Weekly chemotherapy with cisplatin,vincristine, doxorubicin,and etoposide is an effective treatment for advanced thymic carcinoma

BACKGROUND: Thymic carcinoma is a rare neoplasm that often disseminates or metastasizes. The role of chemotherapy in treating this malignancy is unclear. The purpose of the current study was to determine the efficacy and tolerability of a weekly chemotherapy regimen consisting of cisplatin, vincristine, doxorubicin, and etoposide (CODE) for the treatment of advanced thymic carcinoma. METHODS: The authors retrospectively reviewed 18 patients with thymic carcinoma who were treated between 1996 and 2002. Twelve of these patients had unresectable advanced diseases and received weekly chemotherapy according to the CODE regimen. The CODE regimen consisted of cisplatin (25 mg/m(2), intravenously [i.v.]; weekly administration), vincristine (1 mg/m(2), i.v.; administered during Weeks 1, 2, 4, 6, and 8), doxorubicin (40 mg/m(2), i.v.; administered during Weeks 1, 3, 5, 7, and 9), and etoposide (80 mg/m(2), i.v.; administered for 3 days during Weeks 1, 3, 5, 7, and 9). RESULTS: The responses of all 12 patients to the CODE regimen were assessed. A partial response was achieved in 5 patients, and the overall response rate was 42%. Only one patient experienced disease progression. The median progression-free survival period was 5.6 months (range, 2-39 months). The overall survival period ranged from 6 to 79 months, with a median survival period of 46 months. Based on the Kaplan-Meier method, the estimated 1-year and 2-year survival rates were 80% and 58%, respectively. The most common side effects were hematologic toxicities, and only mild nonhematologic toxicities were experienced. CONCLUSIONS: Weekly chemotherapy treatments according to the CODE regimen were effective and tolerated by patients with advanced thymic carcinoma.     

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.     

Phase I trial of concurrent thoracic radiation and continuous infusion cisplatin and etoposide in stage III non-small cell lung cancer.

OBJECTIVE: Although combined modality therapy appears to be superior to radiotherapy alone for the treatment of locally advanced non-small cell lung cancer (NSCLC), the optimal treatment regimen has not been determined. We designed this trial to determine the maximal tolerated doses (MTD) of continuous intravenous infusion (CI) cisplatin and etoposide that could be administered concurrently with thoracic irradiation. METHODS: 19 patients with stage IIIA or IIIB NSCLC were treated at three different dose levels of CI cisplatin and etoposide with concurrent single daily fraction thoracic radiotherapy to 4500 cGy. This chemoradiotherapy phase of treatment was followed by a 1500-2000 cGy radiotherapy boost and three cycles of standard intermittent bolus cisplatin 80 mg/m2 i.v. on day 1 and etoposide 80 mg/m2 i.v. on days 1, 2 and 3. RESULTS: The MTD of CI chemotherapy was determined to be cisplatin 5 mg/m2/day plus etoposide 18 mg/m2/day for 5 days per week over 5 weeks along with thoracic irradiation. Overall, 37% of patients required breaks in the chemoradiotherapy course and 32% required attenuation of the planned duration of CI chemotherapy. Only 42% of patients received all three planned cycles of bolus chemotherapy and 16% received < 6000 cGy of thoracic irradiation. The major toxicities during concurrent chemoradiotherapy were grade 3-4 esophagitis (42%) and myelosuppression (47%). Subsequent chemotherapy was complicated by grade 3-4 myelosuppression in 38% of patients. An objective response was documented in 58% of patients (CR 11%, PR 47%). Median survival was 18 months with 2- and 5-year survival rates of 42 and 11%, respectively. CONCLUSIONS: These results demonstrate that CI cisplatin and etoposide can be administered safely to patients with locally advanced NSCLC, and that such potentially radiosensitizing strategies deserve further evaluation in this 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.     

Cisplatin, fluorouracil, and high-dose leucovorin for recurrent or metastatic head and neck cancer

We added high-dose oral leucovorin to the combination of cisplatin and fluorouracil (5-FU) to assess the efficacy of this regimen in the treatment of patients with head and neck cancer. Cisplatin, 100 mg/m2, was followed by a 5-FU continuous infusion at 600 mg/m2/d for five days. Leucovorin, 50 mg/m2, was administered at the start of cisplatin and every six hours throughout the duration of the 5-FU infusion. The dose of 5-FU was escalated to 800 mg/m2 and 1,000 mg/m2 according to observed toxicity. In a second phase of the study, the dose of leucovorin was escalated to 50 mg/m2 every four hours. A total of 25 patients were registered: 23 had recurrent disease after extensive prior treatment; and two had newly diagnosed metastatic disease. The maximally tolerated dose of 5-FU was 800 mg/m2/d with leucovorin administered every six hours. Toxicities at that level included mild to moderate myelosuppression and dose-limiting mucositis in the previously irradiated field. Identical toxicities were observed when administering 800 mg/m2/d of 5-FU with leucovorin every four hours. Eighteen patients were evaluated for response: one had a pathologic complete response; nine had a partial response (including four who received prior cisplatin and 5-FU as induction chemotherapy); and eight patients failed to respond. The mean peak and trough plasma leucovorin concentrations were 2.61 (+/- 1.07) mumol/L and 2.46 (+/- 0.95) mumol/L with administration of the drug every six hours, and 2.75 (+/- 2.15) mumol/L and 2.52 (+/- 1.48) mumol/L with administration every four hours. We conclude that the combination of cisplatin, 5-FU, and leucovorin has activity in the treatment of recurrent head and neck cancer. The maximally tolerated dose of 5-FU in this study was 800 mg/m2/d, with mucositis in previously irradiated sites being dose-limiting. Plasma leucovorin concentrations exceeding 1 mumol/L are achieved following oral administration of this drug.     

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.     

Infusional fluorouracil,etoposide, and cisplatin (FEP) in advanced and relapsed gastric cancer

We evaluated the efficacy and tolerability of a combination chemotherapy including infusional fluorouracil (5-FU), etoposide, and cisplatin (FEP) in 89 patients with advanced/relapsed gastric cancer. Primary endpoints were progression-free and overall survival. Secondary endpoints were response rates, response duration, and toxicity. The treatment schedule was as follows: 5-FU 1,000 mg/m2 and etoposide 100 mg/m2 were administered on 3 consecutive days and cisplatin at 80 mg/m2 was administered on day 2, and repeated every 3 weeks. The median times to progression and overall survival were 4 and 8 months, respectively. One-year progression-free and overall survival rates were 10% and 33%, respectively. The overall response rate for 25 eligible patients with measurable disease was 20% (5/25, complete response 2, partial response 3) with median response duration of 7 months. Median actual dose intensities of 5-FU, etoposide, and cisplatin were 700 mg/m2/wk, 70 mg/m2/wk, and 21 mg/m2/wk, respectively. Median relative dose intensities of 5-FU, etoposide, and cisplatin were 0.70, 0.70, and 0.63, respectively. In conclusion, the FEP regimen was found to produce therapeutic results similar to those of other combination chemotherapeutic studies and to have an acceptable toxicity. This regimen could be used as one of the options for advanced gastric cancer chemotherapy in patients unsuitable for doxorubicin-based regimens.     

Phase II study with a combination of epirubicin, cisplatin, UFT, and leucovorin in advanced hepatocellular carcinoma

Purpose: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Because HCC usually presents as an advanced disease and occurs in the background of liver cirrhosis, most patients are not suitable for treatment with curative intent, thus effective systemic chemotherapy is required. However, the outcome of systemic chemotherapy has been disappointing in advanced HCC. This study was conducted to test the efficacy and toxicity of the combined regimen of epirubicin, cisplatin, and UFT moderated by leucovorin in advanced or recurrent HCC. Patients and methods: All 53 patients received epirubicin (50 mg/m² i.v.) on day 1 and cisplatin (60 mg/m² i.v.) after epirubicin administration. Oral UFT 400–600 mg/day, determined by body surface area, and leucovorin 75 mg/day were administered for 21 consecutive days, followed by a 7-day drug free interval. Results: Nine had a partial response, representing 16.9% of response rate (95% confidence interval rate; 7.0–26.8%) with median response duration of 17.1 weeks (95% CI; 5.0–29.3 weeks, range; 7.1–51.7 weeks). Fifteen patients had stable disease and the disease progressed in 26 patients. The median overall survival for the patients was 24.6 weeks (95% CI; 17.3–31.9 weeks, range; 3.0–131.3 weeks). The main toxicities were hematologic toxicities including neutropenia, which reached grade 3/4 in 17 patients (38.5%), and grade 3 or 4 thrombocytopenia in five patients (9.4%). Conclusion: The combination of epirubicin, cisplatin, and UFT moderated by leucovorin showed modest anti-tumor activity with relatively tolerable toxicities. However, a randomized phase III trial based on this regimen is warranted to clarify its survival benefit in patients with advanced HCC. Contract grant sponsor: Brain Korea 21 Project in 2002 and Korea Health 21 R &D Project, Ministry of Health & Welfare, Republic of Korea: 01-PG3-PG6-01GN07-0004.     

Mitomycin C, 5-fluorouracil, leucovorin, and oxaliplatin as a salvage therapy for patients with cisplatin-resistant advanced gastric cancer: a phase I dose escalation trial

BACKGROUND: This study aimed at evaluating the feasibility and toxicity of a salvage therapy with mitomycin C (MMC), 5-fluorouracil (5-FU), leucovorin, and oxaliplatin in patients with cisplatin-resistant advanced gastric cancer. METHODS: A 3-patient cohort dose-escalating study design was used. The patients received FLO: oxaliplatin 85 mg/m2, 5-FU 2,600 mg/m2 (24 h), leucovorin 200 mg/m2 on days 1, 15, and 29 plus MMC on day 1 (FLOM). The MMC dose was escalated from 6 to 12 mg/m2 in 2- mg/m2 steps. Cycles were repeated every 6 weeks. RESULTS: Twenty patients were enrolled in 4 treatment cohorts. The treatment was well tolerated with grade 3 or 4 nonhematological toxicities affecting less than 5% of patients. Grade 3 or 4 neutropenia, anemia, and thrombocytopenia were observed in 9 (45%), 7 (35%), and 5 (25%) of 20 patients, respectively. Mild but prolonged thrombocytopenia was dose limiting, requiring treatment discontinuation or a treatment delay >or=2 weeks in 8 (40%) of 20 patients. MMC 10 mg/m2 every 6 weeks was considered as the optimal dose in combination with FLO. Objective responses were observed in 7 (35%) of 20 patients, and 7 further patients (35%) had stable disease. Median time to progression and overall survival were 4.1 and 8 months, respectively. CONCLUSIONS: Prolonged cumulative myelotoxicity was dose limiting in the therapy with MMC, 5-FU, and oxaliplatin. This combination chemotherapy seems to overcome cisplatin resistance in patients with advanced gastric cancer.     

Vinorelbine, ifosfamide, and cisplatin combination as salvage chemotherapy in advanced non-small cell lung cancer

BACKGROUND: Platinum-based chemotherapy improves survival and quality of life as compared with the best supportive care alone in advanced non-small cell lung cancer. In addition, several recent studies using new drugs such as docetaxel have demonstrated that second-line chemotherapy may be of value. METHODS: We studied the efficacy of combination treatment with vinorelbine, ifosfamide, and cisplatin (NIP) as salvage chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). From March 1998 to December 1999, 44 previously treated patients (etoposide/cisplatin (EP): 36, EP--> taxane/cisplatin: 8) were treated with a chemotherapy regimen consisting of vinorelbine (25 mg/m(2) i.v. on days 1, 15 and 12.5 mg/m(2) i.v. on day 8), ifosfamide (3 g/m(2) i.v. on day 1 with mesna) and cisplatin (60 mg/m(2) i.v. on day 1). The cycles were repeated every 4 weeks. RESULTS: All patients were evaluable for response. The median follow-up duration was 19.1 months (range, 4.4-28.3 months). The objective response rate was 27.3% (95% CI, 14.1%-40.5%) with one complete response and 11 partial responses. The median response duration was 4.1 months (range, 1.5-13 months). The median time to progression was 2.9 months (range, 0.7-15.3 months). The main toxicity was hematologic in the 138 evaluable courses, granulocytopenia (>or=grade III) and anemia (>or=grade III) were observed in 3.6% and 0.7% of the patients, respectively. Non-hematologic toxicities were minor and easily controlled. Four episodes of febrile neutropenia were reported. There were no treatment-related deaths. CONCLUSION: In this study, the combination of vinorelbine, ifosfamide and cisplatin showed a significant efficacy with acceptable toxicities as salvage chemotherapy in previously treated advanced NSCLC patients.     

Etoposide,leucovorin (LV) and 5-fluorouracil (5-FU) in 5-FU+LV pre-treated patients with advanced colorectal cancer

In the present study, we evaluated the efficacy and safety of the weekly combination of etoposide, leucovorin (LV) and 5-fluorouracil (5-FU) when administered as second-line chemotherapy in patients with relapsed/refractory advanced colorectal cancer (ACC), previously treated with weekly LV+5-FU. Etoposide was administered at 3 different dose levels (DLs), in 3 groups of 20 patients each (total: 60); DL-I: etoposide 80 mg/m2, DL-II: etoposide 120 mg/m2, and DL-III: etoposide 180 mg/m2, in 45 min i.v. infusion, and followed in all levels by LV 100 mg/m2 i.v. over 1 hour and 5-FU 500 mg/m2 i.v. bolus. Treatment was administered weekly until disease progression or unacceptable toxicity. No patients at DL-I responded, while 2 patients at DL-II and 3 at DL-III had a partial response (PR). Stable disease (SD) rates were as follows; at DL-I: 2, DL-II: 8 and DL-III: 9. More patients in DL-I progressed (n = 19) compared to DL-II (n=10) and DL-II (n = 8) (p < 0.0007). Time to progression was for DL-I, -II, -III: 17, 15, and 14 weeks, respectively. Median survival was DL-I, -II, -III: 30, 30, and 32.5 weeks, respectively. Toxicity consisted mainly of neutropenia, diarrhea and mucositis at all DLs, and was significantly more severe in DL-III. No difference was noted in responses between DL-II and DL-III. The authors conclude that the combination of etoposide with LV+5-FU has limited activity when administered after failure of weekly LV+5-FU in patients with ACC and should not be recommended for further evaluation.     

奥沙利铂联合氟尿嘧啶２周方案与３周方案一线治疗进展期胃癌的比较研究

目的　比较奥沙利铂（Ｌ-ＯＨＰ）联合氟尿嘧啶／亚叶酸钙（５-ＦＵ／ＣＦ）的２周方案与３周方案一线治疗进展期胃癌的临床疗效及不良反应。方法　８８例进展期胃癌患者,其中２周方案组４８例,具体方案：Ｌ-ＯＨＰ８５ｍｇ／ｍ２静脉滴注２小时,第１天;ＣＦ２００ｍｇ／ｍ２静脉滴注２小时,第１、２天;５-ＦＵ４００ｍｇ／ｍ２静脉推注,６００ｍｇ／ｍ２持续静脉滴注２２小时,第１、２天,２周重复１次,２次计为ｌ周期,２周期评价疗效。３周方案组４０例,具体方案：Ｌ-ＯＨＰ１３０ｍｇ／ｍ２ 静脉滴注２小时,第１天;ＣＦ２００ｍｇ／ｍ２静脉滴注２小时,第１～５天;５-ＦＵ３７５ｍｇ／ｍ２静脉滴注６小时,第１～５天,３周重复１次,每次计为１周期,２周期评价疗效。结果　全组均可评价疗效,２周方案及３周方案的ＲＲ分别为４７.９％和４５.０％（Ｐ＞０.0５）,中位肿瘤进展时间（ＴＴＰ）分别为９.０个月和６.６个月（Ｐ＜０.０５）,中位总生存期（ＯＳ）分别为１３.６个月和１０.０个月（Ｐ＜０.０５）。两组主要毒副反应为消化道反应,神经系统、血液学毒性和脱发,发生率近似。结论　Ｌ-ＯＨＰ联合５-ＦＵ／ＬＶ２周方案与３周方案的近期疗效和安全性无差异,但远期疗效较优,值得临床进一步研究。     

Phase II trial of epirubicin, cisplatin, oral uracil and tegafur, and leucovorin in patients with advanced gastric carcinoma.

BACKGROUND: The results of chemotherapy for patients with gastric carcinoma generally have been modest, although regimens developed more recently have produced higher response rates. One such regimen is epirubicin, cisplatin, and protracted infusion of 5-fluorouracil (ECF). The advantage of a long-term oral administration of uracil and tegafur (UFT) is that this treatment may be used to mimic the protracted infusion of 5-fluorouracil (5-FU). In addition, UFT treatment combined with leucovorin had a favorable activity and tolerable toxicity in patients with advanced gastric carcinoma. Instead of the inconvenience of an infusion pump and intravenous catheter for the protracted infusion of 5-FU, the authors administered UFT plus leucovorin in an ECF regimen for the treatment of patients with advanced gastric carcinoma. METHODS: Fifty-two patients with advanced gastric carcinoma received epirubicin, cisplatin, and oral UFT plus leucovorin. Epirubicin 50 mg/m(2) and cisplatin 60 mg/m(2) were administered on Day 1 by intravenous injection. Tegafur and uracil 360 mg/m(2)/day orally was administered in conjunction with leucovorin administered at a fixed dose of 45 mg/day orally in divided daily doses for 21 days followed by a 7-day rest period. These courses were repeated every 4 weeks. The median age of the patients was 59 years with a median World Health Organization performance status of 1. Patients received a median of five courses of treatment (range, 1-10). RESULTS: Among the 47 patients evaluated, three patients achieved complete response, and 24 patients had partial responses, for an overall response rate of 57.5% (95% confidence interval, 71.5-43.3%). Stable disease was reported in 11 patients (23.4%), and another 9 patients (19.1%) showed disease progression. The median duration of survival was 15 months (range, 2-33+). The main toxicity was nausea/vomiting and neutropenia. Significant toxicity (modified National Cancer Institute common toxicity Grade 3 or 4) included neutropenia in 22 patients (42%), nausea in 14(27%), vomiting in 9 (18%), oral mucositis in 3 (6%), and diarrhea in 3 (6%) patients. CONCLUSIONS: The authors conclude that epirubicin, cisplatin, and oral UFT plus leucovorin, a convenient regimen, has a significant activity and tolerable toxicities in patients with gastric carcinoma.     

5-FU加CF双周疗法联合腹腔化疗治疗晚期胃癌临床观察

目的:探讨5-氟尿嘧啶(5-FU) 醛氢叶酸(CF)双周疗法联合顺铂(DDP)、依托泊苷(Vp-16)腹腔化疗治疗晚期胃癌的疗效及不良反应。方法:103例患者按数字随机法分两组。观察组54例:CF200mg/m2,静脉滴入,后经留置中心静脉导管48h持续灌注高浓度5-FU3g/m2,腹腔化疗DDP80mg/m2、Vp-16200mg/m2,每2周重复。对照组49例:CF200mg/d、5-FU500mg/(m2·d),静脉滴入,d1~d5,DDP20mg/(m2·d)、Vp-1670mg/(m2·d),静脉滴入,d1~d4,每3周重复。结果:观察组和对照组有效率分别为64·8%和44·9%,KPS评分增高率分别为74·1%和53·1%,中位生存期分别为13和8·5个月,1年生存率分别为48·1%、38·8%,有效率及KPS评分增高率差异有统计学意义,P<0·05。两组骨髓毒性及消化道反应相似,P>0·05,观察组静脉炎、口腔黏膜炎明显减轻。结论:5-FU CF双周疗法联合腹腔化疗对晚期胃癌有效率高,不良反应较轻,生存质量提高。     

Phase II study of irinotecan plus leucovorin and bolus 5-fluorouracil as first- or second-line chemotherapy in patients with advanced gastric or esophageal-gastric junction adenocarcinoma

The aim of this study was to evaluate the activity and safety of 5-fluorouracil (5-FU)/leucovorin (LV) and irinotecan as first- or second-line treatment in patients with advanced gastric adenocarcinoma. Treatment consisted of irinotecan 80 mg/m(2) intravenously (i.v.), followed by LV 200 mg/m(2) (i.v.) and 5-FU 450 mg/m(2) as an i.v. bolus, administered weekly for 6 weeks, followed by a 2-week rest period. Thirty-one patients (23 chemo-na?ve, 8 chemo-exposed) were enrolled. The overall response rate was 22.6% and the disease control rate was 38.7%. Among the patients who received the regimen as first-line treatment, objective response rate was 30.4% and the disease control rate was 52.1%. However, progression of the disease was recorded in all the patients receiving the combination as second-line chemotherapy. The median time to disease progression (TTP) was 4 months and the median duration of survival was 7 months. The median TTP was 6 months for patients treated with first-line chemotherapy and 2.5 for those who received study treatment as second line. Furthermore, the median survival duration was 8 months and 6 months, respectively. The most frequent grade 3 toxicity was febrile neutropenia. Grade 3 non-hematological toxicities were rare. There were no treatment-related deaths. The combination of 5-FU/LV and irinotecan as first-line treatment was found to be well tolerated and effective in patients with advanced gastric cancer. Further investigation would be worthwhile, particularly in elderly or debilitated patients who cannot tolerate aggressive chemotherapy.     

Phase II trial of 5-fluorouracil/leucovorin/gemcitabine/cisplatin as second-line treatment in patients with metastatic or recurrent colorectal carcinoma: a cancer therapeutics research group study

BACKGROUND: Second-line treatment of relapsed or metastatic colorectal cancer (CRC) after failure of treatment with a fluoropyrimidine is composed of oxaliplatin in combination with a fluoropyrimidine or an irinotecan-containing regimen. Cisplatin and gemcitabine are synergistic in preclinical studies, as is 5-fluorouracil (5-FU) combined with either agent. Fixed-rate infusional gemcitabine is more effective than bolus administration in animal models. PATIENTS AND METHODS: A 2-stage phase II trial was conducted to assess the efficacy (the primary endpoint was response rate) and safety of a regimen consisting of 5-FU 400 mg/m(2) as an intravenous bolus at the middle of a 60-minute infusion of leucovorin 100 mg/m(2), followed by gemcitabine 800 mg/m(2) over 80 minutes, and cisplatin 20 mg/m(2) over 15 minutes. Treatment was repeated weekly for 3 weeks followed by a 1-week rest. Patients with advanced CRC were eligible if they had experienced treatment failure with fluoropyrimidine-based therapy. RESULTS: Nineteen patients were enrolled. The median age was 60 years; 15 patients were men and 4 were women. Twelve patients had colon cancer and 7 had rectal cancer. Sites of metastasis were as follows: liver (n = 10), lung (n = 8), skin (n = 1), and non-regional lymph nodes (n = 1). All patients had an Eastern Cooperative Oncology Group performance status of 0/1. A total of 44 cycles of chemotherapy were delivered (median, 2 cycles; range, 1-5 cycles). One patient exhibited a partial response (5%), 8 had stable disease (42%), and 5 experienced disease progression (26%); another 5 patients were nonevaluable (26%). The median time to progression was 8 weeks and median survival was 36 weeks. Grade 3/4 toxicities were as follows: diarrhea (n = 1), dyspnea (n = 1), pneumonia (n = 1), neutropenia (n = 2), and thrombocytopenia (n = 1). CONCLUSION: Despite acceptable toxicity and a reasonable overall survival, the combination of 5-FU/leucovorin/gemcitabine/cisplatin does not seem to improve current standard therapy in the second-line treatment of patients with CRC in whom a first-line fluoropyrimidine-containing regimen has failed.     

Irinotecan,oxaliplatin, and 5-fluorouracil/leucovorin combination chemotherapy in advanced colorectal carcinoma: a phase II study

The purpose of this study was to evaluate the efficacy and tolerance of a combination of irinotecan, oxaliplatin, and 5-fluorouracil (5-FU)/leucovorin in advanced colorectal cancer (ACC). Twenty-six consecutive patients with ACC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of oxaliplatin (120 mg/m2 intravenously [i.v.] for 2 hours) on day 1, irinotecan (250 mg/m2 i.v. for 90 minutes) on day 1, and 5-FU (2600 mg/m2 plus leucovorin 500 mg/m2 i.v. in a 24-hour infusion) on day 1 and 15, every 4 weeks. Five of the patients (19.2%) had shown previous chemoresistance. One hundred sixty-two cycles were administered (median, 6; range, 3-13 cycles). All patients were evaluated for toxicity; 23 were evaluable for response. According to intention-to-treat, the overall response rate was 69.2% (18 patients; 95% CI: 48.2%-85.7%), including 3 complete remissions (11.5%). Four additional patients (15.3%) had stable disease, and only 1 (3.8%) progressed. Major toxicities were neutropenia and diarrhea. Grade 3 neutropenia occurred in 9 patients (34.6%), and grade 4 occurred in 1 patient (3.8%). Grade 3 diarrhea occurred in 8 patients (30.7%) and grade 4 in 1 patient (3.8%). Other toxicities were mild. After a median follow-up of 15.5 months, the median progression-free survival was 14 months. Seventeen patients (65.4%) are still alive, and the median overall survival has not been reached yet. This combination of irinotecan, oxaliplatin, and 5-FU/leucovorin is fairly well tolerated and shows promising activity in ACC. This treatment merits further comparison with other combination regimens.     

Treatment of patients with advanced colorectal carcinomas with fluorouracil alone, high-dose leucovorin plus fluorouracil, or sequential methotrexate, fluorouracil, and leucovorin: a randomized trial of the Northern California Oncology Group

We compared the effectiveness of fluorouracil (5-FU) alone (arm A), high-dose leucovorin plus 5-FU (arm B), and sequential methotrexate, 5-FU, and leucovorin (arm C) for treatment of patients with advanced colorectal carcinomas who had not received prior chemotherapy. Arm A consisted of infusions of 5-FU at 12 mg/kg/d intravenously (IV) for 5 days followed by weekly infusions of 5-FU at 15 mg/kg; arm B consisted of leucovorin infusions at 200 mg/m2/d IV plus infusions of 5-FU at 400 mg/m2/d IV on days 1 through 5 of a 28-day cycle; arm C consisted of methotrexate at 50 mg/m2 orally every 6 hours for five doses followed by infusions of 5-FU, 500 mg/m2 IV, and leucovorin, 10 mg/m2 orally, every 6 hours for five doses every other week. A total of 265 patients were entered into the trial, of whom 249 (94%) were fully evaluable. The objective response rate (complete [CR] plus partial [PR] responses) was 17.3% on arm A, 18.8% on arm B, and 19.8% on arm C (log-rank test, P greater than .4). The median time to failure was 138 days on arm A, 166 days on arm B, and 182 days on arm C (log-rank test, P values of arm A v B = .06; arm A v arm C = .04). Median survival was 345 days on arm A, 324 days on arm B, and 356 days on arm C (log-rank test, P greater than .4). Treatment with 5-FU alone was significantly more dose intensive and more toxic than either of the experimental combinations. The rates of grade 3 or greater nonhematologic toxicity were 42.3% on arm A, 24.3% on arm B, and 14.3% on arm C. Hematologic toxicity was milder but had the same pattern. This study indicates that these regimens of high-dose leucovorin plus 5-FU and sequential methotrexate, 5-FU, and leucovorin are not more effective than is 5-FU alone for treatment of patients with colorectal carcinomas when 5-FU is administered at high-dose intensity.     

Salvage chemotherapy with irinotecan, 5-fluorouracil and leucovorin for taxane- and cisplatin-refractory, metastatic gastric cancer

We performed a phase II study of combination chemotherapy with irinotecan, 5-fluorouracil (5-FU) and leucovorin in metastatic gastric cancer patients who were previously treated with taxane and cisplatin, to evaluate the antitumour activity and toxicity of the combination chemotherapy. The metastatic gastric adenocarcinoma patients who were previously treated with taxane and cisplatin combination as first line, and had at least one measurable lesion, 0-2 ECOG performance status and adequate organ functions, were considered eligible. They received irinotecan (150 mg m(-2), day 1) and leucovorin (100 mg m(-2), day 1), followed by continuous infusion of 5-FU (1000 mg m(-2) day(-1), days 1 and 2) every 2 weeks. Treatment was continued until progression of disease was observed. In all, 64 patients were treated with this combination chemotherapy. The median age of the patients was 55 years (range, 33-74 years), and the median ECOG performance status was 1 (0-1, 61 (95%)). Out of 64 patients, 57 were assessable for response. Among 57 assessable patients, no complete response and 12 partial responses were observed (overall response rate, 21%; 95% confidence interval (CI), 10-32%). Stable disease was observed in 14 patients (25%) and progressive disease in 31 patients (54%). The median time to progression was 2.5 months (95% CI, 1.6-3.4) and the median overall survival since the start of the second-line modified FOLFIRI was 7.6 months (95% CI, 6.5-8.7). Grade 3-4 haematologic toxicities included neutropenia in seven patients (11%) and thrombocytopenia in five patients (8%). Grade 3-4 nonhaematologic toxicities included diarrhoea in two patients (3%) and vomiting in two patients (3%). There were no treatment-related deaths. The combination of irinotecan, 5-FU and leucovorin showed moderate activity and favourable toxicity profile as a second-line treatment in metastatic gastric cancer patients, who were previously treated with taxane and cisplatin.     

Efficacy and toxicity of intra-arterial cisplatin and etoposide for advanced hepatocellular carcinoma

OBJECTIVE: To analyze the results of an intra-arterially delivered combination chemotherapy in a group of patients with regionally advanced hepatocellular carcinoma (HCC). METHODS: 26 patients with proven locally advanced HCC treated with hepatic artery infusion of cisplatin (20 mg/m(2), days 1-5) and etoposide (75 mg/m(2), days 1-5) every 4 weeks were retrospectively studied. RESULTS: In an intention-to-treat analysis, overall and complete response rates were 38 and 7%, respectively. Median duration of response was 5 months. Median survival time was 10 months and survival rates at 6, 12 and 24 months were 53, 33 and 24%, respectively. Survival was significantly longer for responders than for non-responders (median: 13 and 3 months, respectively). There were 4 treatment-related deaths among cirrhotics. CONCLUSIONS: Intra-arterial chemotherapy using cisplatin and etoposide seems to have some anti-tumor effect against advanced HCC, although a high rate of life- threatening complications precludes the indication of this regimen at least for patients with non-compensated cirrhosis.