CA 19-9 tumour-marker response to chemotherapy in patients with advanced pancreatic cancer enrolled in a randomised controlled trial
CA 19-9 tumour-marker response to chemotherapy in patients with advanced pancreatic cancer enrolled in a randomised controlled trial
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DOI：
10.1016/s1470-2045(08)70001-9
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发表时间：
2008-02-01
期刊：
影响因子：
51.1
通讯作者：
Herrmann, Richard
中科院分区：
文献类型：
--
作者：
Hess, Viviane;Glimelius, Bengt;Herrmann, Richard
背景对接受化疗的晚期胰腺癌患者进行的几项研究表明，肿瘤标志物碳水化合物抗原（CA）19-9浓度的降低与生存期的延长有关。本研究的目的是检验以下假设：基线血清CA 19-9浓度的早期降低（在第42天，两个化疗周期后）至少50%与生存期延长相关，并且CA 19-9浓度从基线浓度降低至少50%至治疗期间任何时间测量的最低值（最低值）是预后的意义，使其作为一个替代endpoint为survival.Methods CA 19-9血清浓度测定基线和此后每3周在组织学证实的晚期胰腺癌患者登记在吉西他滨与吉西他滨加卡培他滨的随机试验。如果基线血清CA 19-9浓度低于实验室正常上限（ULN）或如果该测量值缺失，则排除患者。有和没有CA 19-9反应的患者之间的生存率比较通过界标方法校正了时间偏倚。本研究所基于的试验在美国国家癌症研究所网站http：//www.example.com的临床试验网站上注册www.clinicaltrials.gov/ct/show/NCT00030732.Findings319名随机化患者中的247名可评估基线血清CA 19-9浓度的分析，并且其中175名患者可评估肿瘤标志物对治疗的反应。基线CA 19-9浓度等于或高于中位值（即59 × ULN）的患者的中位总生存期为5.8个月（95% CI 5.1-7.0），显著短于基线浓度低于中位值的患者（10.3个月[95% CI 8.6-12.8]，p < 0.0001）。两个周期化疗后CA 19-9浓度早期降低至少50%与较长的总生存期无关，与未降低至少50%的患者相比，（中位10.1个月[9.2-12.7] vs 8.6个月[6.9-11.21，p=0.53;死亡风险比1.11[0.81-1.52]）。此外，在CA 19 - 9浓度最低值时，CA 19 -9浓度降低至少50%与与与那些没有降低至少50%的患者相比更长的总生存期无关（中位数7.8个月[6.5-10.11 vs 6.7个月[5.5-9.8]，p=0.74; 0.95[0.69-1.31]）。解释治疗前血清CA 19-9浓度是生存的独立预后因素，但化疗期间血药浓度的降低与生存期的延长没有显著相关性。我们的数据表明，化疗期间CA 19-9应答不是临床试验中生存率的有效替代终点。
Background Several studies in patients undergoing chemotherapy for advanced pancreatic carcinoma have linked a decrease in the concentration of the tumour marker carbohydrate antigen (CA) 19-9 to lengthened survival. The aim of this study was to test the hypotheses that an early decrease in baseline serum CA 19-9 concentration (on day 42, after two cycles of chemotherapy) by at least 50% is associated with lengthened survival, and that a decrease in CA 19-9 concentration of at least 50% from the baseline concentration to the lowest value measured at any time during treatment (nadir) is of prognostic significance, enabling its use as a surrogate endpoint for survival.Methods CA 19-9 serum concentration was measured at baseline and every 3 weeks thereafter in patients with histologically proven advanced pancreatic carcinoma enrolled in a randomised trial of gemcitabine versus gemcitabine plus capecitabine. Patients were excluded if baseline serum CA 19-9 concentration was below the upper limit of normal (ULN) in the laboratory or if this measurement was missing. Comparisons of survival between patients with and without a CA 19-9 response were corrected for the guarantee-time bias by the landmark method. The trial on which this study is based is registered on the clinical trials site of the US National Cancer Institute website http:// www.clinicaltrials.gov/ct/show/NCT00030732.Findings 247 of 319 randomised patients were assessable for analysis of baseline serum CA 19-9 concentration, and, of these, 175 patients were assessable for tumour-marker response to treatment. Median overall survival for patients with a baseline CA 19-9 concentration equal to or above the median value (ie, 59xULN) was 5.8 months (95% Cl 5.1-7.0), which was significantly shorter than that for patients with baseline concentrations below the median value (10.3 months [95% Cl 8.6-12.8], p < 0.0001). An early decrease in CA 19-9 concentration of at least 50% after two cycles of chemotherapy was not associated with a longer overall survival compared with patients who did not have a decrease of at least 50% (median 10.1 months [9.2-12.7] vs 8.6 months [6.9-11.21, p=0.53; hazard ratio for death 1.11[0.81-1.52]). Furthermore, a decrease in CA 19-9 concentration of at least 50% reached at the CA 19-9 nadir concentration was not associated with a longer overall survival compared with those patients who did not have a decrease of at least 50% (median 7.8 months [6.5-10.11 vs 6.7 months [5.5-9.8], p=0.74; 0.95[0.69-1.31]) after adjusting for the guarantee-time bias.Interpretation Pretreatment serum CA 19-9 concentration is an independent prognostic factor for survival, but a decrease in concentration during chemotherapy is not significantly associated with lengthened survival compared with those who did not have a corresponding decrease. Our data suggest that CA 19-9 response during chemotherapy is not a valid surrogate endpoint for survival in clinical trials.