CA 19-9 tumour-marker response to chemotherapy in patients with advanced pancreatic cancer enrolled in a randomised controlled trial

被引:220
作者
Hess, Viviane [1 ]
Glimelius, Bengt [2 ]
Grawe, Philipp [1 ]
Dietrich, Daniel [3 ]
Bodoky, Gyoergy [4 ]
Ruhstaller, Thomas [5 ]
Bajetta, Emilio [6 ]
Saletti, Piercarlo [7 ]
Figer, Arie [8 ]
Scheithauer, Werner [9 ]
Herrmann, Richard [1 ,3 ]
机构
[1] Univ Basel Hosp, Dept Internal Med, Div Med Oncol, CH-4031 Basel, Switzerland
[2] Uppsala Univ, Dept Oncol Radiol & Clin Immunol, Uppsala, Sweden
[3] Swiss Grp Clin Canc Res Coordinating Ctr, Bern, Switzerland
[4] St Laszlo Hosp, Dept Oncol, Budapest, Hungary
[5] Kantonsspital St Gallen, Dept Internal Med, Div Oncol, St Gallen, Switzerland
[6] Natl Inst Study & Cure Tumours, Milan, Italy
[7] Oncol Inst So Switzerland, Bellinzona, Switzerland
[8] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel
[9] Univ Hosp Vienna, Dept Internal Med, Div Oncol, Vienna, Austria
关键词
INOPERABLE ADENOCARCINOMA; SURVIVAL; GEMCITABINE; CA19-9; RECOMMENDATIONS; SURROGATE; ANTIGEN; SERUM;
D O I
10.1016/S1470-2045(08)70001-9
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页码:132 / 138
页数:7
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