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Anti-epidermal Growth Factor Receptor (anti-epidermal + growth_factor_receptor)
Selected AbstractsAdditional value of EGFR downstream signaling phosphoprotein expression to KRAS status for response to anti-EGFR antibodies in colorectal cancer,INTERNATIONAL JOURNAL OF CANCER, Issue 6 2010Geraldine Perkins Abstract KRAS mutations are a strong predictive marker of resistance to anti-epidermal growth factor receptor (EGFR) antibodies in advanced colorectal cancer (CRC) but only a subset of wild-type (WT) KRAS patients are responders, suggesting the existence of additional markers of resistance to this treatment. The activation of EGFR downstream signaling pathways may be one of these ones. In a series of 42 patients with advanced CRC treated with cetuximab/panitumumab, for whom KRAS status was previously determined, we retrospectively analyzed the intratumor expression of EGFR downstream signaling phosphoproteins of the RAS/MAPK and PI3K/AKT pathways (pERK1/2, pMEK1, pAKT, pP70S6K and pGSK3,) using Bio-Plex® phosphoprotein array. Association with tumor response, progression-free survival (PFS) and overall survival (OS) was assessed. The expression of all the phosphoproteins was higher in KRAS mutated tumors than in WT tumors. The expression of pP70S6K was lower in responders than in nonresponder patients. In univariate analysis, patients with high pMEK1 or pP70S6K expression had a shorter PFS than those with low expression. Patients with high pP70S6K expression also had a shorter OS. In multivariate analysis, PFS was shorter for patients with high pMEK1 or pP70S6K expression, independently of KRAS status, as OS for patients with high pP70S6K expression. Therefore, WT KRAS patients with high pP70S6K expression had a shorter survival than those with low expression. Our results suggest the importance of EGFR downstream signaling phosphoproteins expression in addition to KRAS status to define the subgroup of patients who will not benefit from anti-EGFR therapy. [source] A recombinant humanized anti-insulin-like growth factor receptor type I antibody (h7C10) enhances the antitumor activity of vinorelbine and anti-epidermal growth factor receptor therapy against human cancer xenograftsINTERNATIONAL JOURNAL OF CANCER, Issue 2 2005Liliane Goetsch Abstract Interaction of insulin-like growth factor receptor I (IGF-IR) with its ligands has been reported to induce cell proliferation, transformation and blockade of cell apoptotic functions. IGF-IR is overexpressed on numerous tumor cell types and its blockade could be of importance for anti-cancer therapy. We have generated a humanized anti-IGF-IR antibody h7C10 that blocks in vitro IGF-I and IGF-II-induced cell proliferation of MCF-7 breast cancer cells. Analysis of the IGF-I transduction cascade demonstrated that the humanized anti-IGF-IR antibody and its murine parental form block IGF-I-induced tyrosine phosphorylation, both its ,-chain and IRS-1 tyrosine phosphorylation. This presumably leads to cell cycle arrest and, consequently, growth inhibition. Treatment of nude mice bearing either human breast cancer cells (MCF-7) or non small lung cancer cells (A549) with h7C10, or its murine parental form 7C10, inhibited significantly tumor growth. An almost complete inhibition of A549 tumor growth was observed when mice were treated with the anti-IGF-IR antibody combined with either a chemotherapeutic agent, Vinorelbine or an anti-epidermal growth factor receptor (EGFR) antibody, 225. Combined therapy prolonged significantly the life span of mice in an orthotopic in vivo model of A549; the combination of the anti-IGF-IR antibody with an anti-EGFR antibody was superior to the Vinorelbine combination. The present results indicate that the humanized anti-IGF-IR antibody h7C10 has a great potential for cancer therapy when combined with either a chemotherapeutic agent or an antibody that targets other growth factor receptors, such as the epidermal growth factor receptor. [source] Meta-analysis: The efficacy and safety of monoclonal antibody targeted to epidermal growth factor receptor in the treatment of patients with metastatic colorectal cancerJOURNAL OF DIGESTIVE DISEASES, Issue 4 2009Fang NIE OBJECTIVE: To evaluate systematically the efficacy and safety of anti-epidermal growth factor receptor (EGFR) monoclonal antibody added to a chemotherapeutic regimen in the treatment of patients with metastatic colorectal cancer (mCRC). METHODS: Eligible articles were identified by searching electronic databases. All randomized trials comparing the arm with an anti-EGFR monoclonal antibody to the arm without an anti-EGFR monoclonal antibody during the treatment of mCRC were included. A statistical analysis was performed with Review Manager 4.2.8. RESULTS: Seven randomized trials (n= 4186) were identified. The pooled response rates were 25.4% and 17.6% by intention-to-treat analyses for patients with or without an anti-EGFR monoclonal antibody, respectively, the OR was 3.36 (95% CI 1.42,7.95); the incidence of grades 3,4 adverse events were 71.2% and 54.3% for two groups, respectively, the OR was 2.23 (95% CI 1.74,2.86). The incidence of diarrhea, skin toxicity, hypomagnesemia was 62.3% versus 55.7%; 79.3% versus 19.7%; 27.2% versus 5.6%; and the summary OR was 1.36 (95% CI 1.03,1.80); 33.47 (95% CI 14.81,75.61); 6.73 (95% CI 3.84,11.82), respectively. CONCLUSION: Our results confirmed that monoclonal antibody targeted to EGFR could be effective in increasing response rates and could be a key therapeutic agent in the optimal treatment of mCRC, despite a moderate increase in grades 3,4 adverse events. [source] Effect of Radiation Techniques in Treatment of Oropharynx CancerTHE LARYNGOSCOPE, Issue 4 2008Kyle E. Rusthoven MD Abstract Objectives: To compare the toxicity and outcomes of three radiotherapy techniques,three-dimensional conformal (3D-RT), accelerated fractionation with concomitant boost (AFxCB), and intensity modulated radiotherapy (IMRT),in the combined modality treatment of stage III,IV squamous cell carcinoma (SCC) of the oropharynx. Study Design: Retrospective review. Methods: Between 1998 and 2007, a total of 87 patients were treated; 23 were treated with 3D-RT, 32 with AFxCB, and 32 with IMRT. Systemic therapy consisted of platinum-based chemotherapy in 81 and anti-epidermal growth factor receptor (anti-EGFR)-targeted therapy in 6 cases. Median radiotherapy doses were 70Gy with 3D-RT, 72Gy with AFxCB, and 69.3Gy with IMRT. Locoregional control, survival outcomes, and feeding tube (PEG) dependence were compared using log-rank method. The incidence of acute mucositis and skin reaction, and grade ,2 xerostomia at 6, 12, and 18 months after radiotherapy was compared using Fisher's exact test. Results: Median follow-up was 24 months (range 3 to 103 months) for living patients. Two-year overall survival (OS), disease-free survival (DFS), and locoregional control (LRC) were 77.3%, 69.5%, and 86.4%, respectively. There was a trend toward improvement in LRC in patients treated with IMRT. Acute grade ,3 skin and mucosal toxicity were significantly lower with IMRT compared to AFxCB (P < .001). Grade ,2 xerostomia was significantly reduced with IMRT compared to AFxCB and 3D-RT (P < .001). There was no difference in the actuarial rate of PEG dependence (P = .96). Conclusions: Compared to AFxCB and 3D-RT, IMRT confers an improvement in toxicity and appears to have similar efficacy in patients with SCC of the oropharynx. [source] | ||||||||||