Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
Oncology. 2010;79(1-2):144-9. doi: 10.1159/000320686. Epub 2010 Dec 8.
To evaluate whether combination chemotherapy leads to early changes in plasma TIMP-1 and serum carcinoembryonic antigen (CEA) levels in patients with metastatic colorectal cancer (mCRC), and whether such changes relate to subsequent objective response, time to progression (TTP) and overall survival.
Eighty-eight patients with mCRC were included. Blood samples were collected before initiation and after 2, 4 and 6 weeks of treatment with an irinotecan-5-fluorouracil combination. Plasma TIMP-1 and serum CEA levels were determined by validated ELISA platforms. The first response evaluation was performed after 8 weeks of chemotherapy.
Median plasma TIMP-1 and serum CEA levels did not change significantly during 6 weeks of treatment. High plasma TIMP-1 and high serum CEA levels before treatment and at weeks 2, 4 and 6 were related to poor objective response. Moreover, high levels of plasma TIMP-1 before treatment and at weeks 2 and 4 were significantly associated with short TTP, while high levels of serum CEA at week 4 were significantly associated with short TTP. Finally, high levels of plasma TIMP-1 before and during treatment were significantly associated with poor overall survival; p < 0.0001 in all 4 determinations. A similar association between serum CEA and overall survival could only be demonstrated before treatment.
Median plasma TIMP-1 or serum CEA levels do not change significantly during the first 6 weeks of chemotherapy for mCRC. The results indicate that plasma TIMP-1 in particular and serum CEA may be valuable biomarkers even in samples collected during treatment with chemotherapy.
评估转移性结直肠癌（mCRC）患者联合化疗是否会导致血浆 TIMP-1 和血清癌胚抗原（CEA）水平的早期变化，以及这些变化是否与后续客观缓解、无进展生存期（TTP）和总生存期相关。
共纳入 88 例 mCRC 患者。在接受伊立替康-5-氟尿嘧啶联合化疗前及 2、4、6 周时采集血样。采用经验证的 ELISA 平台测定血浆 TIMP-1 和血清 CEA 水平。化疗 8 周后进行首次疗效评价。
6 周治疗期间，血浆 TIMP-1 和血清 CEA 水平中位数无明显变化。治疗前及治疗后 2、4、6 周时高血浆 TIMP-1 和高血清 CEA 水平与客观缓解不良相关。此外，治疗前和治疗后 2、4 周时高血浆 TIMP-1 水平与 TTP 较短显著相关，而治疗后 4 周时高血清 CEA 水平与 TTP 较短显著相关。最后，治疗前和治疗过程中高血浆 TIMP-1 水平与较差的总生存期显著相关；在所有 4 次测定中，p<0.0001。仅在治疗前，血清 CEA 与总生存期之间存在类似的关联。
在 mCRC 患者接受化疗的前 6 周内，血浆 TIMP-1 或血清 CEA 水平无明显变化。结果表明，特别是血浆 TIMP-1 和血清 CEA 可能是有价值的生物标志物，即使在化疗期间采集的样本中也是如此。
