Time for Change

There have been many incredible advances in the treatment of adult cancers in the past 10 years, but childhood cancer is losing out for many reasons, including the opportunity for industry to apply for waivers in the drug development process. Investigating new agents in children and adolescents is particularly difficult as their numbers are few, studies are costly and outcomes are not guaranteed. This leads to long delays for companies who answer to shareholders, and so sadly a waiver to avoid having to test efficacy in children is the attractive option for many. The bottom line is that children are often sidestepped in the drug development process because of financial challenges.

It is a well-known fact that most children diagnosed with cancer are treated with chemotherapy drugs which are over 30 years old. If we continue to do this, then current survival rates for the most resistant cancers are unlikely to change, the prospect for cure at relapse remains low, and the toxicities (both acute and long-term) will remain unchanged. By ignoring these issues, we are failing our children. Cancer is the number one cause for death by disease in children and adolescents, but in the adult world it is no longer recognised as the automatic death sentence that it once was. Childhood cancer is genetically a much simpler disease, with lower molecular mutation rates. Children and adolescents also have substantially less co-morbidities given that they have exposed their bodies to fewer toxins in their short lives. All these elements point towards the fact that childhood cancer should be addressed in a much more positive and productive way, which is likely to lead to much greater curative rates than are currently being achieved.

Developing new drugs specifically for children will address many of these issues, but another key element to consider is prioritisation. Although 35,000 children and adolescents are diagnosed with cancer each year in Europe, when this number is attributed to individual diseases and disease sub-categories, the numbers of children and young people in each classification are few. This makes prioritising drug development another key issue, as only the most promising compounds and technologies should be brought to the fore for testing when it comes to these very small populations. Children are precious, and should be treated as such in every regard, including childhood cancer research.

Many parents and charity advocates are extremely knowledgeable on this topic, and have spent years campaigning to bring these issues to light. Unite2Cure is uniting these highly informed people and groups to gather momentum to bring one voice to the European Commission in asking for change to regulation to address these core issues. We recognise that difficulties exist for other stakeholders, but we believe many of these can be overcome by making small but strategic changes to the European Paediatric Medicines Regulation.

Parents who have lost their children to cancer, parents who live in fear of relapse and nurse their children through long term side effects, and charities supporting these desperate families all recognise the need for change and see an opportunity for it to happen. Academics understand the limitations of the current regulation and research landscape. Paediatric oncologists state that they don’t want to be the generation who simply administered drugs to maintain this current curative plateau. Surely those highly skilled, highly paid individuals working within drug development grasp these issues and are keen to change the future of many children diagnosed with this devastating disease?

If only it was considered a good return on investment, then this might be the case.

Show your support by signing our petition.

Leona Knox, Unite2Cure

Making better use of known drugs in treating children with cancer

Given the mountain we still have to climb when it comes to treating childhood cancers, it seems wise to explore all possible paths to new treatments.

Drug development is notoriously risky and expensive. This creates a formidable barrier to the introduction of new medicines for children with cancer as the pharmaceutical industry prefers to invest in the development of drugs for the much larger adult cancer population, which holds the potential to repay for the heavy investment and risk. With very few exceptions, specific drugs for children with cancers are not developed and the only hope for sick children is that at some point some of these “adult” drugs will be tested and eventually used in children.

This is far from ideal as children and adolescents with cancer do not have the time to wait. New treatment options that are more effective and safer are urgently needed. While we at U2C are busy working on introducing more effective incentives for companies to develop new medicines for childhood cancer, there are some possible approaches that may bypass the above mentioned hurdle and may be championed by parents’ organisations.

These approaches include drug repurposing and metronomics.

Drug Repurposing, sometimes also called drug repositioning, is the re-use of an existing drug for a new disease. Very often a drug is developed to treat one illness and it is later discovered that it can treat another as well. In the case of cancer, there is evidence that a range of non-cancer drugs may also have anti-cancer effects which may be clinically useful. These drugs, many of them commonly available as generics, are cheap and have low toxicity as well as decades of clinical use for their original uses. While there is a range of evidence to support the anticancer effects of these non-cancer drugs, including some antibiotics and antifungals, there is a need to develop and run clinical trials to put the anticancer effects to the test in the same way as we do with other potential cancer drugs. However, because these drugs are generic there are no commercial incentives to run expensive clinical trials or to license the drugs for new uses if the trials succeed. Therefore, in addition to medical innovation there is also a need for financial innovation to overcome the regulatory barriers to change. Another potential advantage of this approach is that very often these repurposed drugs have been used already in children and adolescent for the treatment of other disease, therefore we would have confidence on the safety of these “old’ drugs in the treatment of children with cancer. This is not a trivial benefit in view of the well-established toxicity of currently used cytotoxic agents.

There are many examples of successful repurposing already. Methotrexate, one of the first drugs developed to treat childhood cancer, is now being used to treat arthritis. Propranolol, used to treat high blood pressure in adults, is now used to treat infantile hemangioma, a disfiguring and sometimes dangerous benign tumour in babies and toddlers. Thalidomide, a drug notorious for causing birth defects when used to treat morning sickness is now being used to treat leprosy and multiple myeloma. This is the only successful example of repurposing a non-cancer drug in oncology, but there is evidence that many more drugs have the potential to do the same.

Metronomics is another approach to drug development that has the potential to impact childhood cancers. Conventional chemotherapy remains the mainstay of treatment in both adult and childhood cancers. It is normally delivered at high doses and is associated with a range of side effects including hair loss, nausea and vomiting and neutropenia (increasing the risk of infection). However, many of these very toxic drugs also show signs of anticancer activity when used at very low doses. Using the drugs at these low doses means that the side effects are minimal and that there is no need for treatment breaks for the body to recover – mostly the drugs are given orally and every day (hence the term metronomic chemotherapy).

In contrast to high dose chemotherapy, metronomic chemotherapy does not cause neutropenia and in fact the evidence suggests that it can boost the anticancer activity of the immune system. The other main action of metronomic chemotherapy is to control the blood supply to the tumour, cutting off the nutrients and oxygen that tumours need to survive. While there have been many clinical trials of metronomic chemotherapy in a wide range of cancers, including some very hard to treat cancers, there is a need for large definitive trials in pediatric cancers. As with drug repurposing the challenges are not just medical but also financial as many of the drugs suitable for metronomics are old generic chemotherapy agents such as cyclophosphamide and methotrexate.

Drug re-purposing and metronomics are just two example of innovative approaches for the development of new treatments for children with cancer that hold the potential to deliver quicker benefit to patients. If you want to know more and hear about some examples of ongoing projects in the childhood cancer area please do not hesitate to contact us.

Cesare Spadoni
Pan Pantziarka




Ashburn TT., Thor KB. 2004. Drug repositioning: identifying and developing new uses for existing drugs. Nature reviews. Drug discovery 3:673–683.