Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Clin Colorectal Cancer. 2012 Jun;11(2):101-11. doi: 10.1016/j.clcc.2011.05.006. Epub 2011 Nov 4.
Cetuximab (C), alone or with irinotecan, demonstrates activity in irinotecan-refractory colorectal cancer (CRC). Activity of 5-fluorouracil (5-FU), leucovorin (L), and bevacizumab (B), and preliminary data of cetuximab + bevacizumab, and toxicity profiles suggests that FOLF-CB (5-FU, L, C+B) may have activity with a favorable toxicity profile as first-line therapy.
Eligible patients were randomized at registration to either arm A (mFOLFOX6-B) (modified, 5-FU. L (folinic acid), oxaliplatin (O) + bevacizumab), administered days 1 and 15 of each 28-day cycle as bevacizumab 5 mg/kg, oxaliplatin 85 mg/m(2), leucovorin 400 mg/m(2), and 5-FU 400 mg/m(2) then 1200 mg/m(2)/day for 48 hours, or arm B (FOLF-CB), which included bevacizumab, leucovorin, and 5-FU as in arm A and cetuximab 400 mg/m(2) day 1 cycle 1; all other weekly cetuximab doses were 250 mg/m(2).
Two hundred forty-seven patients (arm A/arm B 124/123) were enrolled, and 239 were treated (118/121). Twelve-month progression-free survival (PFS) was 45%/32%, objective response rates (ORR) (complete response [CR] + partial response [PR]) were 52%/41%, disease control rates (CR+PR+stable disease [SD]) were 87%/83%, and median overall survival (OS) was 21/19.5 months, respectively. Grade 3-4 neutropenia was higher in arm A (28%/7%), as was grade 3 fatigue (12%/3%), and grade 3 neuropathy (11%/< 1%), whereas acneiform rash was confined to arm B. Retrospective analysis of KRAS mutational status did not demonstrate KRAS as a meaningful determinant of activity, except in arm B patients with KRAS-mutated tumors, which resulted in inferior PFS. Patient satisfaction favored the control (mFOLFOX6-B).
FOLF-CB was not superior to mFOLFOX6-B in terms of 12-month PFS and ORR, and was not more acceptable to patients. This trial supports the conclusion of other recently reported trials that concurrent cetuximab+bevacizumab should not be routinely used in metastatic CRC.
西妥昔单抗（C）单独或与伊立替康联合使用在伊立替康耐药的结直肠癌（CRC）中具有活性。氟尿嘧啶（5-FU）、亚叶酸（L）和贝伐珠单抗（B）的活性，以及西妥昔单抗联合贝伐珠单抗的初步数据和毒性特征表明，FOLF-CB（5-FU、L、C+B）作为一线治疗可能具有活性和良好的毒性特征。
符合条件的患者在登记时随机分为 A 组（mFOLFOX6-B）（改良，5-FU、L（亚叶酸）、奥沙利铂（O）+贝伐珠单抗），每 28 天周期的第 1 天和第 15 天给药，贝伐珠单抗 5mg/kg，奥沙利铂 85mg/m2，亚叶酸 400mg/m2，5-FU 400mg/m2，然后 48 小时内 1200mg/m2/天，或 B 组（FOLF-CB），包括贝伐珠单抗、亚叶酸和 A 组中的 5-FU，以及西妥昔单抗 400mg/m2 第 1 周期 1 天；所有其他每周西妥昔单抗剂量为 250mg/m2。
共纳入 247 例患者（A 组/ B 组 124/123），239 例患者接受治疗（118/121）。12 个月无进展生存期（PFS）分别为 45%/32%，客观缓解率（CR+PR）分别为 52%/41%，疾病控制率（CR+PR+SD）分别为 87%/83%，中位总生存期（OS）分别为 21/19.5 个月。A 组中性粒细胞减少症 3-4 级（28%/7%）、3 级疲劳（12%/3%）和 3 级神经病变（11%/<1%）较高，而痤疮样皮疹仅限于 B 组。KRAS 突变状态的回顾性分析并未表明 KRAS 是活性的有意义决定因素，除了 B 组 KRAS 突变肿瘤患者的 PFS 较差。患者对控制（mFOLFOX6-B）的满意度更高。
FOLF-CB 在 12 个月 PFS 和 ORR 方面并不优于 mFOLFOX6-B，也不如患者更能接受。该试验支持其他最近报告的试验的结论，即同时使用西妥昔单抗+贝伐珠单抗不应常规用于转移性 CRC。
