The Medical Innovation Bill

What happens when you reach the end of the road with the standard cancer protocols? A patient starts with first-line treatments, usually a combination of chemotherapy, surgery and radiotherapy, depending on diagnosis and disease staging. If the response to that first-line isn’t positive, the disease continues to spread, then there’s a second-line and possibly a third-line treatment, depending on the type of cancer and how the patient responds to these often toxic treatments. And if the disease is still there at the end of this gruelling process? At this point the prognosis is pretty grim. What happens then?

At this point I should say that I’m speaking from direct personal experience with my son, George, who died almost three years ago from metastatic osteosarcoma that resisted every treatment thrown at it. And from the experience gained in the years following his death in trying to help other people in a similar situation, often also suffering from Li Fraumeni Syndrome as George did.

What happens? In the first instance the lead oncologist will often look for a clinical trial, hopefully a Phase II or Phase III trial. But often the patient will have already been on a trial and come out the other side with the disease still active. In practice if there are trials available, and often they are not, it will be a Phase I trial. The aim of a Phase I trial is to find the right dose to use in a Phase II trial, which is looking to see how well a drug works. Efficacy – how well the drug works – isn’t normally the primary outcome from a Phase I trial.

And if there’s no trial, or you don’t want to go on a Phase I trial with a new drug that might have toxic side effects and no effect on your disease? Then you are in the realm of palliative care. If there’s no standard treatment and there’s trial, then the emphasis is on trying to keep a lid on the symptoms and trying to preserve what quality of life you have given the advanced state of the disease.

But what if there’s something that doctors are using in another country? What if there’s a drug that has been shown to have some effect in your type of disease? What if there are other options that aren’t covered by the standard protocols?

Curcumin - Bioavailability Results

I have written before about curcumin, the yellow pigment from the spice turmeric, and its anti-cancer properties. In the lab there is ample evidence from petri dishes and test tubes, and evidence too from animal experiments aplenty. It seems to act in multiple ways across a wide range of different cancer cell types. On paper at least, it's one of the most promising of the food-derived agents and there are lots of people who are convinced that by itself it can act to protect from the toxicity of chemotherapy and radiotherapy, to act directly against the inflammation implicated in cancer-initiation and as a drug to kill established tumours. The reality is somewhat less impressive than all of the lab work suggests and the clinical trials to prove one way or another are mostly still in progress or not on the drawing board.

One trial that is in progress I have written about previously (www.anticancer.org.uk/2011/12/curcumin-trial-in-uk.html). It's a UK trial looking at curcumin combined with standard chemotherapy for inoperable colorectal cancer. The same team behind the trial have published some interesting results on one of the main issues in the use of curcumin as an anti-cancer drug: bioavailability. Like many other polyphenols with anti-cancer properties, such as resveratrol or quercetin, curcumin suffers fom low levels of bioavailabilty. This means that to get a therapeutic level a person has to take an awful lot of the stuff, and even then it's often doubtful how much gets through digestion and metabolism and into the tissues to do any good. In this trial patients took 5 × 470 mg (2.35 g total) tablets of Curcumin C3 complex for two weeks. This is a relatively low dose compared to some trials where patients took 6 g or even 12 g a day - that's a lot of tablets to take - and the question was whether this dose would even be detectable or not.

The first thing to report is that few patients (six of 24) reported side effects, and these were mild tummy upset, in contrast to studies with higher doses. In this trial only one patient out of 24 reported unpleasant side effects after two weeks of curcumin. The suggests that a good dose for future trials is between 2 and 3 g of curcumin a day. Blood tests revealed that curcumin was detectable in nine of 24 plasma samples, all 24 urine samples, and in the colonic mucosa of all 23 biopsied participants. High levels of topical curcumin persisted in the mucosa for up to 40 hours post-administration.

At the same time this trial asked patients about what they felt about taking curcumin as a treatment. Sixteen participants (67%) stated that they would take curcumin long-term should it be of proven benefit, providing further support for future trials.

While this is a long way from showing that there is a direct clinical benefit from taking curcumin, it's another small step in the right direction. The trial has established a dose that gives detectable levels of curcumin and its metabolites in the colon and has shown that there's some support from patients - with the important proviso that it's shown to be beneficial. And for that we still have to wait.

The results are published as open access here: http://cancerpreventionresearch.aacrjournals.org/content/6/2/119.long