Searching for Clinical Trials

Looking for a clinical trial can be a daunting experience. It may be that you are doing this just to see what's out there, but it's more likely to be that you - or a friend or family member - have just had some bad news about treatment and you need to review options. At times like this you may not know where to turn. The aim of this article is to offer some guidance in what is likely to be a difficult time.

The first and most important thing to keep in mind is that clinical trials are conducted for different reasons - and this is normally indicated by the phase of the trial. The most important of these are Phase I, II and III trials.

Phase I trials are normally the first trials of candidate drugs or other treatments in humans. To get to Phase I a drug will have gone through 'pre-clinical' testing in the test tube (in vitro) or in animals (in vivo). Occasionally a drug might be tested in tiny amounts in humans before going into a proper Phase I trial. The key aim of the Phase I trial is to find the appropriate dosing of the drug. The effectiveness of a treatment is of secondary importance. The researchers are convinced by the pre-clinical evidence that the drug has some effect, but they need to establish a proper dosing schedule before they can focus on how good it is in practice. This is an important point to keep in mind. Also, Phase I trials tend to be on a small in scale (there are only a few patients, often based at a single hospital or clinic and with small research team).

Phase II trials take things a step further. At this point the drug or treatment has been through Phase I. The dose has been established and there are often some indications of effectiveness. There's still an element of looking at the dosing schedule or treatment protocol, but the emphasis is now on seeing whether the positive effects seen in the pre-clinical studies actually hold true in humans. Phase II studies are often larger in scale - more patients, more doctors, possible multiple locations.

Lines of Communication

An interesting little story caught my eye on one of the science web sites this week. It‘s a report of a recent study that found that ‘managing communication around cancer diagnosis gives patients sense of control in an otherwise uncontrollable situation’. The researchers found that:

...communication is an important factor in coping with cancer in that it enables people to exert control during a highly stressful and turbulent time. However, despite best efforts to structure and control that communication, cancer patients cannot always predict or control other people's reaction.

In our experience the need to communicate with friends and family simply became exhausting. Particularly when you’ve just had bad news, the need to relay it multiple times just makes you feel worse. The constant repetition of bad news is depressing, especially when you know that the person on the other end is going to react badly to it too. It means that not only do you have to deal with your own reactions, but you end up having to manage other people’s too. It increases the stress precisely when you’re most stressed out.

George's 18th Birthday

Today should have been George's 18th birthday. Instead it's just a little over three months since his death, on April 25th 2011. We miss him always but today it hurts so much more because we know how much it would have meant to him. He should have had a whole life to look forward to...

Although we are consoled by the knowledge that he knew how much we loved him, and that he loved us in return, the injustice of it all is still hard to deal with.The world moves on, but for us, the world is a poorer place without him.

Meeting your oncologist

Most of the articles on this site have so far focused on cancer research or the politics of that research. However, the intention is to do more than just summarise results or to argue for changes in policies, it is also firmly about providing practical support and advice to cancer patients, their families and friends. With that in mind this post is going to look at something that might seem trivial but in reality is absolutely essential – how to approach the meetings with your oncologist or other specialist. While some people will view an article like this as being a bit pointless, there are others who might gain some useful tips, particularly as we all have a tendency to defer to our doctors. The whole area of doctor-patient relationship is a bit of a nightmare, for all sides, but unless that relationship is solid things will be more difficult than they should be.

When you first get your diagnosis, or when waiting for results from scans or examinations, you will be stressed on meeting your doctors. No matter how much you like them or respect them, you’ll be feeling tense and nervous, a not a little apprehensive. Sitting in the waiting room can be hard, especially if the clinic is running late and you’ve been waiting for ages (which was the norm, in our experience). At times like these it’s easy to get so stressed that you forget to ask the things you’ve been meaning to ask. It’s ridiculous, because you may have been waiting for ages to ask these questions, but you can be blindsided by news (good or bad), get diverted by some other train of thought or simply forget everything and just sit there passively while the doctor leads the discussion. Afterwards, you’ll kick yourself for not having remembered to ask your questions and will either have to wait for the next appointment or get on the phone or look for someone else to ask.

Curcumin and the Drugs Industry

Looking through some of the previous articles on this site you’ll notice frequent mentions of curcumin. Of the many food-based anti-cancer agents, this extract from turmeric (the yellow spice used in curry), is one that generates a lot of scientific interest. Curcumin has anti-oxidant, anti-inflammatory and a wide range of anti-cancer properties. It is cheap, non-toxic and has been used as a traditional medicine for hundreds of years. In terms of research, it has plenty of in vitro and in vivo evidence against a wide range of different cancers. What’s more, there have been early stage clinical trials that show that even at high doses curcumin is non-toxic. There are lots of positives about curcumin, but there are also some significant issues. First and most obvious is that it suffers from very low levels of bioavailability. In other words it takes a lot of curcumin to generate even low levels in the blood stream. Secondly, most of the in vitro and in vivo studies use the raw material, but when we take it orally it gets metabolised as we digest it, so it’s not pure curcumin that circulates in the body (though in the digestive tract things are different, obviously). These issues are not unique to curcumin by a long shot, and they are discussed in more detail in the articles on How To Read A Cancer Paper (here and here).

Even with those caveats, curcumin is an interesting substance that bears closer investigation. But, given the urgency with which we want the research to proceed, you have to ask yourself why such a positive drug candidate has not moved further. Where are the large scale trials in cancer patients? Why isn’t curcumin part of the everyday armoury that we use against cancer?

Q&A with Dr Gerald Krystal - Low carbs and cancer

Following my recent article on a recent paper that looked at the effect that a low carb diet had on slowing tumour growth (and if you haven’t read it, I suggest you do that before reading the rest of this…), I contacted one of the authors, Dr Gerald Krystal of the University of British Columbia with a list of questions. Dr Krystal has kindly responded with some more information, which I think is useful for those people considering starting a low carb diet in line with the results of his team’s work.

PP: The low carb diet includes foods high in amylose. Doesn't this make it difficult to translate into a diet people can follow? Are there foods that are naturally high in amylose?

GK: There are many foods that are naturally high in amylose. For example, all legumes (beans, lentils and peas), basmati rice, new potatoes, bananas, whole grains, sweet potatoes, radishes and parsnips. Try and avoid regular "old" potatoes, white rice and white bread (whole wheat bread is not much better….bread with whole grains is the best when it comes to breads but I try and avoid all breads. If you can't resist, sourdough is not bad because of its low pH…if you add a tsp of lemon juice or vinegar to any meal you can lower the glycemic index by about 1/3). Another interesting tip is if you let cooked rice cool it becomes more resistant to digestion so eating sushi is better than eating hot cooked white rice. I would love to see a breakdown of digestible carbs into % amylose and % amylopectin down the road on food products. Also, there are ongoing studies in the US to generate genetically modified potatoes (lacking 2 enzymes that are used to put the branched sugars on the glucose polymer to convert it from a linear glucose polymer (amylose) to a branched glucose polymer (amylopectin, which is more easily broken down). Don't know how you feel about genetically modified foods but this could dramatically lower blood glucose spikes after eating potatoes.

PP: Why is it that so much mainstream dietary advice for cancer patients seems so unhealthy? Why are patients still being encouraged to have high calorie diets?

GK: This drives me crazy as well. The main concern of cancer clinicians today is cachexia (wasting). I understand this is something you want to avoid but I think that lowering our carb and raising our protein intake will have a substantial benefit, especially for early pre-metastatic cancers. In keeping with this I would like to see clinicians substitute amino acid/PBS intravenous drips for the currently used 5% dextrose (glucose) PBS to rehydrate cancer patients.

Low carb diets and cancer

The Warburg Effect

It is well known that a hall-mark of cancer cells is an increase in the use of glucose – the so-called glycolytic switch is an early indicator of malignancy (a change that is a part of the Warburg effect – which is worth following up if you're interested). This greediness for glucose is exploited in PET scanning, where radioactively tagged glucose is injected into the patient and, several hours later, a scan is taken to track where the radioactivity has accumulated in the body. Tumours absorb much higher amounts of this radioactive glucose than the normal tissues, and show up as 'hot spot' on the scans.

Tackling this greediness for glucose underlies a number of different approaches to attacking cancer, and one obvious avenue for this is to look at diet. Before we get into this, however, it's worth pointing out that many mainstream oncologists and dieticians are incredibly blasé about this topic. From our experiences in many different hospitals and with different doctors, we know that the mainstream advice for cancer patients is not to change the diet in any major way. Time and again we were told that keeping the calorie intake high and maintaining weight were the most important considerations. Any questions about limiting carbohydrate intake to starve tumours were simply dismissed as untested and unproven hypotheses and therefore best avoided.

That said, there have been numerous studies that have looked at the influence of diet on cancer growth. Many of these have been rodent studies, but there have also been some patient studies performed, mostly these have looked at brain tumours (glioblastoma). Furthermore, much of this research has involved a ketogenic diet, which is a high-fat and extremely low-carb diet, which has been used clinically in the treatment of epilepsy. In terms of being able to follow this yourself, it's no easy task, this is an extreme diet, much more extreme than the strictest Atkins diet for example.