Saltz Leonard B, Lenz Heinz-Josef, Kindler Hedy L, Hochster Howard S, Wadler Scott, Hoff Paulo M, Kemeny Nancy E, Hollywood Ellen M, Gonen Mithat, Quinones Marcus, Morse Meroe, Chen Helen X
Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
J Clin Oncol. 2007 Oct 10;25(29):4557-61. doi: 10.1200/JCO.2007.12.0949. Epub 2007 Sep 17.
We evaluated the safety and efficacy of concurrent administration of two monoclonal antibodies, cetuximab and bevacizumab, in patients with metastatic colorectal cancer.
This was a randomized phase II study in patients with irinotecan-refractory colorectal cancer. All patients were naïve to both bevacizumab and cetuximab. Patients in arm A received irinotecan at the same dose and schedule as last received before study entry, plus cetuximab 400 mg/m2 loading dose, then weekly cetuximab 250 mg/m2, plus bevacizumab 5 mg/kg administered every other week. Patients in arm B received the same cetuximab and bevacizumab as those in arm A but without irinotecan.
Forty-three patients received cetuximab, bevacizumab, and irinotecan (CBI) and 40 patients received cetuximab and bevacizumab alone (CB). Toxicities were as would have been expected from the single agents. For the CBI arm, time to tumor progression (TTP) was 7.3 months and the response rate was 37%; for the CB arm, TTP was 4.9 months and the response rate was 20%. The overall survival for the CBI arm was 14.5 months and the overall survival for the CB-alone arm was 11.4 months.
Cetuximab and bevacizumab can be administered concurrently, with a toxicity pattern that seems to be similar to that which would be expected from the two agents alone. This combination plus irinotecan also seems to be feasible. The activity seen with the addition of bevacizumab to cetuximab, or to cetuximab plus irinotecan, seems to be favorable when compared with historical controls of cetuximab or cetuximab/irinotecan in patients who are naïve to bevacizumab.
我们评估了在转移性结直肠癌患者中同时给予两种单克隆抗体西妥昔单抗和贝伐单抗的安全性和有效性。
这是一项针对伊立替康难治性结直肠癌患者的随机II期研究。所有患者既往均未使用过贝伐单抗和西妥昔单抗。A组患者接受与研究入组前最后一次使用时相同剂量和给药方案的伊立替康，加用西妥昔单抗400mg/m²负荷剂量，然后每周给予西妥昔单抗250mg/m²，加用贝伐单抗5mg/kg，每2周给药一次。B组患者接受与A组相同的西妥昔单抗和贝伐单抗，但不使用伊立替康。
43例患者接受了西妥昔单抗、贝伐单抗和伊立替康（CBI）治疗，40例患者仅接受了西妥昔单抗和贝伐单抗（CB）治疗。毒性反应与单药治疗预期的情况相符。对于CBI组，肿瘤进展时间（TTP）为7.3个月，缓解率为37%；对于CB组，TTP为4.9个月，缓解率为20%。CBI组的总生存期为14.5个月，单纯CB组的总生存期为11.4个月。
西妥昔单抗和贝伐单抗可以同时给药，其毒性模式似乎与两种药物单独使用时预期的情况相似。这种联合方案加用伊立替康似乎也是可行的。与既往未使用过贝伐单抗的患者使用西妥昔单抗或西妥昔单抗/伊立替康的历史对照相比，在西妥昔单抗中加用贝伐单抗，或在西妥昔单抗加伊立替康中加用贝伐单抗所观察到的活性似乎较好。
