NE Oncology Issue – November 2006
The Roche-funded trial comparing XELOX to FOLFOX is the largest trial ever done for colorectal cancer, involving more than 2,000 patients in British and Spanish clinics. This is also the first data for first-line metastatic disease showing the benefit of adding bevacizumab to FOLFOX. However, the clinical improvement in survival was not very impressive, even if it was significant. We know from preclinical studies that treatment with bevacizumab should be maintained after chemotherapy in order for disease control to be maintained. In the previous registration trial using bevacizumab in conjunction with IFL chemotherapy, most patients continued bevacizumab after chemotherapy discontinuation, until disease progression. In this study, however, most patients stopped using bevacizumab after chemotherapy ended. This could account for the smaller than expected result. Also, an imbalance in randomization was noted – the patients in the bevacizumab arm had an unanticipated shorter time to recurrence after their previous surgery or adjuvant treatment, possibly implying more aggressive disease, which may have biased results.
We may now comfortably substitute oral capecitabine for infusional 5-FU (i.e., XELOX in lieu of FOLFOX) in the advanced disease setting, and future trials will need to address the benefit of bevacizumab when continued as a maintenance treatment beyond chemotherapy and until progression.
Cetuximab is an expensive drug that has been approved in Canada but is not yet marketed. The take home message from the cetuximab study by Sastre et al. was that the response rates for first-line monotherapy were modest at around 15% and very similar to what has been observed in salvage therapy. Cetuximab clearly has significant activity, however, in combination with irinotecan in the third-line setting. The side effects and toxicity of panitumumab were manageable in the salvage setting. The suggestion by the commentator in this session was that perhaps cetuximab is favoured by a larger body of evidence due to the larger number of trials performed with this agent to date; however, panitumumab may have the edge in terms of side effects and toxicity. In our clinic, we have been quite excited about panitumumab because we have had good results with it in our patients (on a clinical trial) and the common skin toxicities such as the rash are quite manageable. As in the case of erlotinib, the ideal management of the rash is not yet well defined, yet simple topical therapies are rarely helpful; corticosteroids can occasionally be very effective (oral or topical) and most severe cases respond well to temporary withholding of therapy and re-challenge.
We would like to encourage all of our Canadian centres for cancer treatment to participate in ongoing clinical trials for these new agents, particularly for panitumumab, because these studies are already running in Canada. The overall response rates for both agents are
modest and short-lived, so the evidence thus far for these biological agents suggests that they have a small degree of anticancer activity that is probably best explored in combination chemotherapy. They may also be of value in older people who can’t tolerate chemotherapy.
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.
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.
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.
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.
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.