Sunday, April 08, 2007

New prostate treatment

Seattle-based biotech Dendreon is hoping to get U.S. approval for the first cancer drug that would train the body to fight off cancer on its own, with few side effects. But researchers, statisticians and Wall Street analysts are fiercely debating whether there is enough data about this radical new treatment.

Dendreon's Provenge is a so-called cancer vaccine. Researchers prefer the term immunotherapy because it would treat, not prevent, cancer. A personalized drug, composed of human immune system cells, is created for each patient; the idea is to give the immune system the tools it needs to fight off the disease.

On Thursday, a panel of experts convened by the Food and Drug Administration will debate whether the drug is ready to be marketed. The FDA often follows the recommendation of such panels, but it doesn't have to. Already, briefing documents have been posted saying that the drug seems very safe--although there is a worry of stroke--and reviewing the arguments about whether or not it is effective at prolonging patients' lives.

Why is there any question at all? When researchers run a clinical study, they define a specific goal. For instance, that drug will extend life over a prespecified time or prevent tumors from growing compared to a placebo. The whole study is designed around this goal. If the trial falls short, its results can only be used to generate new questions, not to draw scientific conclusions.

Provenge has failed in both of its main studies--but it seems to help patients live longer. The clinical trials tested the drug in a relatively small number of cases, with only 127 men in the main study who showed a benefit. But survival was extended four months for patients with metastatic prostate cancer. Statistical rules aside, Provenge fans say, survival is awfully hard to fake, and desperate metastatic prostate cancer patients who would get Provenge have only one drug, the chemotherapy Taxotere, at their disposal. The Taxotere drug, made by Sanofi-Aventis, has many unpleasant and dangerous side effects.

The data has convinced some who were skeptical that Provenge may have merit. Philip Kantoff, a urological oncologist at Harvard Medical School and the Dana Farber Cancer Institute, is conducting a big clinical trial that should firmly establish whether and how much Provenge helps patients. He has consulted with Dendreon. For a long time, he was one of Provenge's doubters. "I thought the concept was too simplistic for belief," Kantoff says. "I didn't think it had a snowball's chance in hell of working."

But the data showing the drug increases survival has made him cautiously optimistic. "I'm still skeptical, but I think there's something going on here," he says. His doubts rest mainly on the fact that results were small. "If this were a much larger study, to me this would be a slam dunk."

Kantoff says that if the drug were approved, he would probably prescribe it. So far Provenge seems mostly to cause flu-like symptoms, but FDA reviewers note there may also be an increased risk of stroke. If the medicine is fairly safe and might be effective, why not offer it to patients?

David Penson, a urologist at USC's Keck School of Medicine, has also gone from being a doubter to an investigator in a Provenge clinical trial and a consultant for Dendreon (he says he has received less than $10,000 in fees). "When they first released their data, they had to massage some data to show a clinical difference," he says. Dendreon's first study showed efficacy only in less-sick patients.

Colleagues convinced Penson to give Provenge a try in clinical trials, and he was impressed. He remembers one patient, a doctor, who went from being wasted and fatigued from his metastatic prostate cancer to being able to play golf again. Patients don't care if a drug meets the original primary endpoint of Dendreon's study, an improvement in X-rays, says Penson. "All they care about is living longer."

This is the argument at the heart of the case for Provenge. Neal Shore, medical director of the Carolina Research Center, says rejecting Provenge now would be "grossly unfair to the patients who have no other options but to enter clinical trials." Shore argues that "a lot of people will end up dying" before bigger clinical trials could show a benefit.

But there are other issues at play. Once a drug is approved, other medicines can get on the market by proving they are better. If an ineffective drug slips through, that could open the door to other less effective medicines. Another worry is that the benefit of Provenge might be real but less robust than it appears. Because larger issues are at play, this is exactly the kind of situation in which the FDA might go against the decision of an advisory panel. Even if Dendreon has a great day on Thursday, the company won't be home free.


Pesky! Top nutritious choice is in the can

CHALLENGING a long-held belief, a Choice study has found that canned and frozen vegetables can be more nutritious than their fresh counterparts. The consumer magazine tested frozen, canned, week-old and fresh vegetables, both cooked and uncooked, for the contents of certain nutrients. With the exception of broccoli, all canned and frozen vegetables tested contained more or equal percentages of vitamins and anti-oxidants.

"Frozen English spinach was more nutritious than cooked fresh spinach," Choice spokeswoman Indira Naidoo said. Canned tomatoes contained about five times more lycopine, which is believed to prevent heart diseases and prostate cancer, than fresh ones. Accordingly, canned green beans and carrots were more nutritious than their fresh counterparts, and there was little difference between canned and fresh corn.

The vegetables were purchased in Melbourne, but University of Queensland expert Mike Gidley said he would not expect different results for vegetables bought in a Queensland supermarket. "Absolutely fresh is the most nutritious," the director of Centre for Nutrition and Food Sciences said. "But what we call fresh has often taken a long time to get from the field to the supermarket."

New technologies made it possible to keep these vegetables looking fresh for weeks, Choice states. Frozen and canned vegetables, in contrast, are often processed directly after being picked. When buying canned vegetables, consumers may face another problem. Choice claims it is very difficult for Australian consumers "to compare the true cost of prices". Cans in different sizes have different prices, and sometimes bigger cans or packets are not the cheapest option as one might believe, Choice states.



Just some problems with the "Obesity" war:

1). It tries to impose behavior change on everybody -- when most of those targeted are not obese and hence have no reason to change their behaviour. It is a form of punishing the innocent and the guilty alike. (It is also typical of Leftist thinking: Scorning the individual and capable of dealing with large groups only).

2). The longevity research all leads to the conclusion that it is people of MIDDLING weight who live longest -- not slim people. So the "epidemic" of obesity is in fact largely an "epidemic" of living longer.

3). It is total calorie intake that makes you fat -- not where you get your calories. Policies that attack only the source of the calories (e.g. "junk food") without addressing total calorie intake are hence pissing into the wind. People involuntarily deprived of their preferred calorie intake from one source are highly likely to seek and find their calories elsewhere.

4). So-called junk food is perfectly nutritious. A big Mac meal comprises meat, bread, salad and potatoes -- which is a mainstream Western diet. If that is bad then we are all in big trouble.

5). Food warriors demonize salt and fat. But we need a daily salt intake to counter salt-loss through perspiration and the research shows that people on salt-restricted diets die SOONER. And Eskimos eat huge amounts of fat with no apparent ill-effects. And the average home-cooked roast dinner has LOTS of fat. Will we ban roast dinners?

6). The foods restricted are often no more calorific than those permitted -- such as milk and fruit-juice drinks.

7). Tendency to weight is mostly genetic and is therefore not readily susceptible to voluntary behaviour change.

8). And when are we going to ban cheese? Cheese is a concentrated calorie bomb and has lots of that wicked animal fat in it too. Wouldn't we all be better off without it? And what about butter and margarine? They are just about pure fat. Surely they should be treated as contraband in kids' lunchboxes! [/sarcasm].

Trans fats:

For one summary of the weak science behind the "trans-fat" hysteria, see here. Trans fats have only a temporary effect on blood chemistry and the evidence of lasting harm from them is dubious. By taking extreme groups in trans fats intake, some weak association with coronary heart disease has at times been shown in some sub-populations but extreme group studies are inherently at risk of confounding with other factors and are intrinsically of little interest to the average person.