Giampieri Riccardo, Puzzoni Marco, Daniele Bruno, Ferrari Daris, Lonardi Sara, Zaniboni Alberto, Cavanna Luigi, Rosati Gerardo, Pella Nicoletta, Zampino Maria Giulia, Sozzi Pietro, Germano Domenico, Zagonel Vittorina, Codecà Carla, Libertini Michela, Labianca Roberto, Cascinu Stefano, Scartozzi Mario
Department of Medical Oncology Unit, University Hospital and Università Politecnica delle Marche, Ancona, Italy.
Department of Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy.
Br J Cancer. 2017 Oct 10;117(8):1099-1104. doi: 10.1038/bjc.2017.234. Epub 2017 Sep 19.
Previous findings suggested that bevacizumab might be able to improve response rate (RR) in colorectal cancer patients with high lactic dehydrogenase (LDH) basal levels.
We conducted a phase II trial to prospectively ascertain whether bevacizumab in combination with FOLFIRI could have an improved clinical activity in patients with high LDH serum levels. Primary end point of the study was RR; secondary end points were median overall survival and median progression-free survival (mPFS).
A total of 81 patients were enrolled. No difference in terms of ORR (39% vs 31% for low vs high LDH level stratum, P=0.78) and mPFS (14.16 vs 10.29 months, HR: 1.07, 95% CI: 0.51-2.24, P=0.83) between the strata was observed, whereas overall survival (OS) was significantly longer for patients with low LDH (24.85 vs 15.14 months, HR: 4.08, 95% CI: 1.14-14.61, P=0.0004). In a not-pre-planned exploratory analysis using different cut-off ranges for LDH, we observed RR up to 70%, with no improvement in progression-free survival or OS.
The CENTRAL trial failed to demonstrate that high LDH levels were related to a significantly improved RR in patients receiving first-line FOLFIRI and bevacizumab. The LDH serum levels should then no further be investigated as a predictive factor in this setting.
既往研究结果提示，贝伐单抗可能能够提高乳酸脱氢酶（LDH）基础水平较高的结直肠癌患者的缓解率（RR）。
我们开展了一项II期试验，以前瞻性地确定贝伐单抗联合FOLFIRI方案对LDH血清水平较高的患者是否具有更好的临床活性。该研究的主要终点为RR；次要终点为中位总生存期和中位无进展生存期（mPFS）。
共纳入81例患者。两组间客观缓解率（ORR）（低LDH水平组 vs 高LDH水平组分别为39% vs 31%，P = 0.78）和mPFS（14.16个月 vs 10.29个月，风险比：1.07，95%置信区间：0.51 - 2.24，P = 0.83）无差异，而低LDH患者的总生存期（OS）显著更长（24.85个月 vs 15.14个月，风险比：4.08，95%置信区间：1.14 - 14.61，P = 0.0004）。在一项未预先计划的探索性分析中，我们使用不同的LDH临界值范围，观察到RR高达70%，但无进展生存期或总生存期的改善。
CENTRAL试验未能证明高LDH水平与接受一线FOLFIRI和贝伐单抗治疗的患者RR显著改善相关。因此，在这种情况下，不应再将LDH血清水平作为预测因素进行进一步研究。
