FOLFIRI方案二线治疗23例晚期胃癌临床观察

目的：评价FOLFIRI方案二线治疗晚期胃癌的疗效及不良反应。方法23例晚期胃癌患者采用伊立替康150 mg/m^2,静脉滴注90 min, d1；甲酰四氢叶酸（CF）200 mg/m^2,静脉滴注2 h, d1-2；5-FU 2400 mg/m^2静脉滴注46 h,每2周重复,3周期后评定疗效。结果完全缓解（CR）0例,部分缓解（PR）8例,稳定（SD）4例,进展（PD）11例,总有效率为34.7%,疾病控制率52.2%。中位PFS为3.8个月,中位OS为14.1个月,1年生存率39.1%,常见的不良反应为白细胞减少、腹泻和恶心呕吐。结论 FOLFIRI方案二线治疗晚期胃癌具有较高的疗效,不良反应可耐受且可控制。     

A phase I and pharmacokinetic study of lapatinib in combination with infusional 5-fluorouracil, leucovorin and irinotecan.

BACKGROUND: This study determined the optimally tolerated regimen (OTR) of oral lapatinib administered in combination with infusional 5-fluorouracil (5-FU), leucovorin and irinotecan (FOLFIRI) and assessed the safety, tolerability and pharmacokinetics of the combination. PATIENTS AND METHODS: Twenty-five patients were enrolled; 12 patients were treated at three dose levels to determine OTR; then 13 patients were treated at OTR to evaluate the pharmacokinetics of the combination. RESULTS: The 2-weekly OTR comprised lapatinib 1250 mg/day with irinotecan 108 mg/m(2) (day 1) and leucovorin 200 mg/m(2), 5-FU bolus 240 mg/m(2) and 5-FU infusion 360 mg/m(2) (days 1 and 2); doses of 5-FU and irinotecan represent a 40% reduction in dose compared to conventional FOLFIRI. Dose-limiting toxicities were grade 3 diarrhoea and grade 4 neutropenia. Co-administration of lapatinib increased the area under the plasma concentration-time curve of SN-38, the active metabolite of irinotecan, by an average of 41%; no other pharmacokinetic interactions were observed. Of 19 patients evaluable for disease response assessment, four patients had partial response and nine patients had stable disease. CONCLUSION: The combination of lapatinib and FOLFIRI is safe and demonstrates clinical activity; the documented PK interaction can effectively be compensated by lowering the doses of 5-FU and irinotecan. This regime may be further tested in a phase II trial.     

SELDI技术预测FOLFIRI方案治疗结肠癌疗效敏感性的应用研究

目的：应用SELDI 技术发现预测FOLFIRI 方案治疗晚期结肠癌患者疗效敏感性的界定指纹,探索新的用药指征.方法：选择12例行FOLFIRI 方案化疗,并有可观察疗效的晚期结肠癌术后患者,应用表面增强飞行时间质谱（SELDI-TOF-MS） 技术在化疗前对患者的血清样本进行检测,根据RECIST 实体肿瘤疗效评价标准将FOLFIRI 方案治疗1 疗程（3 周期） 后2 周~3 个月内的患者分成稳定组（SD） 和无效组（PD）.应用ProteinChip 3.2.0 和Biomarker Wizard 3.1 软件分析两组之间有显著差异的指纹（ 峰型及丰度） 并进行比较.结果：术后稳定组与无效组相比有3 个蛋白质峰有显著差异性,M/Z 分别为1372、1698、1865,与稳定组相比,无效组上调的峰M/Z 为1372 和1698,下调的峰M/Z 为1865.结论：应用SELDI 技术可以获得预测FOLFIRI 方案治疗结肠癌疗效敏感性的标识指纹,其M/Z 为：1372±50H＋、1698±50H＋、1865±50H＋.其中M/Z：1372±50H＋ 丰度〈10、1698±50H＋ 丰度〈5、1865±50H＋ 丰度〉10 为预计FOLFIRI 方案治疗结肠癌可获得稳定的标识指纹;其M/Z：1372±50H＋ 丰度≥ 10、1698±50H＋ 丰度≥ 5、1865±50H＋ 丰度≤ 10 为预计FOLFIRI 方案治疗结肠癌无效的标识指纹.     

Anti-angiogenic therapies for metastatic colorectal cancer:Current and future perspectives

Colorectal cancer(CRC)is the fourth most commonly diagnosed cancer and the second leading cause of cancer death in both men and women in the United States,with about 142820 new cases and 50830 deaths expected in 2013.Metastatic disease(mCRC)remains a challenge for oncologists worldwide due to its potential comorbidities.Recently,chemotherapy regimens containing 5-fluorouracil,leucovorin,oxaliplatin and irinotecan combinations are a standard of care in the metastatic disease.Currently,biological therapies involving vascular endothelial growth factor and epidermal growth factor receptor pathways,such as bevacizumab and cetuximab,have emerged as good option for improving mCRC patient survival.Now,aflibercept plus standard chemotherapy has also been approved in second line regimen for mCRC patients.Our review will discuss novel biological drugs and their indications for mCRC patients and will bring future perspectives in this regard.     

艾迪注射液联合化疗治疗晚期结直肠癌疗效观察

结直肠癌是目前严重威胁人类健康的常见恶性肿瘤之一,晚期结直肠癌主要以全身化疗为主,为减轻化疗药物的毒副作用,提高患者生活质量,2006年3月-2008年12月笔者采用艾迪注射液联合FOL—FIRI方案治疗晚期结直肠癌患者31例,取得较好疗效,现报道如下。     

FOLFIRI plus bevacizumab as a second-line therapy for metastatic intrahepatic cholangiocarcinoma

AIM:To evaluate the efficacy and tolerance of FOLFIRI plus bevacizumab treatment outcome as second-line treatment for metastatic intrahepatic cholangiocarcinoma.METHODS:Thirteen consecutive patients with metastatic intrahepatic cholangiocarcinoma who were refractory tofirst-line therapy consisting of gemcitabine plus oxaliplatinbased first-line chemotherapy given intravenously via intra-arterial infusion were treated with FOLFIRI[irinotecan(180 mg/m2 i.v.over 90 min)concurrently with folinic acid(400 mg/m2 i.v.over 120 min)followed by fluorouracil(400 mg/m2 i.v.bolus)then fluorouracil 2400 mg/m2 intravenous infusion over 46 h]and bevacizumab(5mg/kg)every 2 wk.Tumor response was evaluated by computed tomography scan every 4 cycles.RESULTS:The best tumor responses using response evaluation criteria in solid tumor criteria were:complete response for 1 patient,partial response for 4 patients,and stable disease for 6 patients after 6 mo of follow-up.The response rate was 38.4%(95%CI:12.5-89)and the disease control rate was 84.5%(95%CI:42-100).Seven deaths occurred at the time of analysis,progression free survival was 8 mo(95%CI:7-16),and median overall survival was 20 mo(95%CI:8-48).No grade 4toxic events were observed.Four grade 3 hematological toxicities and one grade 3 digestive toxicity occurred.An adaptive reduction in chemotherapy dosage was required in 2 patients due to hematological toxicity,and a delay in chemotherapy cycles was required for 3 patients.CONCLUSION:FOLFIRI plus bevacizumab combination treatment showed promising efficacy and safety as second-line treatment for metastatic intrahepatic cholangiocarcinoma after failure of the first-line treatment of gemcitabine plus oxaliplatin chemotherapy.     

康莱特注射液联合FOLFIRI方案治疗晚期胃肠道肿瘤的临床观察

目的：探讨康莱特注射液联合FOLFIRI方案治疗晚期胃肠道肿瘤的疗效及毒副反应。方法：采用数字表法将94例晚期胃肠道肿瘤患者随机分成治疗组和对照组,治疗组采用康莱特注射液100ml,静滴,第1-7天,联合FOLFIRI方案治疗。对照组单用FOLFIRI方案化疗,2次为1个疗程,共6个疗程。观察临床有效率,毒副反应和生活质量。结果：治疗组和对照组化疗后临床有效率分别为34.1%和16.0%（P〈0.05）;治疗组和对照组生活质量提高分别为56.8%和12.0%（P〈0.05）;治疗组的骨髓抑制低于对照组（P〈0.05）,两组重度延迟性腹泻的发生率无显著差异（P〉0.05）。结论：康莱特注射液联合FOLFIRI方案治疗晚期胃肠道肿瘤能提高化疗疗效,改善患者的生活质量,降低骨髓抑制的发生率,起到减毒增效作用。     

A retrospective observational study on the safety and efficacy of first-line treatment with bevacizumab combined with FOLFIRI in metastatic colorectal cancer

Background:

Combination of bevacizumab and FOLFIRI has currently become one of the standard therapeutic regimens. However, published information is still limited. The objective of the present retrospective observational study is to analyse the response and toxicity of first-line treatment with FOLFIRI+bevacizumab in patients with metastatic colorectal cancer (mCRC).

Methods:

Data were collected from patients from nine Spanish sites diagnosed with mCRC, ECOG⩽2, whose first treatment for advanced disease was at least three cycles of FOLFIRI+bevacizumab.

Results:

A total of 95 patients were enrolled into the study: 64.2% males, median age of 59 years (53.2–67.1 years), ECOG=0–1 in 96.9% of patients. The main site of primary tumour was the colon (69.7%), and most metastases occurred in the liver (71.6%). Clinical benefit was detected in 67.4% (57.0–76.6; 95% confidence interval (CI)), with 8.4% of CR and 42.1% of PR. Median TTP was 10.6 months (10.0–11.3; 95% CI), PFS was 10.6 months (9.8–11.3; 95% CI), and OS was 20.7 months (17.1–24.2; 95% CI). Main grade I–II toxicities included haematological toxicity (35.8%), diarrhea (27.3%), mucositis (25.3%), asthenia (19.0%), haemorrhages (11.6%), and emesis (10.6%). Toxicities reaching grades III–IV were haematological toxicity (9.5%), diarrhea (8.5%), mucositis (5.3%), hepatic toxicity (2.1%), asthenia (2.1%), proteinuria (1.1%), emesis (1.1%), pain (1.1%), and colics (1.1%).

Conclusion:

Results of this study support the beneficial effect of adding bevacizumab to FOLFIRI regimen in terms of efficacy and show a favourable tolerability profile.