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Cebon J.,Austin Ludwig Oncology Unit | Cebon J.,Ludwig Institute
Asia-Pacific Journal of Clinical Oncology | Year: 2010

The discovery that the immune system can distinguish molecular targets on cancer cells has led to efforts to develop cancer immunotherapeutics that can improve the recognition and effective elimination of tumor cells. Several types of tumor antigens are recognized by T lymphocytes, which are classified according to patterns of gene expression or protein distribution. Of particular interest is the group of molecules known as cancer-germline or cancer-testis antigens. As the relationship between the immune system and cancer has become clearer, so too have the challenges in designing effective cancer immunotherapeutics: (i) antigens need to be specifically selected based on ideal characteristics, such as tissue distribution that is restricted to tumors; (ii) selected antigens need to be combined with adjuvant agents that enhance their immunogenicity and yield robust responses; (iii) vaccination should be timed to pre-empt the development of regulatory suppressive immune mechanisms; and (iv) if suppressive regulatory mechanisms do arise, specific antagonists may be needed to enhance pro-immune outcomes. These challenges are shaping current and future research in this area. © 2010 The Author. Journal Compilation © Blackwell Publishing Asia Pty Ltd. Source

Liew M.S.,Austin Ludwig Oncology Unit | Liew M.S.,Ludwig Institute for Cancer Research | Liew M.S.,University of Melbourne | Starmans M.H.W.,Ontario Cancer Institute | And 10 more authors.
Cancer Medicine | Year: 2013

Concurrent chemoradiotherapy (CCRT) has become the standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC). The comparative merits of two widely used regimens: carboplatin/paclitaxel (PC) and cisplatin/etoposide (PE), each with concurrent radiotherapy, remain largely undefined. Records for consecutive patients with stage III NSCLC treated with PC or PE and ≥60 Gy chest radiotherapy between 2000 and 2011 were reviewed for outcomes and toxicity. Survival was estimated using the Kaplan-Meier method and Cox modeling with the Wald test. Comparison across groups was done using the student's t and chi-squared tests. Seventy-five (PC: 44, PE: 31) patients were analyzed. PC patients were older (median 71 vs. 63 years; P = 0.0006). Other characteristics were comparable between groups. With PE, there was significantly increased grade ≥3 neutropenia (39% vs. 14%, P = 0.024) and thrombocytopenia (10% vs. 0%, P = 0.039). Radiation pneumonitis was more common with PC (66% vs. 38%, P = 0.033). Five treatment-related deaths occurred (PC: 3 vs. PE: 2, P = 1.000). With a median follow-up of 51.6 months, there were no significant differences in relapse-free survival (median PC 12.0 vs. PE 11.5 months, P = 0.700) or overall survival (median PC 20.7 vs. PE 13.7 months; P = 0.989). In multivariate analyses, no factors predicted for improved survival for either regimen. PC was more likely to be used in elderly patients. Despite this, PC resulted in significantly less hematological toxicity but achieved similar survival outcomes as PE. PC is an acceptable CCRT regimen, especially in older patients with multiple comorbidities. © 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. Source

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