The hypothesis of this study was that XRCC3 is important in the repair of cisplatin-induced damage of DNA, and that low XRCC3 expression would impair the cell’s ability to repair DNA and make cells more sensitive to cisplatin. However, they found no differences in survival regardless of the mutation status of the XRCC3 gene in assessed tumour samples, so the result failed to support their hypothesis. The decision to look at the effect of younger age combined with the presence of an XRCC3 mutation appears to be a post-hoc conclusion that should not change the interpretation of overall findings of the study. This study becomes important when we consider the prospective study presented by Rosell et al. on ERCC1, which also failed to show any improvement in the primary outcome of progression-free survival for patients whose treatment was selected on the basis of genomic profiling of ERCC1.The results do not support the hypothesis that ERCC1 status can be used to select patients’ suitability for cisplatin-based therapy. This study suffered from methodologic problems in that the investigators were unable to assess ERCC1 mutation status in a number of the patients assigned to the genotypic arm as well as the fact that many patients had withdrawn from this arm of the study post-randomization.

This series of reports highlights that if we select patients for therapy with either gefitinib or erlotinib based on mutations in the EGFR or on FISH analysis, there is a very high likelihood that they will respond to the treatment, and this does not appear dependent upon the amount of prior chemotherapy patients have received. This is very interesting data and the question now is how do we use this information in practice? Some people would suggest that based on these response rates we should only be giving EGFR TKI’s to patients who have mutations or who overexpress EGFR. There is an urgent need for prospectively designed trials to answer this question. One important study is currently comparing first-line gefitinib to platinumbased chemotherapy in a population of Asian patients carrying EGFR mutations. Another important study scheduled to begin later this year in Italy and Canada is the TORCH (Tarceva OR ChemoTherapy) trial, which will examine first-line erlotinib in a non-selected group of patients with NSCLC. Patients will be randomly assigned to either first-line therapy with erlotinib or cisplatin plus gemcitabine therapy, with a planned crossover at the time of progression. Correlative studies conducted in parallel will examine the importance of EGFR expression or mutation status on clinical outcome.

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Contributors

dr.lemonde
Manon Lemonde, MB
Associate Professor, Faculty of Health Sciences, University of Ontario Institute of Technology (UOIT
Dr. Manon Lemonde received her PhD in biomedical sciences from the Université of Montréal. She has many publications related to symptom management and social support. She has presented at oncology conferences and was also instrumental in developing workshops on fatigue in cancer. Dr. Lemonde’s oncology research interests are related to quality of life, human health resources planning in terms of recruitment and retention, and work environment.

dr-ellis
Peter Ellis, MBBS, MMed (Clin Epi), PhD, FRACP
Associate Professor in the Departments of Medicine and Clinical Epidemiology & Biostatistics, McMaster University
Chair of the Juravinski Cancer Centre Lung Disease Site Team
Executive Member of the National Cancer Institute of Canada (NCIC) Clinical Trials Group Lung Disease Site Committee Dr. Peter Ellis is a staff medical oncologist at the Juravinski Cancer Centre (JCC). He is a member of Cancer Care Ontario’s Practice Guideline Initiative, Provincial Lung Disease Site Group. He is also an investigator on several NCIC and pharmaceutical industry-sponsored multi-centre phase III clinical trials in breast and lung cancer. Dr. Ellis has a research interest in the role of the consumer in decision making, and is an investigator in several studies in this area. He is also co-principal investigator in a systematic review examining diffusion and dissemination of cancer control interventions.

dr-clemons
Mark Clemons, MB, BSc, MRCP(UK), MD
Associate Professor of Medicine and Oncology, McGill University Division of Hematology, McGill University Health Centre Head of Breast Medical Oncology, Princess Margaret Hospital
Assistant Professor, Department of Medicine, University of Toronto
Dr. Mark Clemons is a staff oncologist at the Princess Margaret Hospital, Toronto. He has published widely on the management of breast cancer, and has a research program evaluating the mechanisms of resistance and sensitivity to treatment for bone metastases and locally advanced breast cancer.

dr-cole
Dana Cole, BScPharm, ACPR, PharmD
Clinical Pharmacist and Pharmacy Residency Coordinator, Prince George Regional Hospital
Head of Breast Medical Oncology, Princess Margaret Hospital
Assistant Professor, Department of Pharmacology, University of Northern British Columbia
Clinical Assistant Professor, Faculty of Pharmaceutical Sciences, University of British Columbia
Dana Cole’s clinical interests are in supportive care, particularly anemia management, venous thromboembolism and palliative care. She has served as a reviewer for the professional development and assessment program, as a member of the advanced practitioner credentialing committee with the College of Pharmacists of BC, and as a member of the Canadian Association of Pharmacy in Oncology and the Canadian Society of Hospital Pharmacists.

dr-sehdev
Sandeep Sehdev, MD
Oncologist, William Osler Health Centre, Brampton
Dr. Sehdev is a community-focused medical oncologist at one of Canada’s largest community hospitals. He completed his fellowship at the Princess Margaret in Toronto in 1991, and his clinical practice treats most types of cancer. However, he has a keen interest in breast cancer, lung cancer, and patient education. Dr. Sehdev has been involved in breast cancer clinical trials through NCIC and BCIRG groups and has recently chaired several medical advisory board meetings on the role of hormonal therapy in breast cancer. In particular, Dr. Sehdev has been part of one of the largest and longest running breast cancer trials ever, the ATAC trial.