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Fasolo A.,Istituto Nazionale dei Tumori | Sessa C.,Oncology Institute of Southern Switzerland
Expert Opinion on Investigational Drugs | Year: 2011

Introduction: The mammalian target of the rapamycin (mTOR) signalling pathway has a central role in the regulation of cell growth, survival and angiogenesis and the frequent dysregulation of this pathway in tumor cells makes it a crucial target in the treatment of cancer. Temsirolimus and everolimus are approved for use in metastatic renal cell carcinoma and temsirolimus is also approved for mantle cell lymphoma. All three rapalogs, temsirolimus, everolimus and deforolimus, are currently being evaluated in Phase III studies in several tumors. Areas covered: This paper provides a review of the published literature on the mTOR pathway and related pathway signaling, analogs and novel mTOR inhibitors. The most recent and important data on the mTOR pathway, the role of mTOR inhibitors in cancer treatment and the current status of development of second-generation highly potent and selective mTOR inhibitors are overviewed. Expert opinion: The published data on new mTOR inhibitors are still limited, but the available preclinical results indicate that they have a potent antiproliferative activity against a broad panel of tumor cell lines, have a favorable safety profile, can obtain disease stabilization or even tumor regression and, in some cases, enhance the efficacy of other targeted or standard-of-care anticancer drugs when used in vivo in preclinical studies. © 2011 Informa UK, Ltd.

Stathis A.,Oncology Institute of Southern Switzerland | Younes A.,Memorial Sloan Kettering Cancer Center
Annals of Oncology | Year: 2015

Hodgkin lymphoma (HL) remains one of the most curable human cancers, as modern combination chemotherapy and radiation therapy cure ~80% of patients. Over the last two decades, the major efforts were focused on the development of more intensive front-line regimens for patients with advanced stage HL, decreasing the number of chemotherapy cycles and radiation therapy field and doses for patients with early-stage HL and incorporating positron emission tomography imaging in diagnostic, prognostic, and treatment planning. More recently, the improved knowledge of the molecular biology of the disease led to the development of highly active new agents, including the antibody-drug conjugate brentuximab vedotin and immune checkpoint inhibitors. Accordingly, the current efforts are focusing on incorporating these new agents into standard of care regimens, aiming at further improving cure rates, while reducing treatment-related toxicity. In this review, we will focus on the current status of HL therapy and how the development of new agents is re-shaping standard of care regimens. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Gamondi C.,Oncology Institute of Southern Switzerland | Pott M.,Clinical Research Unit | Payne S.,Lancaster University
Annals of Oncology | Year: 2013

Background: In Switzerland, if certain conditions are met, assisted suicide is not prosecuted. International debate suggests that requests for hasten death are often altered by the provision of palliative care. Aims of the study were to explore patients' reasons for choice of assisted suicide and family perceptions of the interactions with health care professionals. Patients and methods: This is a qualitative study upon 11 relatives of 8 patients cared for by a palliative care team, deceased of assisted suicide. Results: Pain and symptom burden were not regarded by patients as key reasons to seek assisted suicide: existential distress and fear of loss of control were the determinants. Most patients had made pre-illness decisions to use assisted suicide. A general need for perceived control and fear of dependency were reported as a common characteristic of these patients. Patients held misunderstandings about the nature and purpose of palliative care, and the interviewed indicated that patients did not regard provision of palliative care services as influential in preventing their decision. Conclusions: Assisted suicide was preferred despite provision of palliative care. Better understanding of the importance placed on perceived control and anticipated dependency is needed. Further research is needed to develop appropriate support for patients contemplating assisted suicide. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Valli M.C.,Oncology Institute of Southern Switzerland
Critical Reviews in Oncology/Hematology | Year: 2012

Post-mastectomy RT decreases the rate of locoregional recurrences of about 70% in all patients irrespective of age, tumor characteristics or systemic therapy. Post-mastectomy RT has to be proposed, moreover when locoregional lymph nodes are part of the PTV, if an optimal coverage of the PTV and a satisfactory sparing of the OAR could be obtained. Due to the results of meta-analysis, consensus conferences and randomized trials the long-term efficacy of RT in decreasing the risk of LRF is well established and the vast majority of women, treated with mastectomy, will benefit from it. © 2010 Elsevier Ireland Ltd.

Ghielmini M.,Oncology Institute of Southern Switzerland
Annals of Oncology | Year: 2010

Follicular lymphoma is an indolent and usually incurable disease. It has been therefore traditionally approached either by watch and wait or with single-agent treatments. The purpose was to maintain a good quality of life for a prolonged time. More aggressive regimens, including polychemotherapy, high-dose chemotherapy with stem-cell rescue and the emergence of new cytotoxic drugs have significantly improved the remission duration but could never demonstrate an impact on overall survival. In the past decade, through the addition of drugs acting on the immune system such as interferon or rituximab, the survival of follicular lymphoma patients could be improved by the range of several years. As a consequence several clinicians believe that we are near to a cure for follicular lymphoma so that the first-line treatment should be more aggressive to reach this goal. Nevertheless, at present, none of the new strategies can be shown to cure. We believe that even in the presence of many possible treatment options, watch and wait remains a good option for many patients with follicular lymphoma. When treatment is needed, chemotherapy with rituximab is the standard even though none of the chemotherapy regimens can be shown to be superior. As quality of life remains an issue, the combination of rituximab and bendamustine, a drug with high efficacy and a favourable toxicity profile, is a good new option for patients. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

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