Pre-treatment lactate dehydrogenase levels as predictor of efficacy of first-line bevacizumab-based therapy in metastatic colorectal cancer patients

被引:97
作者
Scartozzi, M. [1 ]
Giampieri, R. [1 ]
Maccaroni, E. [2 ]
Del Prete, M. [2 ]
Faloppi, L. [2 ]
Bianconi, M. [2 ]
Galizia, E. [3 ]
Loretelli, C. [1 ]
Belvederesi, L. [1 ]
Bittoni, A. [2 ]
Cascinu, S. [1 ]
机构
[1] Univ Politecn Marche, AO Osped Riuniti, Clin Oncol Med, Ancona, Italy
[2] Univ Politecn Marche, Scuola Specializzaz Oncol Med, Ancona, Italy
[3] Osped Profili, Fabriano, Italy
关键词
bevacizumab; colorectal cancer; LDH; predictive factors; TUMOR ANGIOGENESIS; FACTOR PATHWAY; FLUOROURACIL; SERUM; LEUCOVORIN; EXPRESSION; OXALIPLATIN; IRINOTECAN; SURVIVAL; HYPOXIA;
D O I
10.1038/bjc.2012.17
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND: Lactate dehydrogenase (LDH) represents a predictive factor in colorectal cancer patients treated with the angiogenesis inhibitor PTK/ZK. We explored the role of pre-treatment LDH serum levels in colorectal cancer patients receiving first-line bevacizumab. METHODS: Metastatic colorectal cancer treated with first-line bevacizumab was eligible. A control group including all consecutive patients treated with chemotherapy alone was also considered. Pre-treatment LDH serum levels were collected for all cases. RESULTS: Median progression-free survival (PFS) in the control group for patients with high and low LDH levels was 4.2 and 8 months, respectively (P = 0.0003). Median overall survival (OS) was 19.6 and 34.9 months for patients with high and low LDH levels, respectively (P = 0.0014). In the bevacizumab group, partial responses were seen in 14 (58%) high-LDH and 8 (14%) low-LDH patients (P = 0.0243), respectively, median PFS was 7.3 and 8.5 months, respectively (P = 0.2), and median OS was 22 and 26.6 months, respectively (P = 0.7). CONCLUSION: High LDH levels correlated with worse prognosis. Bevacizumab seemed capable of improving clinical outcome in this specific group of patients who usually present with an adverse natural history. The improved response rate also suggests a role for LDH as a predictive marker. British Journal of Cancer (2012) 106, 799-804. doi:10.1038/bjc.2012.17 www.bjcancer.com Published online 7 February 2012 (C) 2012 Cancer Research UK
引用
收藏
页码:799 / 804
页数:6
相关论文
共 21 条
[1]   Serum lactate dehydrogenase levels and glycolysis significantly correlate with tumor VEGFA and VEGFR expression in metastatic CRC patients [J].
Azuma, Mizutomo ;
Shi, Michael ;
Danenberg, Kathleen D. ;
Gardner, Humphrey ;
Barrett, Carl ;
Jacques, Christian J. ;
Sherod, Andrew ;
Iqbal, Syma ;
El-Khoueiry, Anthony ;
Yang, Dongyun ;
Zhang, Wu ;
Danenberg, Peter V. ;
Lenz, Heinz-Josef .
PHARMACOGENOMICS, 2007, 8 (12) :1705-1713
[2]   Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer [J].
Brizel, DM ;
Schroeder, T ;
Scher, RL ;
Walenta, S ;
Clough, RW ;
Dewhirst, MW ;
Mueller-Klieser, W .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2001, 51 (02) :349-353
[3]   Association of Computed Tomography Morphologic Criteria With Pathologic Response and Survival in Patients Treated With Bevacizumab for Colorectal Liver Metastases [J].
Chun, Yun Shin ;
Vauthey, Jean-Nicolas ;
Boonsirikamchai, Piyaporn ;
Maru, Dipen M. ;
Kopetz, Scott ;
Palavecino, Martin ;
Curley, Steven A. ;
Abdalla, Eddie K. ;
Kaur, Harmeet ;
Charnsangavej, Chusilp ;
Loyer, Evelyne M. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2009, 302 (21) :2338-2344
[4]   Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer [J].
de Gramont, A ;
Figer, A ;
Seymour, M ;
Homerin, M ;
Hmissi, A ;
Cassidy, J ;
Boni, C ;
Cortes-Funes, H ;
Cervantes, A ;
Freyer, G ;
Papamichael, D ;
Le Bail, N ;
Louvet, C ;
Hendler, D ;
de Braud, F ;
Wilson, C ;
Morvan, F ;
Bonetti, A .
JOURNAL OF CLINICAL ONCOLOGY, 2000, 18 (16) :2938-2947
[5]   Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial [J].
Douillard, JY ;
Cunningham, D ;
Roth, AD ;
Navarro, M ;
James, RD ;
Karasek, P ;
Jandik, P ;
Iveson, T ;
Carmichael, J ;
Alakl, M ;
Gruia, G ;
Awad, L ;
Rougier, P .
LANCET, 2000, 355 (9209) :1041-1047
[6]  
FOLKMAN J, 1971, NEW ENGL J MED, V285, P1182
[7]   Hypoxia - A key regulatory factor in tumour growth [J].
Harris, AL .
NATURE REVIEWS CANCER, 2002, 2 (01) :38-47
[8]   Randomized, Placebo-Controlled, Phase III Study of First-Line Oxaliplatin-Based Chemotherapy Plus PTK787/ZK 222584, an Oral Vascular Endothelial Growth Factor Receptor Inhibitor, in Patients With Metastatic Colorectal Adenocarcinoma [J].
Hecht, J. Randolph ;
Trarbach, Tanja ;
Hainsworth, John D. ;
Major, Pierre ;
Jager, Elke ;
Wolff, Robert A. ;
Lloyd-Salvant, Katherine ;
Bodoky, Gyorgy ;
Pendergrass, Kelly ;
Berg, William ;
Chen, Bee-Lian ;
Jalava, Tarja ;
Meinhardt, Gerold ;
Laurent, Dirk ;
Lebwohl, David ;
Kerr, David .
JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (15) :1997-2003
[9]   Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer [J].
Hurwitz, H ;
Fehrenbacher, L ;
Novotny, W ;
Cartwright, T ;
Hainsworth, J ;
Heim, W ;
Berlin, J ;
Baron, A ;
Griffing, S ;
Holmgren, E ;
Ferrara, N ;
Fyfe, G ;
Rogers, B ;
Ross, R ;
Kabbinavar, F .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (23) :2335-2342
[10]   Phase III study of weekly high-dose infusional fluorouracil plus folinic acid with or without irinotecan in patients with metastatic colorectal cancer:: European Organisation for Research and Treatment of Cancer Gastrointestinal Group study 40986 [J].
Köhne, CH ;
van Cutsem, E ;
Wils, J ;
Bokemeyer, C ;
El-Serafi, M ;
Lutz, MP ;
Lorenz, M ;
Reichardt, P ;
Rückle-Lanz, H ;
Frickhofen, N ;
Fuchs, R ;
Mergenthaler, HG ;
Langenbuch, T ;
Vanhoefer, U ;
Rougier, P ;
Voigtmann, R ;
Müller, L ;
Genicot, B ;
Anak, Ö ;
Nordlinger, B .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (22) :4856-4865