Clinical outcome of dogs diagnosed with canine inflammatory mammary cancer treated with metronomic cyclophosphamide, a COX ‐2 inhibitor and toceranib phosphate

Author(s):  
D. Alonso‐Miguel ◽  
G. Valdivia ◽  
P. García‐San José ◽  
A. Alonso‐Diez ◽  
I. Clares ◽  
...  
2013 ◽  
Vol 197 (2) ◽  
pp. 427-432 ◽  
Author(s):  
Mónica Clemente ◽  
Ana Rodríguez Sánchez-Archidona ◽  
David Sardón ◽  
Lucía Díez ◽  
Asunción Martín-Ruiz ◽  
...  
Keyword(s):  

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10010-10010
Author(s):  
D. Yang ◽  
D. Vallböhmer ◽  
W. Zhang ◽  
S. Iqbal ◽  
A. El-Khoueiry ◽  
...  

10010 Background: 5-flurouracil (5-FU) and Oxaliplatin-based therapy is one of the most frequently used combinations in the treatment of advanced colorectal cancer (CRC). There are no validated and established predictive factors for clinical outcome following 5-FU/Oxaliplatin treatment. We had shown an association between intratumoral mRNA levels of TS and ERCC1 involved in 5-FU metabolism and DNA repair, respectively, and survival to 5-FU/Oxaliplatin chemotherapy in advanced CRC in a retrospective study. Now we investigated whether intratumoral mRNA levels of these two genes and others involved in 5-FU metabolism (DPD, TP, dUTPase), DNA repair (ERCC2, XRCC1), angiogenesis (COX-2, EGFR, IL-8, PLA2), and drug detoxification (GSTP-1) predict the clinical outcome of patients with CRC in a prospectively designed biomarker study. Methods: 85 patients with metastatic CRC treated with second-line 5-FU/Oxaliplatin from the prospective trial were included. mRNA levels of 12 genes were assessed from paraffin- embedded tissue samples using laser capture microdissection and quantitative Real-time PCR. Overall survival (OS) was the primary endpoint. Progression-free survival (PFS), response, and toxicity were the secondary endpoints. Results: There were 40 women and 45 men (median age 60 years; range 29–87), median survival of 9.7 ms, median PFS of 4.2 ms, CR in 1 (1%) patient, PR in 15 (18%), SD in 36 (43%) and PD in 32 (38%) patients. High intratumoral mRNA levels of PLA2, TP, GSPTP-1 and low mRNA levels of COX-2 were each significantly associated with shorter OS (P≤0.05, log-rank test). There was a trend in the association between high mRNA levels of PLA2 and shorter PFS (P=0.08). In addition, high mRNA levels of XRCC1 and IL-8 were each significantly associated with high risk of cumulative grade 3+ toxicity (P≤0.05). No significant association was found between mRNA levels and response to 5-FU/Oxaliplatin. Conclusions: This study suggests that mRNA levels of PLA2, TP, GSTP-1, COX-2, XRCC1, and IL-8 may be useful to predict the outcome of patients with metastatic CRC with second-line 5-FU/Oxaliplatin chemotherapy. These findings should be validated with future basic sciences studies and prospective clinical trials. [Table: see text]


2011 ◽  
Vol 189 (1) ◽  
pp. 77-82 ◽  
Author(s):  
Felisbina L. Queiroga ◽  
Isabel Pires ◽  
Margarida Parente ◽  
Hugo Gregório ◽  
Carlos S. Lopes

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3606-3606
Author(s):  
D. Vallbohmer ◽  
H. Kuramochi ◽  
D. Shimizu ◽  
K. D. Danenberg ◽  
J. N. Nielsen ◽  
...  

3606 Background: Capecitabine offers physicians a more convenient treatment for advanced colorectal cancer (CRC), with manageable toxicity and antitumor activity comparable to that of continuous-infusion therapies with 5-fluorouracil (5-FU). However, there are no validated and established predictive factors for clinical outcome of capecitabine efficacy in CRC. Therefore we investigated whether intratumoral mRNA expression levels of genes involved in the capecitabine/5-FU metabolism (cytidine deaminase (CDA), dihydropyrimidine dehydrogenase (DPD), folylpolyglutamate synthase (FPGS), gamma-glutamyl hydrolase (GGH), thymidine phosphorylase (TP), thymidylate synthase (TS)) and in angiogenesis (cyclooxygenase 2 (Cox-2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF)) are associated with the clinical outcome of patients with metastatic CRC treated with first-line capecitabine. Methods: Thirty-seven patients with metastatic CRC were enrolled in this study and treated with single agent capecitabine.The intratumoral mRNA levels of CDA, COX-2, DPD, EGFR, FPGS; GGH, TP, TS, and VEGF were assessed from paraffin-embedded tissue samples using laser-capture-microdissection methods and quantitative real-time PCR. Results: There were20 women and 17 men with a median age of 61 years (range 49–74). The median progression-free survival was 6.7 months (95% CI, 4.8–11.6 months), with a median follow up of 14.4 months (range: 1.3 to 18.7 months). Complete response was observed in 1 (3%), partial response in 6 (20%), stable disease in 14 (47%) and progressive disease in 9 (30%) patients (response was inevaluable in 7 patients). Higher gene expression levels of DPD were associated with resistance to capecitabine (P= 0.032; Kruskal-Wallis test). Patients with a lower mRNA amount of DPD (≤0.46) had a longer progression-free survival compared with patients that had a higher mRNA amount (8.0 vs. 3.3 months; adjusted P=0.048; log-rank test). Conclusions: This pilot study suggests that intratumoral gene expression levels of DPD may be useful to predict the clinical outcome of patients with metastatic CRC with first-line single agent capecitabine treatment. Our data are hypothesis generating and should be validated in larger and prospective clinical trials. [Table: see text]


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4129-4129 ◽  
Author(s):  
F. Nagashima ◽  
W. Zhang ◽  
M. Gordon ◽  
H. M. Chang ◽  
G. Lurje ◽  
...  

4129 Background: A phase II study of cetuximab (IMCL-0144) has shown response rate of 12 % in patients with EGFR expressing metastatic colorectal cancer (mCRC). Recently, we reported that polymorphisms in the EGFR pathway may be useful molecular markers to predict clinical outcome. In this larger study, we tested whether polymorphisms in genes involved in the EGFR and angiogenesis pathway will be associated with clinical outcome. Methods: We analyzed 136 tissue samples from 346 mCRC pts enrolled in the phase II study of cetuximab (IMCL-0144), 133 cases were informative. The response rate in these 133 pts was 10% with a median progression-free survival (PFS) of 1.3 months (95% CI, 1.2 to 1.5) and an overall survival time (OS) of 5.5 months (95% CI, 4.1 to 7.5). Gr3–4 toxicity was observed in 56%. Gene polymorphisms of EGFR, Cox-2, EGF, cyclin D1, fragment c γ receptor 2A (FCGR2A), FCGR3A, VEGF, IL-8 were assessed from gDNA extracted from tissue samples by using PCR-based RFLP technique. Univariate analysis (Fisher’s exact test for response; log-rank test for PFS and OS) was performed to examine associations between polymorphisms and clinical outcome. A classification and regression tree (CART) analysis was used to identify subgroups of patients who were more likely to benefit from cetuximab. Results: Pts with EGFR G497C GA, Cox-2 G-765C CC, EGF A61G GG genotype showed better PFS (p=0.02, 1.8mo. vs. 1.2mo.; p=0.03, 6.9mo. vs. 1.3mo.; p=0.04, 1.4mo. vs. 1.2mo.), respectively. We found trends in associations between Cox-2 and tumor response (p=0.09), between EGF and Gr3–4 toxixity (p=0.06). CART analyses indicated that germline polymorphisms in EGFR, EGF, Cox-2, Cyclin D1, IL-8, FCGR2A and FCGR3A genes could be used to identify patients who benefit most likely of cetuximab therapy. Conclusions: Our data suggest that the polymorphisms of EGFR, Cox-2, and EGF may be useful molecular markers to predict clinical outcome in mCRC pts treated with single-agent cetuximab. And prospective studies will need to be done to confirm these preliminary findings. [Table: see text]


Oncotarget ◽  
2020 ◽  
Vol 11 (32) ◽  
pp. 3048-3060
Author(s):  
Leandro E. Mainetti ◽  
María José Rico ◽  
Cintia Daniela Kaufman ◽  
Monica Carolina Grillo ◽  
Julian Guercetti ◽  
...  

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 5055-5055
Author(s):  
K. Rodabaugh ◽  
Y. Wu ◽  
D. Driscoll ◽  
K. Odunsi ◽  
S. Lele ◽  
...  

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