Category: Clinical trials

PROs at the centre of cancer care

Chemotherapy or supportive and palliative care? Its a question which oncologists are increasingly addressing with their patients. People with advanced solid tumours, that is cancers which have spread to secondary sites, are very rarely curable, although maintaining stable disease for a significant time is increasingly possible. Symptomatic treatment with the aim of delivering a high quality of life may be preferable to a so-called curative approach.

One of the communication challenges is the widespread belief that chemotherapy in these circumstances will deliver a cure. Oncologists can do their best to help patients to understand the situation but they cannot educate family and friends. Patients often lack the necessary mastery of the information or the skills to convince their family of the reality. Family pressures to undergo chemotherapy can be very real for those who are already vulnerable.

The new targeted therapies do change the picture for some patients. If your tumour carries a genetic or biological target which is treatable extra time can be bought, sometimes with few side effects, although there can be a financial cost and cure remains rare. These drug costs are becoming a significant part of the NHS cancer drugs budget and the struggle to keep costs under control is highlighting the challenge which society faces, to understand the holistic value of these treatments.

Value lies in the underlying reality that secondary solid tumours kill their host. Patients without secondary tumours usually survive their cancer. Treatment with high cost drugs to prevent secondaries is a ‘holy grail’ for pharmaceutical companies, the demand would be very profitable. Their urge for acceptance of their costly new treatments excites the media, which rarely reports the realities.

Today’s realities offer a different picture. Early diagnosis and skilled primary treatment are the surest ways of delivering better survival. The renewed NHS focus on this is welcome. Cure represents value. However, there will always be people who, for whatever reasons, present late and with secondary tumours. Proper supportive care is needed for them and the NHS is not as good at responding to this need as it could be either in primary or secondary care. Attention to value is required.

The value issue principally focuses on those with secondary tumours which develop while in follow-up or care. How does treatment affect a patient’s life, whether that is chemo, new targeted drugs, interventions such as surgery or radiotherapy, or symptomatic care. What is the balance with cost? Health economics looks at ‘cost effectiveness’ but this is more about how a patient clinically responds, and for how long, to any treatment rather than how it affects their life.

Looking to meet the modern demand for an acronym Value can be defined this way (from a patient viewpoint):

Variations in my Actual Life and Usual Experience

Attempts to look more holistically at value to capture actual life and usual experience through the lens of patient reported outcomes (PROs), are still at an early stage. The tools which have been developed so far are clumsy and the challenges of implementing them effectively are still being worked out. There are good people working on this (not enough of them are actual patients) but many research organisations give it a low priority so funding is small and progress slow.

Regulators and legislators need to step into this area. Their work is increasingly relying on good data drawn directly from patients. The oncologist and patient who today are having that difficult conversation about chemo or not need the data too. Patient Reported Outcomes are the future shape of healthcare regulation and practice. They are not a nice add-on which appeals to ethics committees, they are an essential element in the science of treating people with disease. PROs can deliver an understanding of real Value to society. They must be taken seriously.

Where next for patient involvement in research ?

A very welcome editorial in the BMJ will I hope give greater strength to the growing movement for provision of patient involvement in research.

I have been an ‘involved patient’ for 16 years. In the early days getting to understand research was the first challenge, we had no training available to us. Our professional research colleagues could hardly be more welcoming but were actually confused about how to handle us, could not recognise situations we could help with, and sometimes could not even handle the questions we asked. So we learned together.

There were a few enlightened researchers and leading doctors in those early days. It is almost unfair to pick two out for comment but they were outstanding in their recognition of the issues and in the way that they addressed them. Professor Sir Mike Richards, the first National Cancer Director, and Professor Peter Selby, the first Director of NCRN and later what is now NIHR CRN. Both realised that what they were changing was a process and that it would take time. We all wanted it to be quicker but there is an inertia in the affairs of man which means that changing established cultures can rarely be rushed.

There was a lot of pressure in the early years to demonstrate the ‘value’ of patient involvement as an intervention. By assessing its direct impact on a research project through something which may be as simple as a consent information sheet, the hypothesis was that the impact must be measurable. This question is still heard in Europe, voiced by research communities who do not want, for whatever reasons, to recognise the role that patients can play. Such assessment requires some kind of baseline against which the changed outcome can be compared. Most attempts to describe the impact of patient involvement in these terms have been trivial at best and laughable in many cases. Publication in a peer-reviewed journal is noticeably hard to find.

Patient involvement in research is about changing the processes by which research progresses. It does not change the science, although questions raised may cause design modifications by the scientists, but it modifies the environment – the timing, the nature of discussion, the emphases placed at different times, the interactions between team members etc. It will also bring in a different consideration of the impacts on patients entering the study, the ethical boundaries, the nature of communications with patients, and can play a part in deciding about data analyses and the promotion of results.

Even in the UK where patient involvement is now almost ubiquitous in healthcare research, this difference is not fully understood. Many research groups pride themselves on patient involvement which is in fact quite trivial, They involve patients in reviewing patient issues raised by their studies, reviewing consent information, sitting on Trial Management Committees, but have resisted a deeper involvement in the whole research process. That is their next step.

This puts an interesting burden on the researchers who are in such partnerships with patients. They must start to more consistently integrate their patients in everything they do. They must also report their subjective responses to these partnerships and the way they evolve so that we can build a picture of value which can help the more recalcitrant recognise the importance of involvement. We, the patients, cannot do this alone.

I welcome steps such as this week’s announcement by the BMJ that from next year it will not only require researchers to report on their patient involvement activity but also on the dissemination of their results to patients.

Every bit as important is the growing reach of the Biomed Central journal Research Involvement & Engagement. RI&E is the only peer-reviewed journal dedicated to papers on patient involvement. (I declare an interest – I am on the Editorial Board).

The moment is right for the debate about patient involvement to widen and develop on an informed basis. We have to find the mechanisms to create a common understanding of where we are today, the different models of involvement, the perceptions and expectations which we have individually and collectively based on the experiences we have had, and the reports of innovative practice and clearer thinking which have come through in the publication of papers on different implementations. We have the opportunity to define an agenda which sits comfortably with the research community and which can be implemented pragmatically, ultimately for patient benefit.

There are some underlying ‘big’ issues to address as well. One is how can involved patients hold their research partners to account, should that be necessary. Another thorny issue is should involved patients be remunerated in some way and how can this be done without conflicting with their independence.. Even if some of these issues cannot be answered they can be clearly defined and understood. Maybe some form of guidance can be offered. Contributions to the ongoing debate would always be accepted by interested journals.

Despite these complications the underlying rationale for patient involvement in research is simple. Research is a collaborative activity which should maximise quality by including representation from all those with a stake in it. The (over-used) patient mantra, ‘nothing about us without us’, probably applies here more than anywhere else.

Detecting the otherwise undetectable

The perfect pill is the one which treats the feared but undetectable illness. It leads to sales in the billions as everyone seeks to take it. Day dream profits for a pharmaceutical company, Nobel prize for the scientists behind it, new energy for the global economy … enormous potential … but we are not there yet.

The idea of testing for the otherwise undetectable cancer is here. It is only one step more to get to the day dream. The test delivers genetic mutation information, this must have pharma companies salivating. The now-detected but otherwise undetectable cancer is not treatable by non-medical means unless it is allowed to develop to the point where it is identified and treatable … unless medical therapies are developed. Demand for those pills will be huge. Genetically targeted therapies cost thousands.

Roll on the pill revolution.

Is this blood test, which got so much press coverage over the weekend, really as valuable as reports suggest? Fortunately some level heads from UK academic research were more careful when interviewed. Lets also look at it from a patient viewpoint and ask if it will serve the objective of earlier diagnosis in the way which is being suggested.

Screening was implied. Screening who, is not explained. A screening method must balance its costs against the savings created by earlier detection. This means criteria to refine those screened to the most likely people to show a positive result. Screening also has downsides. It has false negatives (failing to spot someone with cancer) and false positives (indicating cancer when there is none present). It can lead to over treatment and unnecessary long term side effects. And of course it creates anxiety – which would include those who have been diagnosed too early to be effectively treated because no tumours are visible. This will create demand for a pill.

Used in primary care the test would have value if a practitioner suspects cancer. Today such patients are sent for imaging and other tests to gather actual evidence. A blood test may do that quicker and would have particular value where symptoms are vague. It could lead to a quicker and more accurate diagnosis in cases of real uncertainty. But treatment may not necessarily start more quickly … unless a pill is available.

Before introducing the test we would have to be certain that all rare forms of cancer can be covered, maybe not immediately but quite quickly after the test becomes standard practice. Expanding eight cancers to several hundred could prove challenging. Its no use saying to a patient your vague symptoms don’t show you have one of the eight cancers if they are shortly afterwards diagnosed with a rarer cancer. From a patient viewpoint cancer is cancer, the test failed.

So once again I am finding myself appealing for context when clever medical science is discussed. The idea of a blood test providing early recognition of cancer has important implications. If the technique comes through the next stages of research showing a high percentage of accurate diagnoses, covering more cancers, with few (if any) false negatives or positives in early stage otherwise unidentifiable cancer, then we will be able to think about changes in primary care practice. The proper analysis of practical and cost issues, including the cost implications of consequent medical therapy, can then be addressed.

I think this is all a long time away and I have to ask, is a pill the real objective of this research? Society needs better ideas than this one to detect cancer earlier. Don’t day dream too soon.

We Are Stronger in Partnership

This theme is often the sub-text behind a conference combining patients and clinicians on the same agenda, but these are usually patient-led conferences and the theme rarely makes its way into professional events. When it happens it is done very cautiously, patient contributors are usually sought at the last minute, and even though the audience feedback is almost always appreciative the repeat event does not do it any better.

Out with the old and in with the new, that was the approach taken by the Rarer Cancers Europe project when developing a training course for both patients and professionals with ESMO and ESO. It was held in early December in Milan and it was a great success.

An initial plenary session on the Saturday included talks from professionals (Jean-Yves Blay, Paolo Casali, Paolo Dei Tos, Rolf Stahel) and patients (Kathy Oliver from IBTA and Francesco Di Lorenzo of ECPC). Questions came almost equally from patients and professionals in the audience.

Separate professional and patient sessions started after lunch on the Saturday. The patient programme focussed on Advocacy Issues in Rarer Cancers. The Saturday and Sunday sessions covered clinical issues – diagnosis, surgery, oncology and research. Individual clinicians and scientists came from the professional event to talk for 20-30 minutes on a defined topic and to answer questions. These sessions were lively with lots of issues and new ideas put forward by the speakers, and plenty of challenges from the advocate audience to keep them on topic and on their toes.

Meantime the professional session looked at some specific tumour types. Patients from the advocacy group attended sessions of personal interest, often raising questions which some of the professionals attending would have liked to ask but because they did not want to look ill-informed in front of their peers were too nervous to do so.

The advocacy research session was particularly lively when Dr Paolo Bruzzi (a statistician) and Dr Paolo Casali (medical oncologist) came together to talk about probability statistics in a joint session. At one point they put forward a hypothetical trial of intercessory prayer, examined how probability would affect its results, and how it would compare with a study of a more usual medical therapy. The subject of combination therapy was raised, which caught both scientific speakers unprepared. A humorous moment. It was followed by a stimulating talk from Eric Low OBE, a very experienced advocate, looking at the social, cultural, political and medical pressures to change research models and rely more on real world evidence.

The final session on Monday looked at advocacy issues, drawing on the long experience as an advocate which some members of the group had. The presentations included case studies of activities successfully undertaken by patient advocacy groups. These were listened to carefully by a couple of senior clinicians, sitting quietly at the back.

A closing short plenary summarised the weekend. These was agreement that it was a great success. Dr Casali, who led the event, deserves congratulations. The combined audience recognised the value of a parallel conference for clinical specialists and patient advocates which sets out to make maximum use of the skills and experiences of each group for the benefit of the other group. Both the planned and the unplanned interchange of audience members according to personal choice was truly valuable.

I look forward to seeing similar structures evolve in professional events everywhere. Let conference companies take note.

 

Introducing PPI in Research – Purpose, Plan, Impact

Research is not an end in itself. Many researchers and their managers might think it is but involved patients should not be trapped into this mindset.

We are patients involved in research because we believe that we can help change things for the better. We believe that better treatments can be identified by good science. We believe that better care can result from good quality research. We believe that better processes and systems can be created. We cannot do this all by ourselves, we can only do it in partnership with the professionals. They may be managers, nurses, scientists, doctors, educators, inspectors, commissioners, policy makers or politicians. Research gives us the evidence to support change.

As an involved patient you should never lose sight of this important vision, we are in the business of transforming patient care for the better. Research is a means to that end, not an end in itself.

Sadly the myopic draft standards for patient and public involvement being assembled by NIHR do not address this purpose. The view presented is all inward to the research process, nothing abut what research can achieve to support change. NIHR have acknowledged that the standards are draft and will change. A positive step, I hope the next draft will address Purpose.

Involved patients must be asking questions about Purpose, asking why a research project is being undertaken? What are the issues to be faced in extending a successful study into routine clinical practice? Researchers without clinical experience may have limited horizons and no understanding about practicalities. Patients can bring that perspective, after all usually they will have been there. There is a second PPI in our debate – Purpose, Plan, Impact.

Plan brings me to a second point, a practice I would like to see which would encourage researchers to think outside their usual boxes. Every research project should have a plain language lay summary written at the outset, even before the project is approved. It states what the Plan is. It is part of the public face of the project, on its webpage, in any patient information and consent process, and in the final study report. It makes clear what the study will achieve, for patients. As a project progresses the summary would be regularly reviewed and updated so that everyone will know how it is progressing. The lay summary should also include the why and how of implementing positive results. That should be part of the Plan even if that is expressed only as ambition. That will be how Impact is delivered.

A lay summary used in this way would hardly affect research processes but it would change the focus of research quite subtly. The project would always be associated with its ambition, its anticipated Impact. It would have PPI – Purpose, Plan, Impact.

Let us hope that the next iteration of the NIHR Standards will capture some of this quality, will look outwards not inwards, will focus on Purpose, Plan, Impact.

We don’t need PPI Standards like these?

I have worked as a patient involved in research for over 15 years now. I have been involved in clinical/medical research at just about every level possible locally, nationally and internationally. I like to think I have helped things change and the responses I have had from the professionals would seem to confirm that.

It was interesting to find out about the development of a Patient and Public Involvement Standards process being developed by NIHR (the National Institute for Health Research) and INVOLVE, the national organisation for promoting involvement in research. There is an on-line questionnaire and a website. The objective is to provide guidance to organisations setting up a patient involvement process.

In all good faith I downloaded the documents and began to read. Dull, dull, dull. I have completed the on-line survey but there is so much more to be said, so much that was missing.

 It should sparkle with ambition. It doesn’t. In my experience there is always a danger of a standards process becoming pedestrian. This one is mechanistic and will create a bland environment where achieving the minimum standard is the highest ambition. It will open the way for tick-box micro-management of daily involvement activity and no-one will ever address the question “why are we doing this?”.

Patient and public involvement is about transformation. I know this is ambitious and hard to achieve but it can be done and standards, if we have to have them, must aim high.

Patient involvement demands Board level involvement, not disinterested oversight. Senior managers must identity involvement opportunities within their direct remit. If only junior managers are doing it PPI will wither and fail. Senior managers should be asking every day “where can I involve a patient/public member” not “why should I involve…”

How can we attract high achievers as PPI managers? Absolutely critical for the future.

How do we position taking the role of a PPI manager as a ‘must do’ role for future chief executives?

As I know very well involved lay people can be great at finding gaps which surprise the professionals and open them up. Working together transformation becomes possible. You cannot train for this. You have to find the right people and create or manoeuvre the situations where they can do it. These people can be inspired by the opportunity, they won’t be inspired by a tick-box life.

I welcome standards if they help widen involvement opportunities and create structures that enable and encourage beneficial change. This exercise, as it stands at the moment, is about the detail of daily transactions, not about transformation. It will drive patient involvement into the side-lines.

NIHR – please start again.

Consultation web-page

The Standards survey

Precision medicine – promotion is an ethical challenge

Precision medicine is the carefully chosen term for what has been called ‘personalised medicine’. It is more appropriate but it still hides a range of issues affecting cancer patients which the promoters are not keen to discuss. When my eye was caught by the headline Cancer Care is Rapidly Changing — Here’s How You Can Keep Up it was no surprise to find precision medicine over promoted as usual.

The story describes the launch this week of Precision Medicine for Me which claims to take a new slant on the subject. It is a collaboration of more than a dozen patient organizations, patient advocates, startups, and industry leaders with the admirable objective to inspire and help patients understand and navigate the potential of new tumor testing, and raise awareness of the latest treatments and trials.

They discuss the challenge of getting tumours tested for genetic mutations, the fact that few centres which treat cancer have the capability yet, and the fact that it is costly. They skate around the fact that drugs may not be available to treat mutations which have been identified, drugs which might work may not be approved or funded for certain cancers, and that clinical trials of unproven treatments may be the only route open to a patient. It is a US initiative and the collaborators have a cancer background. One patient is named who has benefited from the approach.

Precision medicine is an important development, however it has a long term view even though it may benefit a select (and growing) group of patients in the meantime. Precision Medicine for Me is focussed on lung cancer, five of the collaborators are lung cancer specific. It is a matter of great regret that their story failed to focus on that specific point and made a promise to all cancer patients which cannot be met.

To illustrate the issues it may be useful to recall that one specific sarcoma benefited from one of the very first ‘precision’ drugs. Imatinib for GIST was first studied back in 2000 and was the fastest drug to achieve a licence when it was approved in the US and Europe. The rise of secondary mutations resistant to imatinib, commonly after about two years, has been followed by further drugs to treat them, or some of them. We now have strategies designed to delay resistance to imatinib. Mutation analysis has identified more than 40 secondary mutations. We have many patients alive after well over a decade of treatment, and all that is truly welcome. We also have patients who have died because the secondary mutations they faced are untreatable. Hopes we might have had for rapid development of similar treatments for other sarcomas have been dashed long ago.

This is a tough reality.

The truth is that at present more cancer mutations are being found each year than there are drugs to treat them. The FDA in 2016 licensed treatments for 11 cancer indications – 2 were extensions of an existing licensed drug, 2 were for side-effects – a total of 7 new cancer therapies (by the way one was for sarcoma). EMA’s activity was similar. This is a recipe for frustration – science can find the mutations but drug development cannot deliver the treatments anywhere near fast enough.

So beware promoting precision medicine. The danger of raising expectations in people desperate for treatment makes it unjustifiable. The ethics of unbalanced promotion are questionable, the science should be discussed but even the vaguest promises should be avoided. Ideally only specific clinical situations should be reported. The GIST story should be remembered and if it is replicated in other tumours it should be openly talked about.

Drug Cap has critical research implications

The announcement of NHS England’s £20m cap on costs of new drugs is the strongest signal yet that directions in cancer research need to change. Whether other countries will make similar decisions is hard to know, none have such centralisation as we have with the NHS.

Why, I hear you ask, does cancer research need to change direction?

Research is dominated by the pharmaceutical industry in its ceaseless search for new agents which can be patented and whose revenues will then fund the next generation of drugs. They also fund our pension schemes, we must not forget that. Socially we have a dichotomous relationship with them, we want their profits but we recognise that we are funding them. This hidden agenda has been present throughout the increasingly tense relationship between pharma and its demand for higher and higher prices, and healthcare systems which somehow or another have to be funded by consumers.

Now NHS England is calling a halt.

The £20m cap means a drug which costs £5,000 for a treatment will only get funding for 4,000 treatments. A course of eight treatments means that only 500 patients can get funded. This might work with a rare condition, it won’t where there are high volumes of patients. The signal to pharma is ‘drop your prices’. It is quite unequivocal. There will, of course, be plenty of occasions when the value of a drug is perceived to be so high that the cost beyond £20m will be carried; even so ‘drop your price’ will still be the message.

Research now has to focus on ‘value’, not clinical benefit. Pharma-led research has been driven by outcomes such as Overall Survival, and various surrogates for it like Progression Free Survival. Patients will tell you that survival with heavy side-effects is not necessarily good value. Spending all the time gained from treatment taking yet more pills, travelling to and from hospital or confined to home is not good quality of life. It is that quality which needs measurement and independent reporting. At the end of the day only patients can tell the regulators what represents good value.

There is another impact on research. There is now a real need for academic researchers to push pharma to look again at drugs which have not entered standard clinical practice. A drug which failed against the Overall Survival outcome for one cancer may have real value in another cancer. A drug licensed for one condition may have value in another for which it is not explicitly licensed. The value for pharma could be an extended exclusive patent period.

There are also drugs available to generic manufacturers, who are familiar with small scale proof of equivalence studies but rarely undertake exploratory studies. There should be the opportunity for academic researchers to work with them to open up new treatment opportunities, perhaps in rarer conditions where there are indications a drug might add value. A core issue here is preserving some income exclusivity for a company or companies which invest in this way. This is a regulatory challenge.

There is a huge resource out there which is largely unexploited. The £20m cap is a strong signal that we must start thinking outside the box

 

Research and advanced sarcoma

The research results reported at ASCO for sarcoma are of special interest this year because of the rise of immunotherapy as a cancer treatment. The expectation is that because sarcomas rely on gene mutations which the immune system fails to recognise it would, like other cancers, respond to immunotherapy. The treatment relies on two approaches, stimulating the immune system to overcome cancer’s ability to evade recognition and to block the ability which tumour cells have to hide from the immune response. This combination of approaches works well with melanoma, although the side effects are challenging and can require in-patient treatment.

Yes, it has been tried with sarcomas, albeit so far in small exploratory studies. The problem is that these explorations are not showing that any benefit results. It is very early days and we must hope that more extensive studies will deliver positive results. Researchers are optimistic but I have been around long enough to be cautious.

All kinds of treatments have been trialled to treat advanced sarcoma. A few individual patients have benefitted each time, I am one of them, but no drug treatment has come through to show the degree of patient benefit that would allow it to replace doxorubicin as the first chemotherapy of choice, the worldwide clinical standard.

Having all our eggs in one basket is not a strategy anyone wants to subscribe to. So research with other approaches to treating advanced sarcoma continues. It is an impressive list:

  • Molecular alterations to doxorubicin to improve its effectiveness and remove side effects
  • Innovative cytotoxic treatments using natural toxins
  • Better understanding of sarcoma mutations with the aim of matching existing or innovative new drugs to treat them
  • Exploring new drugs prospectively based on tumour characteristics, often through so-called basket studies
  • Exploring combinations of treatments which individually don’t quite make it, combining them with doxorubicin or with new drugs
  • Looking for a maintenance therapy which may prevent metastases
  • Developing new non-invasive techniques for removing lung metastases (eg RFA, SABR)
  • Understanding the value of surgery, especially with new techniques such as laser knife
  • Looking at the quality of life for patients with advanced disease, especially when further ‘curative’ treatment would be futile

Some of these approaches are showing positive results. It is increasingly important for clinicians to know the histological sub-type of sarcoma and to have genetic information. Alternative first-line treatment is currently for a small minority so it means that foreseeably patients with advanced sarcoma will continue to face the future with uncertainty.

Only a minority of sarcoma patients develop metastatic disease. Some will have recurrences which are local in their nature and although it is not nice to have to undergo further treatment they can be curable. There is hope the longer you can stay alive, so if the disease starts progressing taking every valid opportunity that arises is a realistic strategy. Our oncologists will be as encouraging as they can be within the bounds of realism when metastases appear. However where choices are offered there is little evidence which will definitively support one treatment approach over any other, although where surgery for metastases is offered my advice is to take it. Surgery is only a valid approach for a small proportion of patients, those with so-called oligometastases.

The annual ASCO event brings together specialists from across the globe, no other cancer event is comparable. Sarcoma is no exception to the rule. While it is exciting to see the range of research which is being undertaken to improve matters for patients it is a sad fact that in bone and soft tissue sarcoma we have not yet seen the kinds of breakthrough that have taken place in breast cancer, leukaemia, kidney cancer or more recently in melanoma. There is the example of GIST, a sensation at ASCO 15 years ago. It shows that it can be done in sarcoma, so there is hope, our specialist scientists and clinical researchers believe it can be done, we have to support and encourage them.

 

 

Chemotherapy 60 Years On 

It’s the 60th anniversary of the first use of chemotherapy. This is not an anniversary that is likely to attract much attention. It can be a demanding treatment and it does not get a good press. However we should not forget that it has saved lives and extended life for millions. We must also recognise that for some cancer patients it has failed to deliver any benefit.

It was in 1956 that a very rare cancer, choriocarcinoma – a cancer which starts in the womb – was treated with a drug called methotrexate. This drug, along with others, is still used for this cancer.

Today the most widely used chemotherapy worldwide is doxorubicin, the ‘red one’ that many patients will report. It was developed from soil based microbes, originally in Italy. It is used to treat a wide range of cancers and is regarded by the World Health Organisation as an essential ingredient in the drug formulary of every nation.  One major side effect of doxorubicin is that it can damage the heart. As a result the lifetime dose is limited. Today there are over 2000 variants.

The chemotherapy I had in 2000 was ifosfamide. This is also on the WHO list. It has its origin in nitrogen mustard – the main active ingredient in mustard gas. A drug derived from mustard gas was used in treating cancer as early as 1942 in the USA but it was too toxic and today is classified as a chemical weapon. Ifosfamide finally came into use in the early 1960s and today there are many variants. Its main side effect is haemorrhagic cystitis, a very unpleasant urinary tract complaint that can be fatal. A preventative drug called mesna is always prescribed alongside it.

Drugs based on platinum, taxanes derived from the yew tree and more recently drugs derived from toxins found in primitive sea creatures are also mainstays of chemotherapy. Treatment is often given with combinations of drugs and great care is taken to ensure that combinations do not have additive side effects which are hard to tolerate.

These cytotoxic treatments are being complemented today by hormonal and targeted therapies aimed at stopping specific genetic markers in tumours from being activated rather than at destroying tumours by blunt force. The ‘hammer’ of chemo is being replaced by subtler methods which are less toxic and more easily tolerated. I am told that there will be a place for chemotherapy for many years to come in treating cancer but the numbers of people needing these toxic treatments will slowly decrease.

Those of us who have been successfully treated with chemotherapy look back on the experience with no great wish to repeat it but we can at least celebrate the 60th birthday and give thanks for those scientists and researchers who have opened the way to life.