients, 5 with recurrent disease after curative operation, were enrolled from January 2000 to March 2004. The objective response rate was 16 of 52 patients (1 complete response and 15 partial response). Disease stabilization was seen in 10 patients (20.8%). The median survival was 11.8 months (95% CI, 10.7-13.0 months), with 76.1% of patients alive at 6 months and 50% alive at 12 months. The median time to progression was 6.1 months (95% CI, 4.16-7.98 months). Major toxicity profiles were thrombocytopenia and neutropenia. CONCLUSIONS: The modified regimen of a single dose of cisplatin per cycle in combination with weekly gemcitabine appeared to have a more favorable therapeutic index and comparable toxicity profiles.     

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.     

Irinotecan plus weekly 5-fluorouracil and leucovorin as salvage treatment for patients with metastatic colorectal cancer: a phase II trial

BACKGROUND: A phase II study was conducted to evaluate the toxicity and efficacy of irinotecan/5-fluorouracil/leucovorin (CPT-11/5-FU/LV (AIO schedule)) as salvage treatment in patients with metastatic colorectal cancer. PATIENTS AND METHODS: 33 patients relapsing after oxaliplatin (L-OHP)-based first-line chemotherapy were enrolled. Their median age was 69 years, 20 (61%) patients were male, and performance status (WHO) was 0, 1, and 2 in 15, 16 and 2 patients respectively; prior surgery 20 (61%) patients; adjuvant chemotherapy 11 (33%) patients, and adjuvant radiotherapy 6 (18%) patients. The number of metastatic sites was 1, 2, and > or =3 in 11, 11, and 11 patients, respectively. CPT-11 was administered on day 1 at the dose of 80 mg/m(2) in 30-90 min infusion and LV (500 mg/m(2)) on the same day as a 2-hour infusion followed by 5-FU (2,600 mg/m(2)/day) as a 22-hour infusion on day 1 for 6 subsequent weeks. The regimen was repeated every 7 weeks. RESULTS: All patients were evaluable for toxicity and for response. Complete response was achieved in 2 patients (6%) and partial response in 4 patients (12%) (RR 18%, CI 5.95-35.43%); 13 patients (40%) had stable disease, and 14 (42%) progressive disease. After a median follow-up period of 9 months, the median duration of response was 5 months, the median time to progression 7.5 months, and OS 14 months. Grade 3-4 neutropenia occurred in 13 patients (39%), febrile neutropenia in 3 (9%), grade 2 anemia in 11 (33%), grade 4 thrombocytopenia in 1 (3%). Grade 3-4 diarrhea occurred in 12 patients (36%), grade 3-4 neurotoxicity in 3 (9%), and grade 3 asthenia in 4 (12%). No treatment-related deaths occurred. The median dose intensity was 85% for CPT-11, and 88% for 5-FU and LV. CONCLUSIONS: The combination of weekly CPT-11 and infusional 5-FU/LV is an active and relatively well-tolerated regimen as salvage treatment in MCC.     

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.     

复方斑蝥胶囊联合化学治疗对转移性结直肠癌的疗效观察

目的 观察复方斑蝥胶囊联合奥沙利铂(L-OHP)、5-氟尿嘧啶/亚叶酸钙(5-FU/CF)组成的FOLFOX4方案治疗转移性结直肠癌的临床疗效及不良反应.方法 收集2006年4月至2008年10月收治的无手术指征的转移性结直肠癌患者107例,随机分为复方斑蝥胶囊联合FOLFOX4方案组(联合治疗组)54例和FOLFOX4方案组53例.联合治疗组给予L-OHP 85mg/m2,第1天静脉滴注2 h,同时或之后予CF 200 mg/m2,静脉滴注2 h,续5-FU 400 mg/m2静脉推注,600 mg/m2持续静脉滴注22 h,次目重复,CF与5-FU每2周重复一次,同时予以复方斑蝥胶囊口服750 mg,每天2次.FOLFOX4方案组患者单纯接受FOLFOX4方案化学治疗.结果 联合治疗组和FOLFOX4方案组有效率分别为44.4%和37.7%,两组间差异无统计学意义(P=0.481).联合治疗组的中位无进展时间(TTP)为11.6个月,FOLFOX4方案组为7.9个月,两组间差异有统计学意义(P=0.020).生活质量评价,联合治疗组的改善率为57.4%,FOLFOX4方案组为32.1%,两组间差异有统计学意义(P=0.008).两组不良反应主要表现为消化道反应、神经系统毒性、脱发和骨髓抑制.联合治疗组Ⅲ/Ⅳ度粒细胞减少发生率为37.0%,FOLFOX4方案组为58.5%,两组间差异有统计学意义(P=0.043).结论 复方斑蝥胶囊联合FOLFOX4方案一线治疗转移性结直肠癌能协同增效,能提高患者TTP及改善患者生活质量,降低粒细胞减少发生.     

Intra-arterial chemotherapy of advanced pancreatic cancer: a single center experience

BACKGROUND/AIMS: The main aim of the present work was to determine response rates and time to progression in patients with locally advanced or metastatic pancreatic cancer treated with intra-arterial chemotherapy. METHODOLOGY: Nineteen chemotherapy-naive patients with measurable lesions were treated with intra-arterial 5-fluorouracil 1000 mg/m2, leucovorin 100 mg/m2, carboplatin 300 mg/m2 and epirubicin 60 mg/m2 (FLEC regimen) every 21 days. Prophylactic granulocyte colony-stimulating factors were administered on days 4-10 of each cycle. RESULTS: There were 16 patients evaluable for response, of whom 4 (25%) had a partial response, 7 (44%) showed stable disease, and 5 (31%) progressed. Marker response rate was 43%. Median time to progression was 4 months and median overall survival was 6 months. One-year overall survival was 16%. No grade 4 toxicity or severe complications relating to the angiographic procedure were observed. CONCLUSIONS: Our results show that intra-arterial FLEC is well tolerated and active against advanced pancreatic cancer.     

Treatment of metastatic colorectal carcinoma with cisplatin and 5-FU

Twenty patients with measurable metastatic colorectal carcinoma were treated every 3 weeks with cisplatin (100 mg/m2 iv) on Day 1 and 5-FU (1000 mg/m2/day by iv infusion over 24 hours) on Days 1-5. Seven patients were previously treated with chemotherapy. The mean performance status for all of the patients was 1.5 (Eastern Cooperative Oncology Group). None of the patients had an objective response to the chemotherapy; 11 patients had stable disease and nine had no response. This study demonstrates that the combination of cisplatin and 5-FU, administered at this dose and schedule, has minimal activity in patients with metastatic colorectal cancer.     

Folfirinox in elderly patients with pancreatic or colorectal cancer-tolerance and efficacy

AIM To study the tolerance and the efficiency of FOLFIRINOX in elderly patients diagnosed with colorectal or pancreatic cancer.METHODS This retrospective study included elderly patients aged over 70 years of age treated at Georges-Francois Leclerc Center by FOLFIRINOX for histological proved colorectal or pancreatic cancer between January 2009 and January 2015. Chemotheapy regimen consisted of oxaliplatin(85 mg/m2 in over 120 min) followed by leucovorin(400 mg/m2 in over 120 min), with the addition, after 30 min of irinotecan(180 mg/m2 in over 90 min) then 5 fluorouracil(5FU)(400 mg/m2 administred intravenous bolus), followed by 5FU(2400 mg/m2 intraveinous infusion over 46 h) repeated every 2 wk. Geriatric parameters were recorded at the beginning. Toxicities were evaluated with the Common Terminology Criteria for Adverse Events 4.03. Tumor response was evaluated by CT scan. Treatment continued until disease progression, unacceptable toxicities or patient refusal.RESULTS Fifty-two patients aged from 70 to 87 years were treated by FOLFIRINOX, 34 had colorectal cancer and 18 had pancreatic cancer. Most of them were in good general condition, 82.7% had a 0-1 performance status and 61.5% had a Charlson Comorbidity Index 10. The most frequent severe toxicities were neutropenia(17 patients, n = 32.7%) and diarrhea(35 patients n = 67.3%); 10 of the case of neutropenia and 5 of diarrhea registered a grade 4 toxicity. Thirty-nine patients(75%) initially received an adapted dose of chemotherapy. The dosage was adjusted for 26% of patients during the course of treatment. Tumor response evaluated by RECIST criteria showed a controlled disease for 25 patients(48.1%), a stable disease for 13 and a partial response for 12 patients. Time under treatment was higher for colorectal cancer with a median time of 2.44 mo(95%CI: 1.61-3.25). Overall survival was 43.88 mo for colorectal cancer and 12.51 mo for pancreatic cancer. In univariate or multivariate analysis, none of geriatric parameters were linked to overall survival. Only the type of tumor(pancreatic/colorectal) was linked in both analysis.CONCLUSION For people over 70 years old, FOLFIRINOX regimen seems to induce manageable toxicities but similar, even higher, median survival rates compared to younger people.     

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.     

Experience with gemcitabine and cisplatin in the therapy of inoperable and metastatic cholangiocarcinoma

AIM: To study the activity of gemcitabine and cisplatin in a cohort of patients with inoperable or metastatic cholangiocarcinoma. METHODS: Chemotherapy-naive patients with pathologically proven cholangiocarcinoma,receiving treatment that consisted of gemcitabine at 1250 mg/m2 in a 30-min infusion on d 1 and 8,and cisplatin at 75 mg/m2 at every 21-d cycle,were retrospectively analyzed. RESULTS: From June 2003 to December 2005,42 patients were evaluated. Twelve patients (28%) had unresectable disease and 30 (72%) had metastatic disease. There were 28 males and 14 females with a median age of 51 years (range 33-67) and median ECOG PS of 1 (range 0-2). A total of 171 cycles were given with a median number of cycles of 4 (range 1-6). There were 0 CR,9 PR,11 SD and 13 PD (response rate 21%). Grade 3-4 hematologic toxicities were: anemia in 33%,neutropenia in 22% and thrombocytopenia in 5%. Non-hematologic toxicity was generally mild. No cases of febrile neutropenia or treatment-related death were noted. The median survival was 10.8 mo (range 8.4-13 mo) and progression free survival was 8.5 mo. One-year survival rate was 40%. CONCLUSION: Our results indicate that the combination of gemcitabine and cisplatin had consistent efficacy in patients with unresectable or metastatic cholangiocarcinoma.