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贝伐珠单抗联合 FOLFIRI-3 在生物治疗时代化疗耐药转移性结直肠癌患者中的应用。

Bevacizumab plus FOLFIRI-3 in chemotherapy-refractory patients with metastatic colorectal cancer in the era of biotherapies.

机构信息

Department of Medical Oncology, Georges Francois Leclerc Cancer Center, 1 rue du professeur Marion, Dijon 21000, France.

出版信息

Invest New Drugs. 2012 Apr;30(2):758-64. doi: 10.1007/s10637-010-9575-3. Epub 2010 Nov 6.

Abstract

BACKGROUND

The optimal chemotherapeutic regimen suitable for metastatic colorectal cancer (mCRC) patients previously treated with 5-fluorouracil (5FU), oxaliplatin, irinotecan and biotherapies remains an unresolved issue. The aim of this study was to evaluate the activity of bevacizumab combined with FOLFIRI-3 in mCRC after failure of prior chemotherapy including fluoropyrimidine, irinotecan and oxaliplatin.

METHODS

Patients were treated with bevacizumab in combination with FOLFIRI-3 every 14 days. The association between treatment efficacy and visceral fat area as measured by CT scan or Carcinoembryonic Antigen (CEA) change after 2 months was also studied.

RESULTS

Forty-nine consecutive patients were treated. Four hundred and twenty four cycles of chemotherapy were delivered. Median follow-up was 11 months. Eleven patients (22.4%) had an objective partial response and 26 (53.1%) were stabilized. Median progression-free survival (PFS) and overall survival (OS) were 7 and 13 months respectively. Four grade 4 adverse events occurred (1 digestive perforation, 1 rectal ulcer, 1 pulmonary embolism, and 1 febrile aplasia) but no toxic death was observed. Grade 3 adverse events occurred in 18 patients (38%) including asthenia in 15 patients (30%), nausea and vomiting in 4 patients (8%), diarrhea in 11 patients (22%), anemia in 4 patients (8%), neutropenia in 10 patients (20%) and thrombopenia in 4 patients (8%). Visceral Fat area was significantly lower in responder patients. CEA change at 2 months predicted improved overall survival.

CONCLUSION

This study suggests that bevacizumab combined with FOLFIRI3 may be active in mCRC patients after failure of all classical lines of chemotherapy.

摘要

背景

对于先前接受过氟尿嘧啶(5FU)、奥沙利铂、伊立替康和生物治疗的转移性结直肠癌(mCRC)患者,合适的化疗方案仍然是一个未解决的问题。本研究旨在评估贝伐珠单抗联合 FOLFIRI-3 在先前接受氟嘧啶、伊立替康和奥沙利铂化疗失败后的 mCRC 患者中的疗效。

方法

患者接受贝伐珠单抗联合 FOLFIRI-3 每 14 天治疗一次。还研究了 CT 扫描或 2 个月后癌胚抗原(CEA)变化测量的内脏脂肪面积与治疗效果之间的关联。

结果

连续治疗了 49 例患者。共给予 424 个周期的化疗。中位随访时间为 11 个月。11 例(22.4%)患者有客观部分缓解,26 例(53.1%)患者病情稳定。中位无进展生存期(PFS)和总生存期(OS)分别为 7 个月和 13 个月。发生 4 例 4 级不良事件(1 例消化道穿孔,1 例直肠溃疡,1 例肺栓塞,1 例发热性再生障碍性贫血),但无毒性死亡。18 例(38%)患者发生 3 级不良事件,包括 15 例(30%)乏力,4 例(8%)恶心呕吐,11 例(22%)腹泻,4 例(8%)贫血,10 例(20%)中性粒细胞减少症和 4 例(8%)血小板减少症。在有反应的患者中,内脏脂肪面积明显降低。2 个月时 CEA 的变化预测总生存期的改善。

结论

本研究表明,贝伐珠单抗联合 FOLFIRI3 可能对所有经典化疗方案失败后的 mCRC 患者有效。

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