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.     

Beneficial Effects of 5-Fluorouracil and Heparin-Based Portal Infusion Chemotherapy Combined with Mitomycin C and Cisplatin after Curative Resection of Pancreatic Cancer

Aims: We retrospectively assessed the benefits of 5-fluorouracil (5-FU)-and heparin-based portal infusion chemotherapy combined with systemic administration of mitomycin C (MMC) and cisplatin (CDDP) for 4 weeks following surgery (PI4W). The goal was to determine if this treatment prevented liver metastasis and improved survival for patients with potentially curative resection of pancreatic cancer. Methods: 68 patients who underwent pancreatectomy from January 1995 to August 2007 were treated. Of these cases, 22 patients received portal infusion with 5-FU (250 mg/day) for 2 weeks (PI2W) following surgery, while 25 patients received PI4W therapy (250 mg/day of 5-FU with 2,000 IU/day of heparin everyday for 4 weeks, 4 mg MMC on days 6, 13, 20, 27, and 10 mg CDDP on days 7, 14, 21, 28). The remaining 21 patients were treated without adjuvant therapy during the perioperative period. Results: All patients except one completed the portal infusion chemotherapy without toxicity. The cumulative liver metastasis-free survival rate in the PI4W group was significantly higher than those in the other two groups. Furthermore, in the PI4W group, 3-year survival was 91.6% and 5-year survival was 70.5%, rates which were significantly better than those observed in the other two groups. Conclusion: PI4W therapy after surgery is feasible and could become a promising adjuvant therapy in patients with potentially curative resection of 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.     

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.     

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.     

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.     

Phase II study of cisplatin, epirubicin and continuous infusion of 5-fluorouracil in patients with advanced intrahepatic cholangiocellular carcinoma (ICC)

BACKGROUND/AIMS: To clarify the efficacy and toxicity of cisplatin, epirubicin, and continuous infusion of 5-FU (CEF therapy) in patients with advanced intrahepatic cholangiocellular carcinoma (ICC). METHODOLOGY: Chemo-na?ve patients with advanced ICC were treated with cisplatin at 80 mg/m2 and epirubicin at 50 mg/m2 on day 1, and continuous infusion of 5-FU at 500 mg/m2/day on days 1 through 5. If there was no evidence of tumor progression or unacceptable toxicity, the treatment was repeated every 4 weeks, up to a maximum of 6 courses. RESULTS: Thirty-nine patients were enrolled in this study. The median number of courses was 2 (range, 1-6). A partial response was obtained in 4 patients (10%) with a median duration of 2.3 months. Twenty-seven patients (69%) showed no change, and 7 patients (18%) had progressive disease. The median survival time was 9.1 months and the 1-year survival rate was 23%. The progression-free survival time was 5.1 months. Grade 3 to 4 adverse effects were leukocytopenia (51%), neutropenia (74%), thrombocytopenia (23%), and nausea/vomiting (10%). Most of the toxicities were reversible, but 2 patients died of neutropenic sepsis. CONCLUSIONS: CEF therapy has marginal antitumor activity against advanced ICC, although hematological toxicity is the major and most frequent toxicity.     

Radiation therapy combined with cis-diammine-glycolatoplatinum (nedaplatin) and 5-fluorouracil for Japanese stage II–IV esophageal cancer compared with cisplatin plus 5-fluorouracil regimen: a retrospective study

To evaluate the treatment outcome of radiotherapy combined with cis-diammine-glycolatoplatinum (nedaplatin) plus 5-fluorouracil (5-FU) for esophageal cancer. From January 2000 to December 2004, a total of 12 esophageal cancer patients with locally advanced and metastatic esophageal cancer (stages II-IVB) were treated with radiation therapy (50.4 Gy) combined with nedaplatin (80 mg/m(2), bolus infusion) and 5-FU (800 mg/m(2)/24 h, continuous infusion for 4 days) (NDP group). We compared the data with those of patients during the same period receiving a different chemotherapy regimen consisting of cisplatin (75 mg/m(2), bolus infusion) and 5-FU (1000 mg/m(2)/24 h, continuous infusion for 4 days) (n = 29, CDDP group) combined with the same radiation therapy. The median survival period was 11.5 months in the NDP group and 13.1 months in the CDDP group. The overall survival rates at 1-, 2-, and 3-years were 40%, 13%, and 13% in the NDP group and 56%, 42%, and 8% in the CDDP group (P = 0.2472), respectively. Grade III and IV leukocytopenia was observed in six (50%) and none of the patients in the NDP group and 14 (48%) and seven (24%) in the CDDP group, respectively. Grade III thrombocytopenia was observed in three (25%) in the NDP group and four (14%) in the CDDP group. Radiation combined with nedaplatin and 5-FU is a safe and effective method for treating esophageal cancer. We recommend that NDP should be used rather than dose-reduction of CDDP combined with 5-FU in patients with impaired renal function as indicated by low creatinine clearance value (40-60 mL/min).     

Adjuvant chemotherapy with folinic acid and 5-fluorouracil in patients with locally advanced rectal cancer previously treated by preoperative radiochemotherapy and curative tumor resection

BACKGROUND AND AIMS: The role of postoperative adjuvant chemotherapy in patients with rectal cancer pretreated by preoperative radiochemotherapy (RCT) and curative surgery is still poorly investigated. PATIENTS AND METHODS: We pooled data from both arms of a phase III trial in which patients with locally advanced (T3/4) rectal cancer were randomized to preoperative RCT alone or combined with pelvic radio-frequency hyperthermia. After surgery, R0-resected patients were scheduled to adjuvant chemotherapy with four monthly courses of 50 mg folinic acid (FA) and gradually escalated 5-fluorouracil (5-FU, 350-500 mg/m2, days 1-5). Reasons preventing initiation of chemotherapy and treatment-related toxicities were evaluated. Patients' characteristics and survival parameters were compared between the treated and untreated patient groups. RESULTS: Out of 93 patients, 73 (79%) started adjuvant chemotherapy, whereas 19 (21%) did not, mostly due to perioperative complications and refusal. Chemotherapy-related toxicities were mild to moderate in most cases, but--together with protracted postoperative complications--prevented the intended dose escalation of 5-FU in 71% of patients. Distant-failure-free (p=0.03) and overall survival (p=0.03) were improved in the chemotherapy group, although there was a negative selection of patients with unfavourable characteristics into the untreated patient group. INTERPRETATION/CONCLUSION: Adjuvant chemotherapy using FA and 5-FU can be safely applied to the majority of patients with rectal cancer pretreated by RCT and surgery. Survival data are not suitable to allow far-reaching conclusions, but are in line with suggestions of a favourable effect of adjuvant chemotherapy in these patients.     

Folinic acid, 5-fluorouracil and etoposide after curative resection for gastric cancer

BACKGROUND/AIMS: The aim of this study was to evaluate the survival benefit of adjuvant chemotherapy with etoposide, leucovorin and 5-fluorouracil (ELF) in gastric cancer patients undergoing previous surgery with a curative intent. METHODOLOGY: The clinical outcome of 49 patients with resected gastric cancer treated with adjuvant chemotherapy was compared with that of 85 surgically treated historical controls who did not receive any adjuvant treatment. The chemotherapy regimen consisted of six cycles of daily 1-hour intravenous infusions of folinic acid 100 mg/m2 and 5-FU 400 mg/ m2, and a 2-hour infusion of etoposide 100 mg/m2, for three days every 28 days. RESULTS: The 5-year relapse-free survival was 32% in the adjuvant arm and 27% in the control arm (p = 0.6). At the last follow-up, there were 32 deaths in the adjuvant arm and 60 in the control arm. The median duration of survival was respectively 23 and 19 months, and the 5-year survival rates were 34% and 29% (p = 0.4). The chemotherapy was well tolerated. CONCLUSIONS: Our data suggest that ELF adjuvant treatment is a safe and well tolerable combination chemotherapy in patients with resected gastric cancer, but it does not seem to improve prognosis in comparison with historical controls.     

A combination immunochemotherapy of 5-fluorouracil, cisplatin, leucovorin, and OK-432 for advanced and recurrent gastric carcinoma

BACKGROUND/AIMS: Based on theories of biochemical modulation and immunotherapy, a novel regimen consisting of 5-fluorouracil, cisplatin, leucovorin, and OK-432 (FLPO therapy) was devised for the treatment of patients with advanced and recurrent gastric carcinoma. METHODOLOGY: The 14-day combination therapy consisted of continuous infusion of 5-fluorouracil (250 mg/m2/day), a bolus injection of 10 mg cisplatin and 30 mg leucovorin every other day, and a subcutaneous injection or per oral administration of OK-432 (3KE or 5KE) every other day. Thirty patients completed 59 courses of treatment consisting of 2 weeks of therapy followed by at least 2 weeks rest. RESULTS: The overall response rate was 40%, with 1 complete response and 11 partial responses observed. All twelve patients responded after 1 course of treatment. The response rate differed depending upon tumor location, 22.2% at the primary site, 60.0% in the lymph nodes, 45.5% with peritoneal dissemination, 44.4% with liver metastases, 50.0% in the lung, and 100.0% with skin metastases. The most frequently observed toxicity was stomatitis (53.3%). The overall incidence of toxicities of grade 3 or greater was 6.6%, including diarrhea (3.3%) and stomatitis (3.3%). One patient required treatment interruption because of the grade 3 toxicity of diarrhea. The median survival time was 198 days overall, 242 days for responders and 125 days for non-responders. CONCLUSIONS: FLPO therapy seemed to be an effective regimen for the treatment of advanced and recurrent gastric carcinoma.     

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.     

Bolus administration of cladribine in the treatment of Waldenström macroglobulinaemia

This phase II clinical trial evaluated bolus cladribine as a single agent in Waldenström macroglobulinaemia (WM).
Cladribine was administered to 20 patients at a dose of 0.12 mg/kg/d by 2 h intravenous infusion for 5 consecutive days at monthly intervals for three courses. Partially responding patients were continued on therapy until maximal response and/or prohibitive toxicity, to a maximum of eight courses. Complete responders were treated with one additional course of cladribine.
After a median of three courses of cladribine, all 20 patients were evaluable; one achieved a complete response (CR) (5%) and 10 achieved a partial response (PR) (50%). The median duration of response follow-up was 28 months (range 1–37 months). Four of 7 (57%) untreated and 7/13 (54%) previously treated patients responded. The major toxicity encountered was myelosuppression with 60% of patients demonstrating grade 3 or 4 neutropenia. Non-haematological toxicities included two patients with herpes zoster and two patients with non-melanoma skin cancers. At a median follow-up duration of 20 months, 17 patients remain alive and three have died.
We confirm that bolus cladribine is an effective and safe method of drug delivery in WM patients. Recommendations regarding the equivalence of the continuous infusion and bolus methods in untreated patients requires further study. Bolus cladribine is more convenient and less costly than infusional cladribine since it obviates the need for central catheters and infusional devices.     

A combination chemotherapy of 5-fluorouracil and cisplatin against advanced gastric cancer

BACKGROUND/AIMS: This study was designed to clarify the effects of treatment and toxicity between 5-fluorouracil (5-FU) plus bolus infusion of Cisplatin (CDDP) and 5-FU plus continuous infusion of low-dose CDDP in advanced gastric cancer. METHODOLOGY: Seventy-three patients with advanced gastric cancer were enrolled in this study to compare the antitumor effect and toxicity between the bolus infusion of CDDP and the continuous infusion of low-dose CDDP in combination with the continuous infusion of 5-FU. Sixty-five eligible patients were divided into two groups: group A: curative resection cases; and, group B: non-curative, recurrent or inoperable cases. Patients were classified into two arms in each group. One arm of treatment regimen is 5-FU and bolus infusion of CDDP (A-1, B-1) and the other arm is 5-FU and continuous infusion of low-dose CDDP (A-2, B-2). RESULTS: Response rates were 9.1% and 38.5% in arm B-1 and arm B-2, respectively, although the difference between the two was not at a significant level. Frequently observed toxicities during the treatment were gastrointestinal symptoms such as nausea, vomiting, and anorexia. The incidence of side effects in arm A-2 and arm B-2 was almost the same as that in arm A-1 and arm B-1. CONCLUSIONS: These results revealed that there was no advantage of low-dose continuous infusion of CDDP with 5-FU in terms of response rate and clinical toxicity in our present study.     

A phase I dose-escalating study of docetaxel plus folinic acid and 5-fluorouracil in anthracycline-pretreated patients with metastatic breast cancer

BACKGROUND: Since the need for nonanthracycline-containing chemotherapy regimens increases with the increased use of anthracyclines in earlier stages of breast cancer, we investigated the feasibility of the combination of docetaxel and 5-fluorouracil (5-FU) with folinic acid (FA). PATIENTS AND METHODS: Anthracycline-pretreated patients with metastatic breast cancer were eligible. Docetaxel was administered as a one-hour infusion every three weeks on day 1, FA 500 mg/m2 (fixed dose) as a two-hour infusion on days 1 and 15 and 5-FU as a 24-hour infusion on days 1 and 15. The dose levels tested were (docetaxel/5FU in mg/m2): 60/1800, 75/1800, 85/1800, 100/1800, and 100/2100. RESULTS: Altogether 28 patients were accrued and treated in this multicentre open-label study. Dose-limiting toxicities (DLTs) were not observed at dose level I, and in two patients in each of the higher dose levels. DLTs observed were grade III/IV infection (n=4), febrile neutropenia (n=2), diarrhoea (n=1) and erythema (n=1). Partial responses were observed in 10 out of 24 evaluable patients (42%, 95% confidence interval 22.1 to 63.4%). Dose escalation beyond the highest dose level (100/2100) was deemed inappropriate, because these dose levels correspond to recommended dose levels for each drug as a single agent. CONCLUSION: Combination of docetaxel (100 mg/m2, one-hour infusion q3 weeks on day 1), FA (500 mg/m2, two-hour infusion on days 1 and 15) and 5-FU (2100 mg/m2, 24-hour infusion on days 1 and 15) is a feasible regimen with encouraging activity in anthracycline-pretreated patients.     

A observational study of the efficacy and safety of capecitabine versus bolus infusional 5-fluorouracil in pre-operative chemoradiotherapy for locally advanced rectal cancer

Background and objectives

This study is to evaluate the safety and efficacy of preoperative radiotherapy (RT) combined with bolus infusional 5-fluorouracil (5-FU) or oral capecitabine in patients with locally advanced rectal cancer (LARC).

Materials and methods

Seventy-four patients were retrospectively analyzed. Twenty-seven patients were treated with 5-FU (350?mg/m² IV bolus) and leucovorin (20?mg/m² IV bolus) for 5?days/week during week 1 and 5 of RT. Forty-seven patients were treated with capecitabine (850?mg/m², twice daily for 5?days/week). Both groups received the same RT course (45–50.4?Gy/25 fractions, 5?days/week, for 5?weeks). Patients underwent surgery in 6?weeks after completion of the chemoradiotherapy. Data of the observational study were collected.

Results

Grade 3 or 4 toxicities occurred in 40.7% (5-FU) and 19.1% (capecitabine) of the patients (P?=?0.044). Six patients in the 5-FU group (22.2%) and six patients in the capecitabine group (14%) achieved complete response. Primary tumor (T) downstaging were achieved in 51.9% (5-FU) and 69.8% (capecitabine) of the patients. The pathological ypT0-2 stage was 40.7% (5-FU) and 67.4% (capecitabine) (P?=?0.028).

Conclusions

In consideration of the better ypT0-2 downstaging rate, less severe toxicities, and no need for indwelling intravenous device on oral capecitabine regimen, the administration of oral capecitabine with RT may be a more favorable option in the neoadjuvant treatment for LARC.     

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.     

Combination chemotherapy comprising 5-fluorouracil,leucovorin, etoposide,and cis-diamminedichloroplatinum for the treatment of advanced gastric cancer

PURPOSE: The FLEP regimen (5-FU, LV, ETP, and CDDP) has been recommended as a combination chemotherapy to control advanced and recurrent gastric cancer. We performed a phase II study of this regimen in 49 patients with advanced gastric cancer. METHODS: The treatment regimen consisted of: 5-FU at 370 mg/m(2) (days 1-5, i.v. 24 h); LV at a dose of 30 mg (days 1-5, i.v. bolus); and ETP and CDDP each at 70 mg/m(2) (days 7 and 21, i.a. 2 h), which was repeated every five weeks. RESULTS: The overall response rate was 40.8% (20/49 patients) and the median survival time was 12.6 months (range 1.1-41.8). The adverse events were Grade 3/4 leukocytopenia (16.3%), Grade 3/4 thrombocytopenia (8.2%), Grade 3 nausea and/or vomiting (4.1%), and Grade 3 stomatitis (2.0%). CONCLUSIONS: Based on the encouraging response rate and prognosis, we recommend applying the FLEP regimen to patients with primary advanced gastric cancer.     

Phase I trial of combination therapy with PALA and 5-FU

PALA is an inhibitor of de novo pyrimidine biosynthesis. Studies combining PALA with 5-FU in experimental models have demonstrated synergistic antitumor activity with only additive toxicity. The phase I study of PALA in combination with 5-FU is described. Sixteen patients received a total of 29 courses of PALA given as a 24-hour infusion daily for 5 days and 5-FU given by iv bolus at the end of each 24-hour PALA infusion. Cycles were repeated at 28-day intervals. Mucositis was dose-limiting when 940 mg/m3/day of PALA was given with 345 mg/m2/day of 5-FU. Diarrhea, skin rash, and myelosuppression (in decreasing order of frequency) occurred but were not dose-limiting. Alopecia occurred in all patients. Objective responses were seen in single patients with large cell carcinoma of the lung, fibrous histiocytoma, and adenocarcinoma of the colon refractory to prior 5-FU therapy. These studies support further phase II evaluation of the PALA and 5-FU combination.     

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.