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World Journal of Experimental Medicine 2014年第4期4卷 58-67页

作者： antonia digklia Ioannis A Voutsadakis Department of Medical Oncology University Hospital of Lausanne1011 LausanneSwitzerland Division of Medical Oncology Department of Internal MedicineSault Area HospitalSault Sainte MarieOntarioON P6B 0A8Canada Division of Clinical Sciences Northern Ontario School of MedicineSudburyOntarioON P6B 0A8Canada

Chemotherapy given in a metronomic manner can be administered with less adverse effects which are common with conventional schedules such as myelotoxicity and gastrointestinal toxicity and thus may be appropriate for older patients and patients with decreased performance status. Efficacy has been observed in several settings. An opportunity to improve the efficacy of metronomic schedules without significantly increasing toxicity presents with the addition of anti-angiogenic targeted treatments. These combinations rational stems from the understanding of the importance of angiogenesis in the mechanism of action of metronomic chemotherapy which may be augmented by specific targeting of the vascular endothelial growth factor(VEGF) pathway by antibodies or small tyrosine kinase inhibitors. Combinations of metronomic chemotherapy schedules with VEGF pathway targeting drugs will be discussed in this paper.

关键词： Metronomic chemotherapy Vascular endothelial growth factor Angiogenesis Bevacizumab Vascular endothelial growth factor receptor

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为变形食道的有鳞的房间癌症的指向的治疗

World Journal of Gastrointestinal Oncology 2013年第5期5卷 88-96页

作者： antonia digklia Ioannis A Voutsadakis Centre Pluridisci-plinaire d’Oncologie Centre Hospitalier Universitaire Vaudois

Squamous cell carcinoma, one of the two major subtypes of esophageal carcinomas, constitutes the great majority of tumors in the upper and middle third of the organ. Declining in incidence in western countries, it continues to be a significant public health problem in the far east. Targeted treatments are novel therapies introduced in the clinical therapeutic armamentarium of oncology in the last 10-15 years. They represent a rational way of treating various cancers based on their molecular lesions. Although no such agent has been approved so far for the treatment of esophageal squamous cell carcinomas (ESCC), several are in clinical trials and several others have displayed pre-clinical activity that would justify the efforts and risks of pursuing their clinical development in this disease. This paper discusses some of these targeted agents in more advanced development in metastatic ESCC, as well as some promising drugs with pre-clinical or initial clinical data in the disease.

关键词： Esophageal carcinoma Squamous Targeted therapies Clinical trials Epidermal growth factor receptor Vascular endothelial growth factor receptor Mammalian target of rapamycin

Advanced gastric cancer:Current treatment landscape and future perspectives

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World Journal of Gastroenterology 2016年第8期22卷 2403-2414页

作者： antonia digklia Anna Dorothea Wagner Departement d’Oncologie Centre Hospitalier Universitaire Vaudois

Gastric cancer currently ranks fourth in cancer-related mortality worldwide. In the western world, it is most often diagnosed at an advanced stage, after becoming metastatic at distant sites. Patients with advanced disease(locally advanced or metastatic) have a somber prognosis, with a median overall survival of 10-12 mo, and palliative chemotherapy is the mainstay of treatment. In recent years, novel approaches using inhibition of human epidermal growth factor receptor 2(HER2) have demonstrated significant improvements in progression-free and overall survival, compared with chemotherapy alone, in first-line treatment of patients with overexpression of HER2. In addition, both second-line chemotherapy and treatment with the vascular endothelial growth factor receptor-inhibitor ramucirumab demonstrated significant benefits in terms of overall survival, compared with best supportive care, in randomized studies. Moreover, ramucirumab in combination with chemotherapy demonstrated further significant benefits in terms of progression-free and overall survival, compared with chemotherapy alone, in second-line treatment for patients with metastatic gastric cancer. A recently published molecular classification of gastric cancer is expected to improve patient stratification and selection for clinical trials and provide a roadmap for future drug development. Nevertheless, despite these developments the prognosis of patients with advanced gastric cancer remains poor. In this review we discuss current standards of care and outline major topics of drug development in gastric cancer.

关键词： Gastric cancer Phase Ⅲ Clinical trials Chemotherapy Targeted therapy Perspectives

Eribulin for heavily pre-treated metastatic breast cancer patients

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World Journal of Experimental Medicine 2015年第3期5卷 194-199页

作者： antonia digklia Loannis A Voutsadakis Department of Oncology University Hospital of Lausanne Division of Medical Oncology Department of Medicine Sault Area Hospital Division of Clinical Sciences Northern Ontario School of Medicine

AIM: To discuss treatment with eribulin in clinical practice outside a clinical ***: Archives of patients treated for metastatic breast cancer were reviewed and 21 patients treated with the new chemotherapeutic eribulin mesylate, a synthetic analog of a natural marine product, were identified. Information on patients' characteristics and treatment outcomes was extracted. Treatment with eribulin mesylate was initiated at the recommended dose of 1.4 mg/m2 on days 1 and 8 of a 21-day cycle in 17 patients and at a decreased dose of 1.1 mg/m2 on days 1 and 8 of a 21-day cycle in 4 patients due to comorbidities and frailty. Efficacy of the drug was evaluated using the revised Response Evaluation Criteria in Solid Tumors criteria. Progression-Free Survival and overall survival(OS) were calculated using the Kaplan-Meier method starting from the date of eribulin therapy initiation to the date of disease progression documentation or death, ***: The median age of patients at the time of eribulin mesylate treatment was 53 years(range 34-75). Sixteen patients had estrogen receptor(ER) and/or partial response(PR) positive disease and 5 had ER/PR negative disease(all triple negative). Eight patients had received 2 or 3 previous lines of chemotherapyfor metastatic disease and 13 patients had received 4 or more lines of treatment. The median number of cycles of eribulin received was 3(range 1-16 years). All patients, except one, discontinued treatment due to progressive disease and one patient due to adverse effects. Six patients had a dose reduction due to side effects. All patients had progressed at the time of the report with a median time to progression of 3 mo(range 1 to 14 mo). Fifteen patients had died with a median OS of 7 mo(range 1-18 mo). Six patients were alive with a median follow-up of 13.5 mo(range 7 to 19 mo).CONCLUSION: This series of patients confirms the activity of eribulin in a heavily pre-treated metastatic breast cancer population co

关键词： Breast cancer Metastatic Eribulin Case series Retrospective Treatment