Role of cetuximab and sorafenib in treatment of metastatic colorectal cancer

被引:21
作者
Galal, K. M. [1 ,2 ]
Khaled, Z. [2 ,3 ]
Mourad, Abdel Monem M. [2 ,4 ]
机构
[1] Cairo Univ, Radiotherapy & Oncol Ctr NEMROCK, Cairo, Egypt
[2] Saudi German Hosp, Ctr Oncol, Riyadh, Saudi Arabia
[3] Tanta Univ, Dept Internal Med, Tanta, Egypt
[4] Assiut Univ, Dept Radiol, Assiut, Egypt
关键词
K-ras; cetuximab; sorafenib; metastatic colorectal carcinoma; K-RAS MUTATIONS; PHASE-II; KINASE; EGFR; PANITUMUMAB; EXPRESSION; KRAS; DISTRIBUTIONS; IRINOTECAN; INHIBITOR;
D O I
10.4103/0019-509X.75825
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND: The relationship of epidermal growth factor receptors (EGFR) pathway, such as PI3K, K-ras, and B-raf, with response to EGFR-targeted antibodies is less well studied. AIM: To assess sorafenib with cetuximab in treating metastatic colorectal cancer. SETTINGS AND DESIGN: Thirty-five patients with metastatic colorectal cancer were randomized to receive cetuximab with or without oral sorafenib. PATIENTS AND METHODS: Patients received cetuximab IV weekly for four weeks and oral sorafenib twice daily on days 1 - 28, with recycling every four weeks. The primary end point was the response rate (partial and complete), while the secondary end points were the adverse effects, time to progression and overall survival. STATISTICAL ANALYSIS was made using the Statistical Product and Service Solutions, using SPSS 10.0, with estimation of both time to progression and overall survival time by the Kaplan-Meier method and comparing the two groups with the use of a log-rank test. RESULTS: Partial response was higher in cetuximab-sorafenib (EN), which constituted 33.3% compared to 17.6% in the cetuximab group (P = 0.44). Progression-free survival had a statistically higher significant difference in wild K-ras compared to mutant K-ras cases (P = .0001). Median overall survival was seven and five months in the (EN) and (E) groups respectively (P = 0.49). CONCLUSION: K-ras and B-raf was a predictor of response, so genotyping of tumors was needed for defining the patient population that was likely to benefit from the targeted therapy. A combination of therapy that simultaneously targets K-ras and B-raf could be a useful approach to increase the number of patients who may benefit from anti-EGFR therapy.
引用
收藏
页码:47 / 54
页数:8
相关论文
共 50 条
[41]   Mutational analysis of primary and metastatic colorectal cancer samples underlying the resistance to cetuximab-based therapy [J].
Nemecek, Radim ;
Berkovcova, Jitka ;
Radova, Lenka ;
Kazda, Tomas ;
Mlcochova, Jitka ;
Vychytilova-Faltejskova, Petra ;
Slaby, Ondrej ;
Svoboda, Marek .
ONCOTARGETS AND THERAPY, 2016, 9 :4695-4703
[43]   Standard chemotherapy with cetuximab for treatment of colorectal cancer [J].
Li, Xin-Xiang ;
Liang, Lei ;
Huang, Li-Yong ;
Cai, San-Jun .
WORLD JOURNAL OF GASTROENTEROLOGY, 2015, 21 (22) :7022-7035
[44]   KRAS mutation testing in the treatment of metastatic colorectal cancer with anti-EGFR therapies [J].
Soulieres, D. ;
Greer, W. ;
Magliocco, Anthony M. ;
Huntsman, D. ;
Young, S. ;
Tsao, M-S. ;
Kamel-Reid, S. .
CURRENT ONCOLOGY, 2010, 17 :S31-S40
[45]   The Role of HER-3 Expression in the Prediction of Clinical Outcome for Advanced Colorectal Cancer Patients Receiving Irinotecan and Cetuximab [J].
Scartozzi, Mario ;
Mandolesi, Alessandra ;
Giampieri, Riccardo ;
Bittoni, Alessandro ;
Pierantoni, Chiara ;
Zaniboni, Alberto ;
Galizia, Eva ;
Giustini, Lucio ;
Silva, Rosa Rita ;
Bisonni, Renato ;
Berardi, Rossana ;
Biscotti, Tommasina ;
Biagetti, Simona ;
Bearzi, Italo ;
Cascinu, Stefano .
ONCOLOGIST, 2011, 16 (01) :53-60
[46]   Standard chemotherapy with cetuximab for treatment of colorectal cancer [J].
Xin-Xiang Li ;
Lei Liang ;
Li-Yong Huang ;
San-Jun Cai .
World Journal of Gastroenterology, 2015, (22) :7022-7035
[47]   First-line targeted therapies in the treatment of metastatic colorectal cancer - role of cetuximab [J].
Tonini, Giuseppe ;
Calvieri, Alice ;
Vincenzi, Bruno ;
Santini, Daniele .
ONCOTARGETS AND THERAPY, 2009, 2 :73-82
[48]   Fluorouracil, Leucovorin, and Oxaliplatin With and Without Cetuximab in the First-Line Treatment of Metastatic Colorectal Cancer [J].
Bokemeyer, Carsten ;
Bondarenko, Igor ;
Makhson, Anatoly ;
Hartmann, Joerg T. ;
Aparicio, Jorge ;
de Braud, Filippo ;
Donea, Serban ;
Ludwig, Heinz ;
Schuch, Gunter ;
Stroh, Christopher ;
Loos, Anja H. ;
Zubel, Angela ;
Koralewski, Piotr .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (05) :663-671
[49]   Genetic and immune factors underlying the efficacy of cetuximab and panitumumab in the treatment of patients with metastatic colorectal cancer [J].
Krawczyk, Pawel Adam ;
Kowalski, Dariusz M. .
WSPOLCZESNA ONKOLOGIA-CONTEMPORARY ONCOLOGY, 2014, 18 (01) :7-16
[50]   RAS testing and cetuximab treatment for metastatic colorectal cancer: a cost-effectiveness analysis in a setting with limited health resources [J].
Wu, Bin ;
Yao, Yuan ;
Zhang, Ke ;
Ma, Xuezhen .
ONCOTARGET, 2017, 8 (41) :71164-71172