Delivering the right treatment to the right patient at the right time.
Adjuvant therapy is given after surgery in order to decrease the risk of recurrence and improve overall long term survival. Adjuvant therapy can comprise cytotoxic and non-cytotoxic drugs as well as radiotherapy, the latter being of great interest for other Groups within the Department of Oncology.
Great progress has been made in the adjuvant colorectal cancer field over the last 25 years as we can now save a further 15-20 lives per 100 patients treated compared with surgery alone. However treatment is often delivered at great cost, both in terms of financial cost in a resource restricted environment, and toxic cost in terms of morbidity and mortality of patients undergoing such treatment. Therefore it is imperative that we not only improve the panoply (array) of drugs we can offer but also refine our ability to predict which patients will gain most benefit from which drugs. Additionally we need to predict which patients will suffer greatest toxicity, allowing us to dose reduce drugs a priori, or in some cases to avoid certain drugs altogether.
Throughout all of our large scale trials we collect blood and DNA for genetic profiling and also tumour tissue. This allows us to carry out highly powerful translational research and lends us the scope to define the biomarkers as outlined above. In addition to furnishing our own research, these huge biobanks with extremely clean and reliable clinical data can be mined by other researchers.
Recent and planned trials include:
- QUASAR2: Assessing the addition of bevacizumab (Avastin®) in the adjuvant treatment of colorectal cancer.
- SCOT: Assessing whether 3 months of adjuvant therapy can give equivalent efficacy compared to the standard 6 months of chemotherapy in the adjuvant treatment of colorectal cancer, thereby reducing toxic and financial cost.
- COLOSELECT: A planned multinational trial looking at the efficacy of aspirin and vitamin D in biomarker-selected populations of colorectal cancer.
Rachel Kerr is a medical oncologist and Associate Professor of Gastrointestinal Oncology in the Department of Oncology and at Oxford University Hospitals NHS Trust within the colorectal cancer multidisciplinary team. Rachel holds a UK Department of Health Fellowship, and is Clinical Director of the Phase 3 Trials at the Oncology Clinical Trials Office (OCTO) based within the Department. OCTO aims to drive the practical application of high-quality clinical research into innovative and effective cancer therapies and prevention strategies and has recruited almost 10,000 patients into clinical trials in the past 10 years.
A candidate gene study of capecitabine-related toxicity in colorectal cancer identifies new toxicity variants at DPYD and a putative role for ENOSF1 rather than TYMS.Rosmarin D, Palles C, Pagnamenta A, Kaur K, Pita G, Martin M, Domingo E, Jones A, Howarth K, Freeman-Mills L, Johnstone E, Wang H, Love S, Scudder C, Julier P, Fernández-Rozadilla C, Ruiz-Ponte C, Carracedo A, Castellvi-Bel S, Castells A, Gonzalez-Neira A, Taylor J, Kerr R, Kerr D, Tomlinson I. Gut. 2014 Mar 19. doi: 10.1136/gutjnl-2013-306571. [Epub ahead of print]
'Toxgnostics': an unmet need in cancer medicine.Church D, Kerr R, Domingo E, Rosmarin D, Palles C, Maskell K, Tomlinson I, Kerr D. Nat Rev Cancer. 2014;14(6):440-5
*Genetic Markers of Toxicity From Capecitabine and Other Fluorouracil-Based Regimens: Investigation in the QUASAR2 Study, Systematic Review, and Meta-Analysis. Rosmarin D, Midgley RS, Kerr DJ, Tomlinson I et al. J Clin Oncol. 2014 ;32(10):1031-9
*Evaluation of PIK3CA Mutation As a Predictor of Benefit From Nonsteroidal Anti-Inflammatory Drug Therapy in Colorectal Cancer. Domingo E, Church DN, Sieber O, Ramamoorthy R, Yanagisawa Y, Johnstone E, Davidson B, Kerr DJ, Tomlinson IP, Midgley R. J Clin Oncol. 2013; 1(34):4297-305
Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Coxib and traditional NSAID Trialists' (CNT) Collaboration. Lancet. 2013;382(9894):769-79
Haitao Wang, Research Assistant