Standard chemotherapy treatment for HPV-positive throat cancer remains the most effective, study finds
A new study funded by Cancer Research UK and led by the University of Birmingham has found that the standard chemotherapy used to treat a specific type of throat cancer remains the most effective.
The findings of the trial, which aimed to compare for the first time the outcomes of using two different kinds of treatment for patients with Human papillomavirus (HPV)-positive throat cancer, are published today (November 15th) in The Lancet.
Throat cancer is one of the fastest rising cancers in Western countries. In the UK, incidence was unchanged between 1970 and 1995, then doubled between 1996 and 2006, and doubled again between 2006 and 2010. The rise has been attributed to HPV, which is often a sexually transmitted infection. Most throat cancers were previously caused by smoking and alcohol and affected 65 to 70 year old working class men. Today, HPV is the main cause of throat cancer and patients are middle class, working, have young children and are aged around 55.
HPV-positive throat cancer responds well to a combination of cisplatin chemotherapy and radiotherapy, and patients can survive for 30 to 40 years, but the treatment causes lifelong side effects including dry mouth, difficulty swallowing, and loss of taste.
The De-ESCALaTE HPV study, which was sponsored by the University of Warwick, compared the side effects and survival of 164 patients who were treated with radiotherapy and cisplatin, and 162 who were given radiotherapy and cetuximab. The patients were enrolled between 2012 and 2016 at 32 centres in the UK, Ireland, and the Netherlands. Patients were randomly allocated to be treated with radiotherapy and either cisplatin or cetuximab. Eight in ten patients were male and the average age was 57 years.
Importantly, the results found that there was very little difference between the two drugs in terms of toxicity in patients and side effects such as dry mouth, however, there was a significant difference in the survival rates and recurrences of cancer in patients taking part in the trial.
They found that the patients who received the current standard chemotherapy cisplatin had a significantly higher two-year overall survival rate (97.5%) than those on cetuximab (89.4%). During the six-year study, there were 29 recurrences and 20 deaths with cetuximab, compared to 10 recurrences of cancer and six deaths in patients who were treated with the current standard chemotherapy cisplatin.
And cancer was three times more likely to recur in two years following treatment with cetuximab compared to cisplatin, with recurrence rates of 16.1 per cent versus six per cent, respectively.
Study lead Professor Hisham Mehanna, Director of the University of Birmingham's Institute of Head and Neck Studies and Education, said: "Many patients have been receiving cetuximab with radiotherapy on the assumption that it was as effective as cisplatin chemotherapy with radiotherapy and caused fewer side effects but there has been no head-to-head comparison of the two treatments.
"Cetuximab did not cause less toxicity and resulted in worse overall survival and more cancer recurrence than cisplatin.
"This was a surprise – we thought it would lead to the same survival rates but better toxicity. Patients with throat cancer who are HPV positive should be given cisplatin, and not cetuximab, where possible."
Dr Emma King, Cancer Research UK Associate Professor in head and neck surgery at the University of Southampton, said: "Studies like this are essential for us to optimise treatments for patients. We now know that for HPV-positive throat cancer, the standard chemotherapy treatment remains the most effective option.
"However, we must keep testing new alternatives to ensure patients always have access to cutting-edge and kinder treatments. Chemotherapy and radiotherapy can leave head and neck cancer patients with long term pain and difficulties swallowing, so we should always strive to minimise side effects."
Professor Janet Dunn from the University of Warwick, whose team ran the De-ESCALaTE HPV trial, said: "In the current trend for de-escalation of treatment, the results of the De-ESCALaTE HPV trial are very important as they were not as we expected. They do highlight the need for academic clinical trials and are an acknowledgement of the key role played by Warwick Clinical Trials Unit at the University of Warwick as the co-ordination and analysis centre for this important international trial."
The patients on the De-ESCALaTE trial Steering Committee endorsed the importance of research findings.
Malcom Babb, who is also President of the National Association of Laryngectomee Clubs, said: "From a patient perspective, De-ESCALaTE has been a success by providing definitive information about the comparative effectiveness of treatment choices."
For more information please contact Emma McKinney, Communications Manager (Health Sciences), University of Birmingham, Email: [email protected] or tel: +44 (0) 121 414 6681, or contact the press office out of hours on +44 (0) 7789 921 165 or [email protected]
Notes to Editors
The University of Birmingham is ranked amongst the world's top 100 institutions. Its work brings people from across the world to Birmingham, including researchers, teachers and more than 5,000 international students from over 150 countries.
Mehanna et al (2018). 'Radiation with cisplatin or cetuximab in Human papillomavirus-related low risk oropharyngeal cancer – the De-ESCALaTE HPV trial'. The Lancet. DOI: 10.1016/ S0140-6736(18)32752-1
When the paper publishes, it can be found at http://dx.doi.org/10.1016/S0140-6736(18)32752-1
The DeESCALaTE study (Determination of epidermal growth factor receptor-inhibitor (cetuximab) versus standard chemotherapy (cisplatin) early and late toxicity events in human papillomavirus-positive oropharyngeal squamous cell carcinoma).
* The research was carried out in collaboration with Newcastle University; University Hospitals Birmingham NHS Foundation Trust; Weston Park Hospital, Sheffield; University of Warwick; St James's Institute of Oncology, Leeds; Castle Hill Hospital; Bristol Haematology and Oncology Centre; St James' University Hospital; Aberdeen Royal Infirmary; Royal Surrey County Hospital; Luke's Hospital, Dublin, with Cancer Trials Ireland and St Lukes Institute of Cancer Research; Cheltenham General Hospital; Nottingham University Hospitals NHS Trust; James Cook University Hospital; Abertawe Bro Morgannwg University Health Board; Royal United Hospitals Bath NHS Foundation Trust; University Hospital Coventry and Warwickshire NHS Trust; Western General Hospital, Edinburgh; University Medical Centre, Netherlands; Amsterdam UMC, Netherlands; Royal Marsden Hospital; Institute of Cancer Research and Royal Marsden Hospital, London; and University of Oxford
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