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Tarazona N.,GI and Lymphoma Unit | Navarro L.,University of Valencia | Cejalvo J.M.,University of Valencia | Gambardella V.,University of Valencia | And 4 more authors.
OncoTargets and Therapy | Year: 2015

Ewing’s sarcoma is a rare and highly aggressive cancer most frequently arising in people under 20 years of age. We report an uncommon case of primary paraesophageal Ewing’s sarcoma in a 25-year-old male harboring the infrequent EWSR1/ERG fusion transcript with multiple splice variants coexisting in the same tumor. The patient was totally refractory to chemotherapy and died 17 months after diagnosis. We underscore the need for better understanding of the molecular pathogenesis of the disease and improved systemic therapy options. © 2015 Tarazona et al.


Khan K.H.,GI and Lymphoma Unit | Yap T.A.,Drug Development Unit | Yan L.,Merck And Co. | Yan L.,Peking University | Cunningham D.,GI and Lymphoma Unit
Chinese Journal of Cancer | Year: 2013

The phosphoinositide 3-kinase-AKT-mammalian target of rapamycin (PI3K-AKT-mTOR) pathway is a frequently hyperactivated pathway in cancer and is important for tumor cell growth and survival. The development of targeted therapies against mTOR, a vital substrate along this pathway, led to the approval of allosteric inhibitors, including everolimus and temsirolimus, for the treatment of breast, renal, and pancreatic cancers. However, the suboptimal duration of response in unselected patients remains an unresolved issue. Numerous novel therapies against critical nodes of this pathway are therefore being actively investigated in the clinic in multiple tumour types. In this review, we focus on the progress of these agents in clinical development along with their biological rationale, the need of predictive biomarkers and various combination strategies, which will be useful in counteracting the mechanisms of resistance to this class of drugs.


Hawkes E.,GI and Lymphoma Unit | Okines A.F.C.,GI and Lymphoma Unit | Papamichael D.,Bank of Cyprus Oncology Center | Rao S.,GI and Lymphoma Unit | And 5 more authors.
European Journal of Cancer | Year: 2011

Introduction: Systemic chemotherapy improves survival in oesophagogastric cancer however no standard second-line regimen exists due to a paucity of randomised data. Docetaxel combined with irinotecan (DI) provides a suitable option due to the lack of cross-reactivity with first-line therapeutics and a tolerable toxicity profile. Methods: We retrospectively reviewed a cohort of patients with advanced oesophagogastric cancer in two institutions treated with the combination of docetaxel 35 mg/m 2 plus irinotecan 60 mg/m 2 day 1 and day 8 every 21 days, following progression with first-line platinum-based therapy. Results: Between January 2000 and September 2009, 41 eligible patients were identified. Median age was 58 years, male:female 25:16, adenocarcinoma:squamous cell carcinoma 37:4, oesophageal: oesophagogastric junction:gastric 7:10:24. Locally advanced:metastatic disease 6:35. Previous radical surgery:radiotherapy:both 6:4:7. 27/41 had progressed within 90 days of receiving platinum-based therapy. Median number of chemotherapy cycles: 3 (range 1-12). Eight patients required dose reductions due to DI toxicity. 10/28 evaluable patients had a response, median progression-free survival (PFS) was 11 weeks (95% confidence intervals (CI): 9-13 weeks) with median overall survival 24 weeks (95%CI: 12-35 weeks). No significant prognostic factors were identified. Conclusion: Weekly docetaxel combined with irinotecan has acceptable safety and modest efficacy in the second-line treatment of advanced oesophagogastric cancer. Further prospective evaluation of this regimen is warranted. © 2010 Elsevier Ltd. All rights reserved.

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