Passardi Alessandro, Scarpi Emanuela, Tamberi Stefano, Cavanna Luigi, Tassinari Davide, Fontana Annalisa, Pini Sara, Bernardini Ilaria, Accettura Caterina, Ulivi Paola, Frassineti Giovanni Luca, Amadori Dino
Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
Unit of Biostatistics and Clinical Trials, IRST IRCCS, Meldola, Italy.
PLoS One. 2015 Aug 5;10(8):e0134732. doi: 10.1371/journal.pone.0134732. eCollection 2015.
To investigate the impact of pre-treatment lactate dehydrogenase (LDH) levels on the outcome of patients with metastatic colorectal cancer treated with first-line chemotherapy with or without the anti-VEGF monoclonal antibody, bevacizumab, in a phase III prospective multicentre randomized ITACa (Italian Trial in Advanced Colorectal Cancer) trial.
Three hundred and seventy patients enrolled onto the ITACa first-line trial were considered for this study, 176 receiving chemotherapy (either FOLFIRI or FOLFOX) plus bevacizumab and 194 receiving chemotherapy only. Pre-treatment LDH levels were evaluated to identify a potential correlation with progression-free survival (PFS), overall survival (OS) and objective response rate.
Information on pre-treatment LDH levels was available for 344 patients. High LDH levels were predictive of a lower median PFS (8.1 months vs. 9.2 months, p< 0.0001) and median OS (16.1 months vs. 25.2 months, p< 0.0001) in the overall population. In the chemotherapy plus bevacizumab group, median PFS was 9.1 and 9.8 months in patients with high LDH and low LDH, respectively (p= 0.073), whereas in the chemotherapy-only arm it was 6.9 and 9.1 months, respectively (p < 0.0001). In patients with high LDH, the addition of bevacizumab to chemotherapy led to a reduction in the rate of progressive disease (16.4 vs. 30.5%, p= 0.081) and to a prolonged PFS (p= 0.028).
A high LDH value was confirmed as a marker of poor prognosis. Bevacizumab reduced the progressive disease rate and improved PFS in the high-LDH subgroup, making serum LDH a potentially effective an easily available and marker to select patients who benefit from bevacizumab.
NCT01878422 ClinicalTrials.gov.
在一项III期前瞻性多中心随机ITACa(意大利晚期结直肠癌试验)试验中,研究治疗前乳酸脱氢酶(LDH)水平对接受一线化疗联合或不联合抗血管内皮生长因子单克隆抗体贝伐单抗治疗的转移性结直肠癌患者预后的影响。
本研究纳入了370名参加ITACa一线试验的患者,其中176名接受化疗(FOLFIRI或FOLFOX)联合贝伐单抗,194名仅接受化疗。评估治疗前LDH水平,以确定其与无进展生存期(PFS)、总生存期(OS)和客观缓解率之间的潜在相关性。
344名患者有治疗前LDH水平的信息。总体人群中,高LDH水平预示着较低的中位PFS(8.1个月对9.2个月,p<0.0001)和中位OS(16.1个月对25.2个月,p<0.0001)。在化疗联合贝伐单抗组中,高LDH和低LDH患者的中位PFS分别为9.1个月和9.8个月(p=0.073),而在单纯化疗组中分别为6.9个月和9.1个月(p<0.0001)。在高LDH患者中,化疗联合贝伐单抗可降低疾病进展率(16.4%对30.5%,p=0.081)并延长PFS(p=0.028)。
高LDH值被确认为预后不良的标志物。贝伐单抗降低了高LDH亚组的疾病进展率并改善了PFS,使血清LDH成为一种潜在有效的、易于获得的标志物,可用于选择能从贝伐单抗治疗中获益的患者。
NCT01878422 ClinicalTrials.gov。