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Clinical trials designed and led by Professor Chris Twelves (University of Leeds) showed eribulin to be the first single agent cytotoxic to prolong survival in women with heavily pre-treated metastatic breast cancer (MBC).
Eribulin has been approved by European, U.S. and other regulatory authorities since 2010. Cancer treatment guidelines in the U.S., Europe and elsewhere now recommend eribulin. Sales of eribulin generated many millions of pounds in the first full year following approval. Already tens of thousands of women have been treated with eribulin, who collectively have gained up to ten thousand added life years. The U.S. regulatory authorities have advocated the EMBRACE trial design for future trials.
Colorectal cancer is a common disease, which frequently causes death or morbidity, either because of failure to control the primary tumour or failure to prevent distant metastases. Leeds researchers have devised new treatment approaches using chemotherapy and radiotherapy and tested them in large randomised controlled trials which have led to major changes in clinical practice in the management of rectal cancer and advanced colorectal cancer (aCRC), driving clinical decision-making and improving outcomes for patients. This includes better-evidenced treatment for elderly patients and patient stratification on the basis of molecular biomarkers.
Research conducted by a multidisciplinary team of oncologists and scientists at the University of Southampton has driven major advances in lymphoma care, leading to the development and standardisation of effective new antibody treatments and optimal drug regimens. Through their direction of international clinical trials, they have influenced care for Hodgkin and Burkitt lymphoma in the UK and internationally, affecting all stages of patient-experience from diagnosis to treatment. Their findings underpin significant improvements in survival and quality of life for the 14,000 people affected by lymphoma in the UK each year.
Temozolomide is a major UK anti-cancer drug development success story. Following chemical synthesis at Aston University, early clinical evaluation of temozolomide carried out at Imperial College optimised how temozolomide was scheduled and delivered to patients to ensure maximum efficacy balanced acceptable side effects. Imperial's early trials demonstrated how the drug could be used effectively to treat patients with a type of brain cancer, glioma, and was pivotal to its subsequent market licensing. ESMO and NICE guidelines recommend temozolomide for use in patients with recurrent glioma and for patients with newly diagnosed Grade IV glioma. Glioma is a relatively rare cancer yet annual sales of temozolomide have been in excess of £900 million per year since 2009. Temozolomide given during and following radiotherapy is now standard of care for glioma and has improved survival compared to previous treatments or radiotherapy alone.
University of Glasgow research has led to the adoption of first-line chemotherapy for ovarian cancer, which has improved patient survival by 11% and has been used to treat 66% of women with ovarian cancer since January 2011 in the West of Scotland Cancer Care Network alone. These therapies are recommended by guidelines for ovarian cancer treatment in the USA, Europe and the UK. The USA guidelines are disseminated to 4.3 million people worldwide and the European guidelines reach 15,000 health professionals. The UK guidelines are used to identify those drugs that are funded by the NHS and used in NHS hospitals.
Malignant pleural mesothelioma (MPM) is a treatable but incurable cancer that originates in the cells lining the lungs. Over 14,000 people worldwide are diagnosed annually with MPM. Antifolates are often used in cancer therapy, but side effects are a major issue. A retrospective analysis of cancer trials and phase 1 trial of MPM patients, carried out by Newcastle in collaboration with Eli Lilly Pharmaceuticals, determined that plasma homocysteine levels were a good predictor of drug toxicity in cancer patients treated with the antifolate pemetrexed, and that this drug was well tolerated by patients with low homocysteine levels. It was also determined that pemetrexed treatment should be supplemented with vitamin B12 as well as folic acid, to reduce drug toxicity. Ultimately, this permitted the continued development of pemetrexed, which otherwise would have been too toxic for clinical use. It is now the only licensed drug for MPM treatment in combination with platinum-based chemotherapy.
Researchers at the University of Manchester (UoM) have made a significant impact nationally and internationally on improving the outcome for children with acute lymphoblastic leukaemia (ALL) (~450 pa in the UK). The changes in clinical practice based on our research are now national standards of care for children with de novo and relapsed ALL in the UK and Ireland. Other international groups have adopted key findings from the results of our frontline trials. Our relapse protocol for childhood ALL underpins European and North American strategy for the management of relapsed disease.
Neuroblastoma is a paediatric cancer that arises from the sympathetic nervous system. The average age at diagnosis is 18 months and the disease accounts for approximately 15% of all childhood cancer-related deaths. Determining optimal treatment for individual patients is crucial for increasing chances of survival and for reducing side effects of chemotherapy and radiotherapy. Newcastle-led research identified unbalanced 17q gain as the most common segmental chromosomal abnormality (SCA) in patients with neuroblastoma; this was present in more than 50% of patients. Gain of 17q is now one of the key SCAs used to determine treatment for patients in a European neuroblastoma trial and in UK treatment centres. Newcastle research also led to the development of a simple diagnostic test for the detection of the main SCAs in neuroblastoma.
Muscle invasive bladder cancer is the sixth most common cancer and remains a major cause of death and suffering worldwide. The standard treatment for advanced bladder cancer has been surgical removal of the bladder (cystectomy) which is associated with considerable morbidity. Many (20%) patients are elderly, with significant co-morbidities and hence are high risk for a major operation. In the past patients who were not able to undergo surgery were offered palliative radiotherapy. Research at the University of Birmingham has shown that the addition of low toxicity chemotherapy to radiotherapy is as effective as cystectomy in controlling disease progression and has minimal impact on bladder function. This new approach is an excellent alternative to cystectomy and has been adopted as a new standard of care thus demonstrating considerable impact on clinical practice and patient outcome.
The Million Women Study of 1.3 million UK women over the age of 50, coordinated by the Cancer Epidemiology Unit at Oxford, has established the relationship between hormone replacement therapy (HRT) and breast, endometrial, and ovarian cancer, and has had a dramatic effect on HRT prescription patterns and prescription guidelines worldwide. This has had a major impact on women's health. Prior to the study, one third of UK women aged 50-64 were using HRT. The marked decline in HRT use following publication of the study's findings has led to a reduction in the incidence of breast cancer among menopausal women.