Northern Institute for Cancer Research, Newcastle University
Sarcomas are rare tumours that account for approximately 1% of all cancers in the UK. They represent a challenge to treating clinicians as diagnosis is often delayed and the tumours are commonly in an advanced stage or have spread to other parts of the body. Current treatment approaches for these advanced tumours have shown only modest response rates of 12-24% and are associated with significant toxicity in patients. A recently completed clinical trial was designed to investigate whether a combination of the drugs gemcitabine and docetaxel results in an improved clinical outcome, as compared to standard treatment with doxorubicin. In addition, the trial also involved the collection of blood samples to look at genes that control how fast these drugs are removed from the blood stream and what happens to the drugs in the body. By investigating variations in genes between patients, we may be able to predict which patients are most likely to respond well to individual drugs, and which patients may be more likely to experience toxicity following treatment. We have identified the most important genes to study for each drug involved in the trial and blood samples have been collected from over 230 study patients. We will carry out the appropriate tests to learn about genetic variation between these patients and to investigate whether the variation seen impacts on clinical response and toxicity. It is hoped that the findings from the study will help to decide how future patients may be treated most effectively, to maximise the chance of successful response while minimising the side-effects of treatment.
The treatment of advanced soft tissue sarcoma represents a significant clinical challenge, with overall survival rates of approximately 12 months observed with current first line treatment. A clinical trial was recently completed to compare treatment of patients with the current standard approach of single agent doxorubicin or combination treatment with the chemotherapy drugs gemcitabine and docetaxel. As part of this clinical study blood samples were collected from patients before their treatment, to investigate genes that control how fast these drugs are removed from the blood stream. Differences between these genes in different patients may allow us to predict which patients are more or less likely to respond to treatment and/or experience more or less side effects associated with their treatment. We looked at differences in certain genes of interest using blood samples collected from 240 patients on the clinical trial. The results from the study identified several differences in genes between patients that appeared to be linked to a decreased chance of survival and decreased toxicity following treatment. These findings will be followed up in future clinical trials.
- Seddon, B. et al. (2017) Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastic soft-tissue sarcomas (GeDDiS): a randomised control phase 3 trial. The Lancet. Oncology 18(10). Read more: https://www.ncbi.nlm.nih.gov/pubmed/28882536
- Jamieson, D. et al. Pharmacogenetics of doxorubicin, gemcitabine and docetaxel in the GeDDiS soft tissue sarcoma trial. Poster presented at the Sarcoma UK Research Symposium. September 2016. London, UK.