Weekly high-dose 5-fluorouracil and folinic acid as salvage treatment in advanced gastric cancer

BACKGROUND: A weekly schedule of a 24-h high-dose 5-FU infusion in combinationwith folinic acid was investigated as salvage therapy in patientswith advanced gastric cancer. PATIENTS AND METHODS: Seventeen patients with progressive disease after chemotherapywere treated with a weekly schedule of 500 mg folinic acid/sqmby i.v. 2-h infusion followed by an i.v. 24-h infusion of 2.6g 5-FU/sqm times six. Fourteen of the 17 patients (82%) hadbeen pretreated in regimens which included 5-FU/folinic acidi.v. bolus. RESULTS: Toxicity was mild, with diarrhea, mucositis and nausea; WHOgrade m/IV diarrhea was observed in only two patients. Threepatients achieved partial remissions (18%; 95% confidence interval:0%–38%) and 7 patients stable disease (41%; 95% confidenceinterval: 17%–64%). Their median survival time was fivemonths (range 1.5–10 months) after the onset of salvagetherapy. CONCLUSIONS: This schedule of weekly 24-h infusions of high-dose 5-FU andfolinic acid is effective, even in patients pretreated withor resistant to regimens including 5-FU/folinic acid i.v. bolus.Based on these data, it appears that this schedule of high-dose5-FU/folinic acid in first-line combination chemotherapy meritsinvestigation. 5-fluorouracil, folinic acid, gastric cancer, salvage therapy     

Phase II study of weekly oxaliplatin and 24-h infusion of high-dose 5-fluorouracil and folinic acid in the treatment of advanced gastric cancer

To investigate the efficacy and safety of combining weekly oxaliplatin with weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and folinic acid (FA) in treatment of patients with advanced gastric cancer. Patients with histologically confirmed, locally advanced or recurrent/metastatic gastric cancer were studied. Oxaliplatin 65 mg m(-2) 2-h intravenous infusion, and 5-FU 2600 mg m(-2) plus FA 300 mg m(-2) 24-h intravenous infusion, were given on days 1 and 8, repeated every 3 weeks. Between January 2001 through January 2002, 55 patients were enrolled. The median age was 64 years (range: 22-75). In all, 52 patients (94.5%) had recurrent or metastatic disease and three patients had locally advanced disease. Among 50 patients evaluable for tumour response, 28 patients achieved partial response, with an overall response rate of 56% (95% confidence interval (CI): 41.8-70.3%). All 55 patients were evaluated for survival and toxicities. Median time to progression and overall survival were 5.2 and 10.0 months, respectively, during median follow-up time of 24.0 months. Major grades 3-4 toxicities were neutropenia in 23 cycles (7.1%) and thrombocytopenia in 16 cycles (5.0%). Treatment was discontinued for treatment-related toxicities in nine patients (16.4%), of whom eight were due to oxaliplatin-related neurotoxicity. One patient (1.8%) died of neutropenic sepsis. This oxaliplatin-containing regimen is effective in the treatment of advanced gastric cancer. Except for neurotoxicity that often develops after prolonged use of oxaliplatin, the regimen is well tolerated.     

周剂量多西紫杉醇联合顺铂和5-氟尿嘧啶治疗晚期胃癌

  目的 观察周剂量多西紫杉醇联合顺铂（DDP）、5-氟尿嘧啶（5-Fu）治疗晚期胃癌的临床疗效和毒副作用。方法 晚期胃癌患者28例，给予多西紫杉醇35 mg／m2，静脉滴注1 h，第1、8、15天；DDP 75 mg／m2，均分第1 ~ 3天静脉滴注，5-Fu 500 mg／m2，24 h中心静脉置泵持续滴注，第1 ~ 5天，28 d为1个周期。化疗2 ~ 6个周期后按WHO实体瘤疗效评价标准（RECIST）评定疗效，按WHO标准评价不良反应。结果 全组28例均可评价疗效，其中完全缓解（CR）2例，部分缓解（PR）13例，稳定（SD）7例，近期客观有效率53.4 %，中位疾病进展时间（TTP）为8.7个月，中位生存期（MS）为11.8个月，1年生存率为47.8 %。主要不良反应为骨髓抑制和胃肠道反应。但Ⅲ ~ Ⅳ度发生率较低。结论 周剂量多西紫杉醇联合DDP和5-Fu治疗晚期胃癌疗效较好，患者毒副作用轻，耐受性好，值得进一步推广使用。     

Phase II study of oxaliplatin, 5-fluorouracil and leucovorin in previously platinum-treated patients with advanced gastric cancer.

BACKGROUND: Oxaliplatin shows preclinical activity in many cancer cell lines that are resistant to cisplatin, and also has synergism with 5-fluorouracil (5-FU). We undertook this study to evaluate the efficacy and toxicities of a combined oxaliplatin, 5-FU and leucovorin (LV) continuous infusion regimen in patients with advanced gastric cancer who progressed during or after treatment with 5-FU and platinum compounds. PATIENTS AND METHODS: Twenty-six patients with advanced gastric cancer, whose disease progressed while receiving, or after discontinuing, chemotherapy with a 5-FU and platinum regimen, were enrolled in this study. Treatment comprised oxaliplatin (85 mg/m2 on day 1) as a 2-h infusion followed by bolus 5-FU (400 mg/m2 on day 1), and 48-h infusion of 5-FU 2.4-3.0 g/m2 concurrently with LV 150 mg/m2. Cycles were repeated at 2-week intervals. RESULTS: Of the 23 evaluable patients, there were six partial responses (response rate 26%). All responding patients were among those who entered into this trial immediately after failure of previous chemotherapy with 5-FU and cisplatin. The median time to progression was 4.3 months and the median overall survival was 7.3 months. The most common hematologic toxicity was grade 1-2 anemia in 39 cycles (39%). No grade 4 leukopenia or thrombocytopenia were observed. The most common non-hematologic toxicity was nausea/vomiting (33%). Peripheral neuropathy of grade 1 or 2 was noted (27%), but there was no grade 3 or 4 neurotoxicity. CONCLUSIONS: This phase II study of oxaliplatin, 5-FU and LV continuous infusion showed activity in previously platinum-treated patients with advanced gastric cancer, with acceptable toxicities.     

Phase I dose-escalating study of 24-h continuous infusion of 5-fluorouracil in combination with weekly docetaxel and cisplatin in patients with advanced gastric cancer

Purpose

To determine the maximum-tolerated dose (MTD) of a 24-h continuous infusion of 5-fluorouracil (5-FU) when administered in combination with a fixed weekly dose of docetaxel and cisplatin in patients with advanced gastric cancer.

Methods

Patients with advanced gastric adenocarcinoma (n = 21) received a weekly regimen of docetaxel, cisplatin and 5-FU (DCF) for 3 consecutive weeks every 4 weeks. The doses of docetaxel and cisplatin were fixed at 33.3 and 30 mg/m², respectively. The dose of 5-FU was increased from a starting dose of 1,000 mg/m² to the MTD.

Results

A total of 53 cycles of chemotherapy were administered (median = 3 cycles/patient). The MTD of 5-FU was 1,750 mg/m². All 21 patients were assessed for toxicity and 19 patients (90%) were evaluated for response. Both grade 3–4 hematologic and non-hematologic toxicities occurred in less than 10% of patients and there were no treatment-related deaths. Among the 19 patients, we observed 1 complete and 4 partial responses for an overall response rate of 26% (95% CI: 6–46%). This rate increased to 39% (95% CI: 12–66%) in 13 chemotherapy-naïve patients.

Conclusions

A consecutive weekly DCF regimen at 4-week intervals appears feasible for advanced gastric cancer with a favorable toxicity profile. The recommended doses are 33.3 mg/m² of docetaxel, 30 mg/m² of cisplatin and 1,500 mg/m² of a 24-h continuous intravenous infusion of 5-FU. The response of this weekly regimen in our study was favorable and deserved further investigation in a phase II trial.     

Whole-body hyperthermia (41.8 degrees C) combined with bimonthly oxaliplatin, high-dose leucovorin and 5-fluorouracil 48-hour continuous infusion in pretreated metastatic colorectal cancer: a phase II study.

BACKGROUND: Second- and third-line treatments remain a challenge in advanced colorectal cancer. Studies of bimonthly regimens of high-dose leucovorin (LV) and 5-fluorouracil (5-FU) by continuous infusion combined with oxaliplatin (L-OHP) have shown encouraging response rates in patients not responding to a bimonthly LV/5-FU regimen. Hyperthermic enhancement of L-OHP efficiency by increased DNA adduct formation has been demonstrated in vitro. This study was designed to address feasibility, toxicity and efficacy issues of whole-body hyperthermia (WBH) as an adjunct to L-OHP/LV/5-FU in pretreated patients after progression to first- and second-line treatments with LV/5-FU by continuous infusion and irinotecan. PATIENTS AND METHODS: Forty-four patients with advanced colorectal cancer, who had progressed during or within 3 months after completion of chemotherapy with LV/5-FU 24-h infusion (LV/5-FU(24h)) (eight patients) or irinotecan combined with or after LV/5-FU(24h )(36 patients), were treated with L-OHP 85 mg/m(2), 2-h intravenous (i.v.) infusion, followed by LV 200 mg/m(2), 1-h i.v. infusion, and 5-FU 3 g/m(2), 48-h continuous infusion. Every second cycle of the biweekly regimen was combined with WBH, thus allowing a comparison of toxicity with and without WBH in the same patient. Whole-body hyperthermia was administered by a humidified radiant heat device. The target temperature of 41.8 degrees C was maintained for 60 min. L-OHP (2-h infusion) was started at a core body temperature of 39 degrees C. RESULTS: All patients could be evaluated for toxicity, and 41 patients were evaluable for response. A total of 273 L-OHP-containing regimens were administered, 130 with and 143 without WBH. Hyperthermic treatment combined with L-OHP/LV/5-FU showed no unexpected toxicities. WHO grade 3 toxicities were rare and evenly balanced between cycles given with or without WBH. One early death occurred due to sepsis and tumor lysis. The overall response rate was 20%, with two complete and six partial responses. Twenty-three patients (56%) had stable disease and nine patients (22%) progressive disease. With a median observation time of 70 weeks, the median time to progression was 21 weeks [95% confidence interval (CI) 17-25 weeks] and the median survival was 50 weeks (95% CI 39-61 weeks) from the start of therapy. CONCLUSIONS: This trial suggests some advantage of combining L-OHP/LV/5-FU with WBH. Results compare favorably with the activity of similar regimens without WBH in less extensively pretreated patients. These data support further evaluation and warrant phase III studies.     

顺铂和 5-氟尿嘧啶 /醛氢叶酸双周疗法治疗鼻咽癌初步报道

目的：观察顺铂（cisplatin,DDP),5－氟尿嘧啶（5-fluorouracil,5-FU)／醛氢叶酸（leucovorin,LV)双周疗法治疗鼻咽癌的疗效及其毒性。方法：病理明确的20例鼻咽癌患者进入研究组。包括：1）初诊时即有远处转移的病人;2）放疗后发生远处转移的病人;（3）初诊时局部晚期的病人;4）放疗后局部复发的病人。治疗方案：LV200mg/m^2,静脉输注2h,后接5－FU375mg/m^2静脉推注10min,再接5－FU3．0g/m^2,用输液泵连续静脉输注48h,以上治疗每两周一次。DDP80mg/m^2,用时水化、28天1次。所有病人至少接受2疗程的治疗。结果：经过两个周期的化疗,完全缓解（complete remission,CR)2例（10％）,部分缓解（prital remission,PR)12例（60％）,6例病人稳定（30％）,,治疗中无疾病进展,无治疗相关的死亡。恶心、呕吐、静脉炎为主要的不良反应,毒性相对较弱。结论：当前研究的数据表明,大剂量DDP合并5－FU／LV双周疗法治疗复发转移或局部晚期的鼻咽癌病人,缓解率较高,毒性相对较低。     

Oxaliplatin with high-dose leucovorin and infusional 5-fluorouracil in irinotecan-pretreated patients with advanced colorectal cancer (ACC)

The purpose of this study was to evaluate the efficacy and tolerance of the bimonthly administration of oxaliplatin in combination with high-dose leucovorin and infusional 5-fluorouracil (5-FU) (FOLFOX2 regimen) in patients with advanced colorectal cancer (ACC) who did not respond or whose disease progressed within 3 months after front-line treatment with CPT-11-containing regimens. Forty-one patients with ACC who did not respond or whose disease progressed after front-line treatment with CPT-11 + 5-FU/leucovorin were enrolled. Oxaliplatin was administered at the dose of 100 mg/m2 on day 1 as a 2-hour infusion simultaneously but through different lines with leucovorin (500 mg/m2 on days 1 and 2); 5-FU was given at the dose of 1,750 mg/m2/d as a 22-hour continuous intravenous infusion on days 1 and 2. The regimen was repeated every 2 weeks. In an intention-to-treat analysis, complete response was achieved in one (2.4%) and partial response in six (14.6%) patients (overall response rate: 17%; 95% CI: 5.56-28.59%); stable disease and progressive disease were observed in 15 (36.6%) and in 19 (46.31%) patients, respectively. The median duration of response and the median time to tumor progression were 6 and 8.5 months, respectively. The median overall survival was 12 months and the probability for 1-year survival was 42.9%. Grade III/IV neutropenia occurred in 17 (41%) patients and febrile neutropenia developed in one of them (2%). There was no treatment-related death. Peripheral neuropathy greater than or equal to grade II occurred in 24 (58%) patients. Other toxicities were relatively mild. The bimonthly administration of oxaliplatin in combination with high-dose leucovorin and 48-hour continuous infusion of 5-FU is a relatively active and well-tolerated regimen for patients with ACC resistant or refractory to CPT-11 + 5-FU (continuous infusion)/leucovorin.     

Infusional 5-fluorouracil, cisplatin and mitomycin C in advanced gastric cancer: a low cost effective regimen

Recently, we reported a highly active regimen in advanced gastric cancer including a weekly administration of cisplatin, epidoxorubicin, leucovorin, 5-fluorouracil with the support of filgrastim. In order to simplify the administration and to decrease the toxicity of these drugs, mainly epidoxorubicin-induced alopecia, we designed a regimen including an infusional 5-fluorouracil schedule according to the de Gramont regimen, cisplatin and mitomycin C replacing epidoxorubicin. Forty-five patients with advanced or metastatic gastric cancer were treated with cisplatin 50 mg m(-2) i.v. on day 1, every 2 weeks, 6S-stereoisomer-leucovorin 100 mg m(-2) i.v. followed by 5-fluorouracil 400 mg m(-2) i.v. bolus and 600 mg m(-2) i.v. in a 22-h infusion, on days 1 and 2, every 2 weeks, and mitomycin C 7 mg m(-2) i.v. bolus on day 2, every 6 weeks. Grades 3-4 toxicities (National Cancer Institute-Common Toxicity Criteria) consisted mainly of neutropenia and thrombocytopenia. Five patients had a complete response and 16 had a partial response for an overall response rate of 46.7% (95% confidence interval, 32.1-61.2%). The median survival was 11 months. The combination of cisplatin, 5-fluorouracil and leucovorin according to de Gramont, and mitomycin C seems to be an active and safe regimen in the treatment of advanced gastric cancer. Because of its low cost it may be suggested for patients not enrolled into clinical trials.     

Combination therapy with cisplatin, 5'-deoxy-5-fluorouridine (5'-DFUR) and mitomycin (MMC) in patients with inoperable, advanced gastric cancer

The optimal dose of cisplatin (CDDP) for combination chemotherapy for the treatment of inoperable, advanced gastric cancer has yet to be established. We therefore performed a randomized study to compare the therapeutic usefulness of two dose levels of cisplatin. 5'-deoxy-5-fluorouridine (5'-DFUR 1,400 mg/m(2)/d) was given orally on days 1 to 4 and 15 to 18. Mitomycin C (MMC, 5.75 mg/m(2)/d) was injected intravenously on day 5. In addition, 80 mg/m2/d of CDDP (regimen A) or 60 mg/m(2)/d of CDDP (regimen B) was given by 2-h intravenous drip infusion on day 5. This treatment cycle was repeated every four weeks. Fifty-six patients were enrolled. Clinical response was evaluated in 32 patients (regimen A, 16 patients; regimen B? 16 patients) with measurable lesions. The response rate was significantly higher with regimen A (9 PR/16, 56.3%) than with regimen B (3 PR/16, 18.9%) (p=0.028, chi(2) test). Median survival was slightly but not significantly longer with regimen A (7.4 months) than with regimen B (6.3 months). Drug toxicity included myelosuppression and gastrointestinal symptoms, but there were no serious adverse reactions or differences in safety between the treatment regimens. Regimen A was associated with a high response rate and low toxicity. The optimal dose of CDDP in combination with 5'-DFUR and MMC for the treatment of advanced gastric cancer is regarded to be 80 mg/m(2).     

Intensified bimonthly cisplatin with bolus 5-fluorouracil, continuous 5-fluorouracil and high-dose leucovorin (LV5FU2) in Patients with advanced gastrointestinal carcinomas: a phase I dose-finding and pharmacokinetic study

5-fluorouracil (5FU) and cisplatin are commonly used in the treatment of gastric cancer. Continuous 5FU appears to be more effective and less toxic than bolus administration, while increasing the dose intensity of cisplatin may be advantageous. We conducted a phase I study to establish the maximum tolerated dose (MTD) of cisplatin, which could be combined with a hybrid bolus/continuous 5-FU regimen (LV5FU2), given every 2 weeks. Thirty-six patients with advanced upper gastrointestinal carcinomas entered the study. Starting cisplatin dose was 40 mg/m2 and it was increased by 10 mg/m2 in cohorts of 3-6 patients. The pharmacokinetics of 5-fluorouracil in 14 patients were compared with those of 6 patients receiving LV5FU2 alone. All patients received prophylactic granulocyte colony-stimulating factor at cisplatin doses > or =50 mg/m2. MTD was reached at 100 mg/m2 of cisplatin and, therefore, the 90 mg/m2 dose is recommended for phase II studies. Bone marrow toxicity was the most frequent dose-limiting toxicity with 1 patient dying of neutropenic sepsis. Grade III/IV neutropenia was observed in 10 patients (27.7%). Nonhematological toxicity was infrequent and mild. Pharmacokinetic analysis showed that the addition of 90 mg/m2 or 100 mg/m2 of cisplatin to LV5FU2 significantly reduced the 5FU area under the curve. Objective response rate in 23 evaluable patients was 39.2%. The combination of LV5FU2 with bimonthly 90 mg/m2 cisplatin is feasible and active and should be further evaluated in patients with advanced gastric cancer.     

CPT-11 (irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer. GERCOR

CPT-11 (irinotecan) has shown activity in patients with advanced colorectal cancer resistant to leucovorin (LV) and 5-fluorouracil (5-FU). In this study, the simplified bimonthly LV-5-FU regimen was combined with CPT-11 (FOLFIRI) as third-line therapy for patients with advanced colorectal cancer. Continuous infusion of 5-FU was administered with disposable pumps as outpatient therapy. FOLFIRI consisted of CPT-11 180 mg/m2 as a 90-min infusion day 1; LV 400 mg/m2 as a 2-h infusion during CPT-11, immediately followed by 5-FU bolus 400 mg/m2 and 46-h continuous infusion of 2.4-3 g/m2 every 2 weeks. Among the 33 patients treated, 2 had partial responses for an overall response rate of 6%; 20 patients were stabilised (61%) and 11 had disease progression (33%). From the start of FOLFIRI, median progression-free survival was 18 weeks and median survival was 43 weeks. For the 242 cycles analysed, NCI-CTC toxicities grade 3-4 per patient were nausea 15%, diarrhoea 12% and neutropenia 15%. Overall, 10 patients (30%) experienced grade 3-4 toxicity. 7 patients (21%) had grade 2 alopecia. FOLFIRI generated activity and acceptable toxicity, in heavily pretreated patients, with limited diarrhoea, mostly asymptomatic neutropenia and manageable nausea and relatively uncommon alopecia. This regimen is suitable for studies in chemotherapy-na?ve patients.     

Optimisation of 5-fluorouracil (5-FU)/cisplatin combination chemotherapy with a new schedule of hydroxyurea, leucovorin, 5-FU and cisplatin (HLFP regimen) for metastatic oesophageal cancer

To improve the efficacy and tolerance of the 5-fluorouracil (5-FU)/cisplatin combination in metastatic esophageal cancer, we designed a new therapeutic schedule, the HLFP regimen. 42 patients with metastatic oesophageal adenocarcinoma (n=10) or squamous cell carcinoma (n=32) were prospectively enrolled in the study. All had bidimensionally measurable disease. The HLFP regimen consisted of twice-monthly oral administration of hydroxyurea 1 g/m(2) on days 0, 1 and 2; a 2-h infusion of leucovorin 200 mg/m(2) and a bolus of 5-FU 400 mg/m(2) followed by a 22-h infusion of 5-FU 600 mg/m(2) on days 1 and 2; and, every two cycles, 80 mg/m(2) cisplatin on day 3. Relief of dysphagia and other symptoms were monitored, together with body weight changes. Major objective responses were observed in 24 patients (57%, 95% Confidence Interval (CI): 42-72%), including four complete responses (10%). The median progression-free survival and overall survival times were 8 and 12.7 months, respectively. Weight gain was observed in 48% of patients, and dysphagia improved in 76%. Grade 3-4 toxicity occurred in 40% of patients, with grade 4 neutropenia in 12% and grade 3 thrombocytopenia, vomiting and diarrhoea in 7-9% of patients. There were no treatment-related deaths. These results suggest that the HLFP regimen is an active and well-tolerated chemotherapy for metastatic oesophageal carcinoma.     

Phase II study of weekly vinorelbine and 24-h infusion of high-dose 5-fluorouracil plus leucovorin as first-line treatment of advanced breast cancer

We prospectively investigated the efficacy and safety of combining weekly vinorelbine (VNB) with weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and leucovorin (LV) in the treatment of patients with advanced breast cancer (ABC). Vinorelbine 25 mg m(-2) 30-min intravenous infusion, and high-dose 5-FU 2600 mg m(-2) plus LV 300 mg m(-2) 24-h intravenous infusion (HDFL regimen) were given on days 1 and 8 every 3 weeks. Between June 1999 and April 2003, 40 patients with histologically confirmed recurrent or metastatic breast cancer were enrolled with a median age of 49 years (range: 36-68). A total of 25 patients had recurrent ABC, and 15 patients had primary metastatic diseases. The overall response rate for the intent-to-treat group was 70.0% (95% CI: 54-84%) with eight complete responses and 20 partial responses. All 40 patients were evaluated for survival and toxicities. Among a total of 316 cycles of VNB-HDFL given (average: 7.9: range: 4-14 cycles per patient), the main toxicity was Gr3/4 leucopenia and Gr3/4 neutropenia in 57 (18.0%) and 120 (38.0%) cycles, respectively. Gr1/2 infection and Gr1/2 stomatitis were noted in five (1.6%) and 59 (18.7%) cycles, respectively. None of the patients developed Gr3/4 stomatitis or Gr3/4 infection. Gr2/3 and Gr1 hand-foot syndrome was noted in two (5.0%) and 23 (57.5%) patients, respectively. Gr1 sensory neuropathy developed in three patients. The median time to progression was 8.0 months (range: 3-25.5 months), and the median overall survival was 25.0 months with a follow-up of 5.5 to 45+ months. This VNB-HDFL regimen is a highly active yet well-tolerated first-line treatment for ABC.     

Optimization of 5-fluorouracil (5-FU)/cisplatin combination chemotherapy with a new schedule of leucovorin, 5-FU and cisplatin (LV5FU2-P regimen) in patients with biliary tract carcinoma.

BACKGROUND: Unresectable biliary tract carcinoma (BTC) is associated with a very poor prognosis. To improve efficacy and tolerance of the 5-fluorouracil (5-FU)/cisplatin combination in BTC, we designed a new therapeutic schedule, the LV5FU2-P regimen. PATIENTS AND METHODS: Twenty-nine patients with advanced or metastatic BTC were prospectively enrolled in the study. The treatment (LV5FU2-P regimen) consisted of a biweekly administration of a 2-h infusion of leucovorin 200 mg/m(2), a 400 mg/m(2) bolus of 5-FU followed by a 22-h continuous infusion of 600 mg/m(2) 5-FU on two consecutive days and cisplatin 50 mg/m(2) on day 2. Clinical symptoms, performance and weight changes were monitored. RESULTS: Objective responses were observed in 10 patients (34%) (95% confidence interval 23% to 45%) including one complete response and nine partial responses (stabilization 38%, progression 28%). Median progression-free survival and overall survival were 6.5 and 9.5 months, respectively. Weight gain was observed in 45% of patients and performance status improved in 60%. One patient had a grade 4 thrombocytopenia, and grade 3 toxicity occurred in 41% of patients. There were no treatment-related deaths. CONCLUSIONS: This study, one of the largest phase II trials performed for this disease, shows that the LV5FU2-P regimen is an active and well-tolerated chemotherapy for advanced and metastatic BTC.     

Weekly administration regimen of paclitaxel (PTX) in patient with inoperable or recurrent gastric cancer

Paclitaxel is one of the new drugs against advanced/recurrent gastric cancer. We report its efficacy and toxicity with weekly administration for advanced/recurrent gastric cancer. We administered 26 patients (postoperative/non-operation=9/17) PTX 80 mg/m(2)by 1-hour intravenous infusion once a week for 3 weeks followed by one week rest. Median PTX administrations were 2.0 cycles (range:1-22). Characteristics of the patients were median age of 62 (range: 37-78) and PS 0/1/2:2/17/7, male/female:18/8. Over grade 3 toxicities did not occur. The overall response rate was 14.3%, and the non-PD rate was 66.8%. Median time to treatment failure was 61 days and median survival time was 221 days. These results suggest that weekly PTX has modest activity with a favorable toxicity profile in patients with advanced/recurrent gastric cancer, and so this regimen may thus might be recommended in an outpatient treatment setting.     

Combination of folinic acid, 5-fluorouracil bolus and infusion, and cisplatin (LV5FU2-P regimen) in patients with advanced gastric or gastroesophageal junction carcinoma.

BACKGROUND: Combination chemotherapy with continuous 5-fluorouracil (5-FU) and cisplatin in a monthly regimen is one of the standard treatments for advanced gastric carcinoma. This study evaluated the new LV5FU2-P regimen, designed to improve efficacy and tolerance of the 5-FU plus cisplatin combination. PATIENTS AND METHODS: Forty-three patients with advanced or metastatic gastroesophageal junction or gastric carcinoma were prospectively included in the study. They were treated every 14 days with cisplatin 50 mg/m(2) on day 2 plus folinic acid 200 mg/m(2)/day as a 2-h intravenous (i.v.) infusion on days 1 and 2, plus bolus 5-FU 400 mg/m(2)/day on days 1 and 2, plus continuous 5-FU 600 mg/m(2)/day as a 22-h i.v. infusion on days 1 and 2. Ten patients received a simplified regimen (folinic acid 40 mg/m(2) day 1 + bolus 5-FU 400 mg/m(2) day 1 + continuous 5-FU 2400 mg/m(2) on days 1 and 2 with cisplatin 50 mg/m(2) on day 2). RESULTS: All the patients were assessable for response and 42 for toxicity. One patient achieved a complete response and 15 a partial response, for an overall response rate of 37.2% [95% confidence interval (CI) 22.1% to 52.3%]. The median progression-free survival was 7.2 months (95% CI 5.4-10.9) and the overall survival was 13.3 months (95% CI 10.1-16.4). There were no treatment-related deaths. Hematological and gastrointestinal toxicities were the most common severe toxicities. CONCLUSIONS: LV5FU2-P is an active and well tolerated regimen in the treatment of advanced gastroesophageal junction or gastric carcinomas. It warrants evaluation comparatively with other active regimens.     

Weekly etoposide, epirubicin, cisplatin, 5-fluorouracil and leucovorin: an effective chemotherapy in advanced gastric cancer.

In order to optimize the therapeutic index of combining etoposide, epirubicin, cisplatin, 5-fluorouracil (5-FU), leucovorin (EEPFL) chemotherapy in the treatment of advanced gastric cancer, a trial of a novel schedule of weekly administration was conducted. Weekly EEPFL treatment consisted of a concomitant boost of etoposide 40 mg m(-2) i.v. over 30 min, epirubicin 10 mg m(-2) i.v. over 5 min to a backbone regimen, weekly PFL chemotherapy with cisplatin 25 mg m(-2), 5-FU 2200 mg m(-2), leucovorin 120 mg m(-2) given simultaneously by 24-h i.v. infusion. Response, survival and toxicity were evaluated. Forty-two patients were studied. Median age was 69 (range 31-84) years. Twenty-six per cent of patients showed complete response and 45% partial response. The overall response rate was 71% (95% confidence interval 58-84%). For a total of 507 weekly EEPFL cycles delivered, the incidence of grade 4 leucopenia was 1% of cycles. One patient died of neutropenia septicaemia. There was no other grade 4 toxicity. Grade 3 and 2 leucopenia occurred in 7% and 14% of cycles. The incidence of grade 3 and 2 mucositis was 1% and 3% of cycles. Grade 3 and 2 diarrhoea occurred in 0.4% and 1.6% of cycles. Overall median survival was 10 months (range 3-41+ months). Weekly EEPFL chemotherapy is an effective regimen with tolerable toxicities in the treatment of advanced gastric cancer. A randomized controlled clinical trial to formally assess the efficacy and benefit of EEPFL chemotherapy is under way.     

Sequential chemotherapy with cisplatin, leucovorin, and 5-fluorouracil followed by docetaxel in previously untreated patients with metastatic gastric cancer: a phase II study

Background

The combination of docetaxel, cisplatin, and 5-fluorouracil (5-FU) has demonstrated a survival advantage over cisplatin and 5-FU, but with substantial hematological toxicity. We aimed to evaluate the efficacy and toxicity of a sequential regimen with cisplatin, leucovorin, and 5-FU (PLF) followed by docetaxel in metastatic gastric cancer patients.

Methods

Treatment consisted of 4 cycles of biweekly PLF (cisplatin 50?mg/m² as a 30-min infusion on day 1, leucovorin 200?mg/m² in a 2-h infusion, and 5-FU 2,800?mg/m² in a 48-h continuous infusion starting on day 1) followed, in cases of response or stable disease, by 3 cycles of docetaxel (75?mg/m², every 3?weeks).

Results

Thirty-four patients were enrolled, with an average age of 64?years (range 34–69). The main cumulative grade 3–4 toxicities were: neutropenia (38.2%), febrile neutropenia (11.8%), and fatigue (14.7%). After the planned 7 cycles of treatment, the overall response rate was 38.2% (95% confidence interval [CI] 21.9–54.6), with 3 complete and 10 partial responses. Median progression-free survival and overall survival were 4.8 and 10.6?months, respectively.

Conclusions

For patients with metastatic gastric cancer, the sequential administration of cisplatin, leucovorin, 5-FU, and docetaxel may be an effective palliative option and offers a far more favorable toxicity profile than the simultaneous use of docetaxel, cisplatin, and 5-FU.