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Bowel cancer is the third most frequently diagnosed cancer worldwide. University of Glasgow researchers have established Xeloda (an oral 5-fluorouracil precursor) and XELOX (a chemotherapeutic regimen combining Xeloda with oxaliplatin) as highly effective, targeted therapies for patients with bowel cancer. Since 2008, European regulatory approval of these therapies has been incorporated into major international clinical guidelines. The research has transformed patient care by improving the treatment experience, with more convenient dosing schedules and fewer side effects compared with previous chemotherapy procedures. Xeloda and XELOX have transformed chemotherapy for bowel cancer and decreased therapeutic costs, potentially saving around £4,762 (Xeloda) and £947 (XELOX) per patient for the NHS.
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.
Bladder cancer is the fifth most common form of cancer, with over 70% of cases presenting as non-muscle invasive bladder carcinomas (NMIBC). Research in the Institute of Cancer Therapeutics at the University of Bradford led to the evaluation of Apaziquone (EO9) in phase II clinical trials against high risk NMIBC in The Netherlands, and two multi-centre phase III clinical trials involving 106 centres across the USA, Canada and Europe. A total of 1,746 patients with low or high risk NMIBC received EO9 and significant reductions in the rates of recurrence at two years have been reported. Our research has impacted upon the health and welfare of patients with NMIBC.
As part of a 20 year partnership with AstraZeneca, Professor John Robertson, University of Nottingham, has made the largest and most consistent contribution by a clinical academic to the development of the most recent endocrine agent licensed for breast cancer, fulvestrant (Faslodex®). [text removed for publication]. Since 2008, fulvestrant 250mg has continued to be registered and launched in a number of countries based on Robertson's work, and Robertson has enhanced the clinical uptake of fulvestrant 250mg through training. His research has also been instrumental in the development and uptake of the more efficacious fulvestrant 500mg, including registration in 2010.
Clinical trials are costly to the pharmaceutical industry and public funding bodies, require major commitment from volunteer patients and take significant time to lead to patient benefit. Adaptive designs are one approach which seeks to improve the efficiency of such studies. Statistical research at Reading has led to novel methodology for the design and analysis of clinical drug trials within the framework of adaptive designs which has the potential to reduce the time taken for effective drugs to reach the market and thus benefit specific patient groups. To date the research has had impact in three major ways: i) it has been adopted by pharmaceutical companies as a means of improving the efficiency of their clinical trials, ii) the research has been cited in the regulatory guidance on adaptive clinical trial design, and iii) it has increased awareness by clinicians and other medical professionals of the potential benefit of the adaptive design methodology to their patient groups. Hence, the research has influenced industry, regulatory and health professionals with potential significant economic benefit and improved outcome for patients.
Cancer is a widespread deadly disease; annually, one million new breast cancers are diagnosed globally. Endometriosis is a poorly understood disorder, with 80 million patients worldwide. Current therapies for both are inadequate and discovery of new drugs is critical. The Bath group has pioneered identification of new targets and designed two "first-in-class" clinical drugs. The Bath/Imperial College spin-out company Sterix (subsequently acquired by a major pharmaceutical company) has translated them into patients and to the pharmaceutical industry. The steroid sulfatase inhibitors, Irosustat and J995 have entered eighteen clinical trials worldwide in patients with these hormone-dependent diseases, with several ongoing since 2008. Disease was stabilised for cancer patients; the advanced clinical evaluation of both drugs is in progress.
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.
Dalgleish proposed a programme to develop thalidomide analogues for their immunomodulatory and anti-neoplastic actions. Working with a small start-up company, Celgene, several analogues including lenalidomide and pomalidomide were developed and entered clinical trials. Both drugs significantly prolong patient survival in myeloma and myelodysplasia and have received FDA and NICE approval for these purposes. Celgene has grown into a large multi-national company with over 5000 employees. Lenalidomide sales were $3.8 billion in 2012.
Lung cancer is the commonest cause of cancer-related mortality worldwide. The University of Manchester (UoM) Lung Cancer Group has generated insights that underpin new standards of care in the treatment of advanced, metastatic small cell (SCLC) and non-small cell lung cancer (NSCLC), contributed to the results required for licensing of new drugs and secured approval for new treatment regimens now in routine clinical use internationally. Key contributions include an increase in survival of 23% in advanced NSCLC with the use of chemotherapy and doubling one-year survival from 13% to 27% in patients with incurable, extensive stage SCLC by the use of prophylactic cranial irradiation. The Group's research has impacted on outcomes for thousands of patients worldwide.
Newcastle University research discovered the first potent inhibitors of the DNA repair enzyme poly (ADP-ribose) polymerase 1 (PARP-1) through medicinal chemistry and preclinical work leading to first-in-man clinical studies. This research led to the development of Rucaparib, an agent that inhibits the ability of cancer cells to survive drug treatments or radiotherapy. As a result of Newcastle's research a further 8 PARP inhibitors are in development. Major pharmaceutical companies have invested an estimated $385 million in clinical trials, with at least 7000 patients enrolled in PARP inhibitor trials since 2008. Cancer patients worldwide have already been successfully treated with these new anti-cancer drugs.