A feature headline in ‘The Times’ (Saturday 12th November) reading “Don’t be put off by delays in cancer – it is no longer a death sentence” carried an upbeat message about new treatments alongside reporting some of the realities of NHS care. New treatments get headlines but research needs to break ground in new ways if all patients’ ambitions are to be truly realised.
There is a rising feeling among those who treat cancer, and among experienced patient advocates, that an end is in sight for the days of chemotherapy as a routine treatment for advanced cancer.
The use of new technologies such as immunotherapy to stimulate the immune system, therapies targeted at specific genetic mutations in a cancer, and other interventions created from the profile of an individual patient’s tumour, are rapidly spreading and the expertise in administering and managing such treatments is growing. These stories get the headlines.
There is also a realisation that a therapy gap is appearing. These development advances are not yet reaching some cancers although both academic and pharmaceutical researchers are working hard to fill that gap.
One such example is a group of rare cancers known as sarcomas. These are cancers of connective tissue with which about 5,000 patients are diagnosed each year in the UK – about 1.5% of all cancers. Generally these people are treated in specialist units at hospitals associated with academic cancer research centres. There are over 100 known sub-types of sarcoma all with some very different characteristics. Primary bone cancers are sarcomas, there are sarcomas of muscles, tendons, fatty tissue, nerve systems and blood vessels. This variation means that numbers diagnosed with any one sarcoma are small and this presents real challenges to researchers of the new treatments.
While surgery is often curative and is the usual treatment when first diagnosed, chemotherapy is still the mainstay of treatment for advanced disease. Some sarcomas will recur and patients who are diagnosed late will often get advanced disease, either through tumours recurring locally to the original site or spreading to distant organs, often the lungs. This advanced disease is rarely curable, especially in more elderly patients, many of whom will decide not to have further treatment. While there is little reliable data the number of patients living for five years in this state, even with treatment, is under 5% of those treated. Many will have toxic chemotherapy to try and hold the disease back, often hoping to get a cure, but this rarely happens.
Recognising this challenge, a researcher from the Netherlands has developed a clinical trial, working with a group of patient advocates from the UK and Holland, to consider a question which oncologists everywhere seem scared to voice – could proper supportive care in advanced disease actually be better for patients than aggressive high-doses of toxic chemicals given with the intention of cure even when there is little chance of that happening?
The EORTC TOLERANCE trial has already launched in Cyprus and Jordan. It will be available in selected UK hospitals in the New Year. EORTC is the European Organisation for the Research & Treatment of Cancer. It is a charity based in Brussels and is not associated with the European Union. It runs international clinical trials right across the world and gets funding for its studies from charitable sources, pharmaceutical companies, governments and organisations like the UK’s National Institute for Health Research (NIHR). Cancer Research UK is also a frequent UK partner.
The TOLERANCE study breaks new ground by making quality-of-life the principle outcome being assessed, using data provided by patients themselves to measure this. Clinical studies usually rely on measurements from scans and laboratory tests, together with observed data from doctors, nurses and other clinicians. By taking the route of using ‘patient reported outcomes’ the study’s Chief Investigator, Professor Winette van der Graaf, believes we will discover whether low-doses of chemotherapy can maintain a patient’s ability to live a near-normal life without very toxic side-effects. She believes this will be better for patient survival, both in its quality and perhaps its quantity too, because the study also looks at clinical data on disease progression and survival.
The first study of this kind took place in the USA more than 12 years ago. Dr Jennifer Temel from Boston led a study on patients with advanced lung cancer comparing standard (toxic) treatment with standard treatment plus intense palliative and supportive care. Survival was three months longer among those receiving the palliative care. Treatment of lung cancer has advanced so much in the intervening years with targeted therapy and immunology that these results are now seen as irrelevant for lung cancer but the overall questions this study raised still persist.
The principle that supportive care brings benefits to patients with a terminal diagnosis is one which is promoted by many patients and non-medical professionals but rarely prioritised among oncologists. Professor van der Graaf is not breaking new ground with the TOLERANCE study but she is listening to patients and bringing an innovative idea to fruition. She is an influential advocate, acknowledged as one of the leaders in cancer research and President of the EORTC, so her message and this study will get noticed.
Patient reported outcomes (known as PROs) is a fast-developing area of clinical research. Academically developed and clinically validated questionnaire tools and data gathering methods are now available which enable a research study to look reliably at how the patient sees issues such as pain, fatigue or their own ability to function socially. Drug regulators are increasingly asking to see such data so they can gain a better picture of treatment side effects and thus a more complete understanding of how a new drug performs before they authorise it for routine clinical use. Drug developers are taking steps to reduce toxicity and increase tolerability of new drugs, which alongside greater effectiveness means that the new drugs coming into clinics are easier for the patient to take.
Whether such new drugs can be developed for all cancers remains an as yet unanswered question. Scientists are certainly working with that aim in mind. A major project at the Institute of Cancer Research in Sutton is looking at sarcoma, bringing together researchers in hospitals across Europe, in the hope that new treatment opportunities can be identified and ways of actually using them can be developed. It will take time: this is a seven year project.
At some point in the future that headline in ‘The Times’ may come true for all cancers and meanwhile its optimism is admirable. Always remember that there is another side to every health story.
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Temel lung cancer paper
ICR Sarcoma Accelerator Project
Roger Wilson paper on PROs
Roger Wilson is a sarcoma patient. He is a journalist and TV producer by background but is now a patient advocate in cancer research.