Wednesday May 19 2010
The drug was given alongside radiation therapy
“Cancer patients may be offered new hope in the form of a harmless virus which can reverse even apparently untreatable forms of the disease,” The Daily Telegraph has claimed.
The study behind the claim was a very preliminary trial, which gave 23 people with advanced, treatment-resistant tumours a combination of radiotherapy and a new drug called RT3D. The combination produced few side effects and a few patients saw a small reduction in tumour size three months after treatment. However, this was a ‘phase I trial’, a type of very early study that is designed to establish the safety of a treatment ahead of larger studies looking at the drug’s effectiveness.
The drug pipeline can be a long one, and it starts with small studies such as this. More research, which may take years, will determine whether newspapers are correct in predicting that the drug might halt cancer.
Where did the story come from?
This study was carried out by researchers from The Institute of Cancer Research, The Royal Marsden Hospital NHS Foundation Trust, The University of Surrey, Leeds Institute of Molecular Medicine and other research centres in the US and Canada. No sources of funding were reported. The study was published in the peer-reviewed medical journal Clinical Cancer Research.
The newspapers have accurately reported the findings of this paper, but are premature in hailing this a ‘magic bullet’ that can “bring hope to thousands given no chance of survival” or cure untreatable cancer.
What kind of research was this?
This is a phase I trial involving 23 patients with a variety of advanced tumours for whom curative treatment was not available. They received radiotherapy, at various doses, in addition to variable doses of the experimental drug – reovirus type 3 (RT3D).
RT3D is a virus that naturally occurs in the respiratory and digestive systems of most humans without causing harm. It has been shown to activate anti-tumour immune responses. Previous studies suggest that injecting viruses that have similar anti-cancer properties into the body is quite safe, although their effectiveness at fighting cancer has not really been demonstrated.
This phase I study tested the effects of a combination of RT3D and palliative radiotherapy, a programme of radiotherapy designed to alleviate some of the symptoms of incurable cancer. As a phase I trial, the objective of this research was to see whether there was any negative interaction between the two, to explore its effects on the body and on the cancer and to establish a safe dose that could be used in future research trials. Phase I trials are very early stage clinical research trials that report on the experience of treating a small number of individuals. They are not intended to test how effective a new treatment is.
This was an open label trial (meaning that both patients and researchers know which treatment a patient has been given). It did not feature any comparator groups receiving other drugs or placebos.
What did the research involve?
The researchers enrolled 23 patients who had advanced cancer (of various tumour types) that was not responsive to standard cancer treatment, but who were suitable for palliative radiotherapy. People were excluded if they had previously received radiotherapy to the site to be treated, had cancer spread to the brain, were receiving immunosuppressive therapy or had received any other investigational therapy in the past month.
Patients were divided into groups of three, with each group prescribed a different dose of RT3D. The groups were further divided into low-radiation or high-radiation groups. Low-radiation groups received radiotherapy given on five consecutive days (a total of 20 grays of radiation across five sessions) plus two injections of their prescribed dose of RT3D, injected directly into the tumour on days two and four. The high-radiation group received a total radiotherapy dose of 36 grays in 12 sessions over 16 days. The patients also received either two, four or six doses of RT3D.
The main outcomes of interest were safety and adverse effects, replication of the virus in the body, immune response and anti-tumour effects.
What were the basic results?
Of the 23 patients, 18 completed the full treatment course. All treated patients tolerated RT3D at whichever dose they were given. The most common adverse effects were a low-grade fever, flu-like symptoms, vomiting and a drop in white blood cell count (although this was not associated with symptoms). Blood, urine, stool and sputum did not contain the virus, which indicates that it was not replicating. RT3D did not exacerbate any adverse effects of radiotherapy.
The researchers assessed how treatment affected tumour size in 14 patients over the next three months. In the low-dose radiation group, two of seven patients had a partial response (decrease in the size of the target tumour), and five had stable disease (no size change). In the high-dose radiation group, five of seven patients had partial response, and two had stable disease.
How did the researchers interpret the results?
The researchers conclude that the combination of RT3D and radiotherapy was well tolerated, and a ‘favorable toxicity profile’ and lack of viral replication suggests that this combination should be also be assessed in newly diagnosed patients who were receiving radiotherapy courses intended to cure their cancer.
This is a phase I trial of RT3D, used in conjunction with radiotherapy in 23 people with advanced, treatment-resistant tumours. Although the combination was well tolerated in all patients, the extent of tumour response was assessed in only 14 patients. Of these, only half of them had a partial response with a small reduction in tumour size by three months. This cannot be considered to be a ‘cancer cure’ in the terms used by the news headlines.
A phase I trial is an early stage of research. The treatment needs further testing, which will no doubt follow. Larger, more rigorous studies will determine which groups of people the drug is most suitable for; whether it is more effective than placebo treatment; whether it is more effective than alternative treatment or palliative options; and whether there are any potential safety concerns. The drug seems well tolerated in these few patients, but there may be common adverse effects or rarer serious adverse effects that become apparent over time or with wider use. Only larger studies can investigate this.
Dr Joanna Owens, science information manager at Cancer Research UK, highlights an important point, saying: “While these results are encouraging, it’s important to stress that this treatment has been tested in only a handful of patients so far.”
The early nature of this research does not yet support RT3D’s use as a treatment but it highlights it as a candidate for further research. This includes larger trials within palliative care programmes, and also in research involving people who have earlier stage disease, where RT3D is combined with programmes of radiotherapy designed to cure cancer.