Phase II study of bevacizumab and irinotecan as second-line therapy for patients with metastatic colorectal cancer previously treated with fluoropyrimidines, oxaliplatin, and bevacizumab
Phase II study of bevacizumab and irinotecan as second-line therapy for patients with metastatic colorectal cancer previously treated with fluoropyrimidines, oxaliplatin, and bevacizumab
复制标题
DOI：
10.1007/s00280-017-3255-3
复制
发表时间：
2017-03-01
影响因子：
3
通讯作者：
Hayashi, Kazuhiko
中科院分区：
文献类型：
--
作者：
Kuramochi, Hidekazu;Ando, Masayuki;Hayashi, Kazuhiko
氟尿嘧啶和亚叶酸联合伊立替康（FOLFIRI）加贝伐珠单抗（BV）广泛用作既往接受过氟尿嘧啶、奥沙利铂和BV治疗的转移性结直肠癌（mCRC）患者的二线化疗。FOLFIRI需要CV导管和输液泵，这对患者来说很不方便。没有足够的数据可用于表征首次疾病进展后氟尿嘧啶的有效性。在这项研究中，我们评估了伊立替康（CPT-11）联合BV作为二线治疗的有效性和安全性。既往接受过至少4个疗程的氟尿嘧啶、奥沙利铂和BV治疗的mCRC患者被指定接受CPT-11 150 mg/m2和BV 10 mg/kg每2周一次作为二线治疗。主要终点为无进展生存期（PFS），次要终点包括有效率（RR）、总生存期（OS）和不良事件。中位PFS为5.7个月（95% CI 4.2-7.3个月），RR为6.7%（范围0.8-22.1%）。3-4级不良事件包括白细胞减少（36.7%）、中性粒细胞减少（50%）、血小板减少（26.7%）、贫血（30%）、腹泻（3.3%）、厌食（6.7%）和高血压（3.3%）。CPT-11和BV的相对剂量强度分别为94.5%和96.3%。中位OS为11.8个月（未达到6.3个月），CPT-11联合BV治疗mCRC患者的疗效与既往FOLFIRI联合BV作为二线治疗的研究结果相当，毒性相对较低。CPT-11的剂量强度判定为耐受性。UMIN 000005228。
Fluorouracil and folinic acid with irinotecan (FOLFIRI) plus bevacizumab (BV) is widely used as second-line chemotherapy for patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidines, oxaliplatin, and BV. FOLFIRI requires a CV catheter and an infusion pump, which are inconvenient for patients. Sufficient data are not available for characterizing the effectiveness of fluoropyrimidines beyond first disease progression. In this study, we evaluated the efficacy and safety of irinotecan (CPT-11) plus BV as second-line therapy.Patients with mCRC previously treated with at least four courses of a fluoropyrimidine, oxaliplatin, and BV were designated to receive 150 mg/m(2) of CPT-11 and 10 mg/kg of BV every 2 weeks as second-line therapy. The primary endpoint was progression-free survival (PFS), and secondary endpoints included response rate (RR), overall survival (OS), and adverse events.Thirty patients from six institutes were enrolled from March 2011 to January 2014. The median PFS was 5.7 months (95% CI 4.2-7.3 months), and the RR was 6.7% (range 0.8-22.1%). Grades 3-4 adverse events included leucopenia (36.7%), neutropenia (50%), thrombocytopenia (26.7%), anemia (30%), diarrhea (3.3%), anorexia (6.7%), and hypertension (3.3%). Relative dose intensities were 94.5 and 96.3% for CPT-11 and BV, respectively. The median OS was 11.8 months (6.3 months-not reached).Administration of CPT-11 plus BV to patients with mCRC achieved comparable efficacies with relatively lower toxicities compared with the results of previous studies using FOLFIRI plus BV as second-line therapy. The dose intensity of CPT-11 was judged as satisfactory.UMIN000005228.