在转移性结直肠腺癌患者的 II 期试验中 COX-2 表达与 COX-2 抑制剂疗效的相关性。
Association between COX-2 expression and effectiveness of COX-2 inhibitors in a phase II trial in patients with metastatic colorectal adenocarcinoma.
机构信息
Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center& Research Institute, Tampa, FL, USA.
出版信息
Anticancer Res. 2012 Aug;32(8):3559-63.
AIM
The role for the cyclooxygenase-2 (COX-2) pathway in colorectal carcinogenesis has been suggested in pre-clinical models. In a previously reported phase II trial, the addition of COX-2 inhibitor celecoxib to irinotecan and capecitabine did not appear to significantly increase the activity of chemotherapy in patients with metastatic colorectal carcinoma (mCRC). We evaluated the COX-2 expression in the available tumors from enrolled patients by immunohistochemistry, as well as its correlation with clinical outcome.
PATIENTS AND METHODS
Fifty-one patients with mCRC were enrolled in the phase II study between June 2002 and November 2005. Patients received a combination of irinotecan 70 mg/m(2) over 30 min i.v. on days 1 and 8, capecitabine 1,000 mg/m(2) twice per day orally on days 1-14 and the COX-2 inhibitor celecoxib at a daily dose of 800 mg continuously. Cycles were repeated every 21 days. Formalin-fixed paraffin-embedded tumor tissue samples were available for 17 patients enrolled on this study. COX-2 expression was evaluated by immunohistochemistry and was correlated with clinical outcome.
RESULTS
In the phase II study, the objective response rate was 41%. The median time to progression was 7.7 months and median survival time was 21.2 months. Tumor COX-2 expression, by immunohistochemistry, was assessed for 17 patients enrolled in the same phase II study. While not statistically significant, the response rate was better for patients in the low COX-2 expression group, while time to progression and overall survival was longer in patients in the high COX-2 expression group. This discrepancy can be partially attributed to the small sample size.
CONCLUSION
In the previously published phase II study, the addition of celecoxib to irinotecan and capecitabine did not appear to significantly increase the activity of chemotherapy. COX-2 expression by immunohistochemistry was neither prognostic nor predictive for response.
目的
环氧化酶-2（COX-2）途径在结直肠癌发生中的作用在临床前模型中已得到证实。在之前报道的一项 II 期试验中，向接受伊立替康和卡培他滨治疗的转移性结直肠癌（mCRC）患者中添加 COX-2 抑制剂塞来昔布似乎并没有显著增加化疗的活性。我们通过免疫组织化学评估了入组患者中可获得的肿瘤中的 COX-2 表达，并评估了其与临床结果的相关性。
患者和方法
2002 年 6 月至 2005 年 11 月期间，51 例 mCRC 患者入组该 II 期研究。患者接受伊立替康 70mg/m²静脉输注 30min，第 1 和 8 天；卡培他滨 1000mg/m²每日 2 次口服，第 1-14 天；COX-2 抑制剂塞来昔布每日 800mg 持续服用。每 21 天重复一个周期。本研究入组的 17 例患者有福尔马林固定石蜡包埋肿瘤组织样本。通过免疫组织化学评估 COX-2 表达，并与临床结果相关联。
结果
在 II 期研究中，客观缓解率为 41%。无进展生存期为 7.7 个月，总生存期为 21.2 个月。对同一项 II 期研究中入组的 17 例患者的肿瘤 COX-2 表达进行了免疫组织化学评估。虽然没有统计学意义，但低 COX-2 表达组的缓解率更好，而高 COX-2 表达组的疾病进展时间和总生存期更长。这种差异部分归因于样本量小。
结论
在之前报道的 II 期研究中，向伊立替康和卡培他滨中添加塞来昔布似乎并没有显著增加化疗的活性。免疫组织化学 COX-2 表达既不能预测预后，也不能预测对治疗的反应。
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