Doctors argue over use of placebos in cancer trials

[Cary]

http://tinyurl.com/38bky

Doctors argue over use of placebos in cancer trials

By AMY DOCKSER MARCUS

The Associated Press

6/8/04 9:15 AM

The Wall Street Journal

In a controversial shift, some of the most promising new cancer drugs are heading into clinical trials where only some patients will get the actual drug. Other patients will be given a placebo.

The use of placebos is a sharp departure from past practices and is strongly opposed by some influential cancer researchers. Placebo trials generally haven't been used in life-threatening diseases such as cancer. If there is any kind of effective therapy available, the argument goes, it is unethical to give a placebo.

Now, drug makers including Bayer Pharmaceuticals Corp., Pfizer Inc. and Genentech are adding placebo arms to their trials in an effort to speed promising new drugs to market. Because placebo trials make it easier to verify results, the strategy can cut down on the need for additional studies and lead to faster regulatory approval.

Many in the cancer community are angry about the new approach, saying that it denies desperately ill people a last best hope. Some leading cancer centers, including the M.D. Anderson Cancer Center in Houston and the University of Michigan Cancer Center in Ann Arbor, have refused to put patients in clinical trials that use placebos. Patient-advocacy groups have met with drug makers including Pfizer and Bayer in an effort to change their minds about running trials with placebo arms.

Some of the most high-profile new drugs used placebo arms in recent trials, including OSI Pharmaceuticals, Genentech and Roche Group's Tarceva for lung cancer and Bayer and Onyx Pharmaceuticals Inc.'s BAY 43-9006 for kidney cancer. A Pfizer drug being tested for gastrointestinal stromal tumor (GIST) also has run a recent trial with a placebo arm. At the American Society of Clinical Oncology meeting this weekend, researchers presented positive results from the Tarceva and BAY 43-9006 trials.

The practice of using placebos in a study -- whereby some patients get the active drug, but others are given look-alike sugar pills and no treatment -- is the gold standard for drug research in many fields of medicine. The strategy makes it much easier to determine whether it is the drug, and not some other factor, that is making the difference in patients.

The U.S. Food and Drug Administration, responding to patients' concerns, has developed accelerated approval processes to speed drugs to needy patients even without placebo-based trials. Richard Pazdur, director of the FDA's oncology-drug products, says "we have not insisted that trials be placebo controlled." Drug companies say that such accelerated approval still requires certain additional trials that add to what already is an estimated $800 million price tag to bring a drug to market. And the research still takes longer to accomplish.

In addition to patients' meetings with Pfizer and Bayer in the past few months, other efforts are under way by patient advocates to influence trial design. A GIST patient-advocate organization, the Life Raft Group, has set up a Clinical Trials Advisory Group of cancer patients to lobby drug companies against placebo trials. In November, three major professional organizations of cancer clinicians, oncologists and researchers will meet to come up with better ways to design trials for the new therapies that are emerging.

All this comes amid growing concern that it is getting harder to get patients to participate in cancer-drug studies in the first place. Just 3 percent of adult cancer patients enroll in clinical trials, according to the President's Cancer Panel report issued last week. A number of national organizations, including the National Cancer Institute, the Lance Armstrong Foundation and the National Coalition for Cancer Survivorship, all are trying to increase the percentage of adult cancer patients who enroll in trials.

What all these groups have found is that one reason patients don't enroll is fear of getting a placebo, so the outcome of this current debate is sure to affect recruitment efforts. The University of Michigan Cancer Center in Ann Arbor, along with the M.D. Anderson Cancer Center in Houston, both refused to participate in Pfizer's clinical trial for GIST patients because of their concerns over the trial's placebo arm. "There is almost no good reason to ever do a placebo trial in cancer," says Laurence Baker, director of clinical research at the University of Michigan center. "The only advantage is expediency to the drug manufacturer."

When OSI Pharmaceuticals ran recent Phase III clinical trials for its drug Tarceva, for advanced lung cancer, the company didn't include any U.S. sites, concluding "it would take too long to enroll patients" because of the trial's placebo arm, according to OSI Pharmaceuticals Chief Executive Colin Goddard. This meant that patients here lost early access to a potentially beneficial drug. The company reported this weekend at ASCO that the drug extended the lives of patients who took it.

Mr. Goddard acknowledged that patients on placebo died more quickly than those with the drug. But that "thanks to the sacrifice of those patients, we've taken lung-cancer treatment forward," Mr. Goddard said. "Future patients will benefit."

Some drug companies say they are working to come up with innovative trial designs. In the current Phase III trials for Pfizer's GIST drug, called SU-11,258, doctors are allowed to intervene if a patient's tumor grows more than 20 percent. If it turns out the patient wasn't receiving the active drug, the patient is allowed to "cross over" to the drug arm and begin receiving the medicine. "We tried to minimize the number of people getting a placebo," says Charles Baum, the global clinical leader for the drug at Pfizer.

Bernie Kaplan, 64, who was diagnosed with GIST in 2000 is enrolled in the Pfizer trial. When the first assessment showed that his tumors had grown, "I was praying I was on placebo," he says. It turned out he had been given a sugar pill. When he started receiving the drug, his tumors shrank.

Many pharmaceutical companies say the very nature of these new cancer drugs makes it imperative to have a placebo arm for comparison. Unlike traditional chemotherapy, which is designed to shrink or eradicate tumors, many of these drugs aim to stop or slow tumors' growth and allow someone to live with their cancer. This makes it harder to measure if it is the drug that is working, or whether someone simply has a less-aggressive tumor. In addition, some of the diseases these drugs are targeted at have no other therapy against which a new drug can be compared.

Bayer, which is testing its BAY 43-9006 in kidney-cancer patients, adopted a placebo-trial design in its Phase III trial of the drug that began in October 2003. This weekend, the company reported extremely promising results with an earlier-phase trial of the drug -- 37 out of 106 kidney-cancer patients had their tumors shrink 25 percent or more, and 38 had stable disease.

Early positive results such as this make patient-advocate groups even angrier that some patients in later trials won't get any drug, effectively meaning they will die. A group of patients met with Bayer in December to discuss the trial design but, says patient advocate Steve Dunn, "they wouldn't budge."

Susan L. Kelley, Bayer's vice president for product development in oncology, says pharmaceutical companies are trying to do the right thing. She says there are no options for kidney-cancer patients against which to compare the new drug. And, Dr. Kelley says, the company cannot allow patients on placebo whose tumors grow to then receive the drug, because "it would confound our ability to follow survival. We need definitive evidence that the drug is active."

[Ry]

Hey good for the University of Michigan. Cary I like your new picture.

Rochelle

[Elaine]

This article blew my mind. I feel a rant coming on, but I best think on it for a bit. I hope all of us take the time to read the article and maybe as a group we can do something like prepare a position statement on this to send to the proper government agencies and our representatives as well as to other funding organizations.

This is an important topic/discussion. Thanks, Cary for finding and posting this.

elaine

[Addie]

Much as this whole article made me sort of shiver uncomfortably.....when I got to this:

Susan L. Kelley, Bayer's vice president for product development in oncology, says pharmaceutical companies are trying to do the right thing. She says there are no options for kidney-cancer patients against which to compare the new drug. And, Dr. Kelley says, the company cannot allow patients on placebo whose tumors grow to then receive the drug, because "it would confound our ability to follow survival. We need definitive evidence that the drug is active."

....I about blew a gasket. God forbid that anyone with a spreading cancer should "confound (their) ability to follow survival"....when, in fact, those on the placebo may NOT survive!

I wonder how Bayer would feel if this study were done ONLY on relatives of Bayer employees? Would THAT make a difference in terms of their apparent INDIFFERENCE about who survives or who messes up their ability to track survival?

They need "definitive evidence" while the cancer patient has needs that are, apparently, not as important as the drug company's, I guess.

D*mn......I gotta reread and think about this some more, but this irks me. This irks me a lot that the lives of desperate people matter less to some of these drug companies than their blinkin' statistics or capacity for making as much money as possible.

And while I'm at it...in a related irritation....some newsman was interviewing a mucky muck with the drug co. that makes Iressa yesterday....making comparisons with Tarceva and whether or not Tarceva will eventually cut into Iressa's market. I got so angry, as the questions the news guy was asking ALL sort of related to finance and profits....and NOT to the fact that both these drugs may extend or save lives.

I mean, let's talk about what really matters here, buddy...and it AIN'T some pharmaceutical company's profits. It's the potential for prolonging or saving lives!!!!!!!!!

Sheesh....some people just don't get it, do they?

[Hebbie]

I am dumbstruck. I don't know whether I am about to bust a blood vessel from anger, or burst into tears of frustration.

Mr. Goddard acknowledged that patients on placebo died more quickly than those with the drug. But that "thanks to the sacrifice of those patients, we've taken lung-cancer treatment forward," Mr. Goddard said. "Future patients will benefit."

I am absolutely sickened at this information. Peoples LIVES are on the line and they give them SUGAR PILLS? (a cancer feeder according to certain theories) and commend them for their "sacrifice"?

And they wonder why only 3% of cancer patients enroll in trials?

I also have to ponder the fact that MANY individuals here have bent over backwards trying to qualify for trials and due to the many particular qualifications, they can't get in.

We are doing everything possible to find and enroll in trials -- they are just to specific to let in the masses.......

This really burns me up.

[Cary]

I could hardly believe this article when I first read it also. I did go back and read Hebbie's recent post "Treatments boost lung cancer survival" and apparently we all missed the hints at the end of the article.

“Not only did our patients live longer but I like to say they lived better,” she said, noting that patients given the drug had less cough, shortness of breath and pain than those given placebo.

Erlotinib, co-developed by OSI Pharmaceuticals, Roche and Genentech, works by inhibiting an enzyme called epidermal growth factor receptor, or EGFR, that is involved in the growth of some cancers.

In the study of 731 patients, those receiving erlotinib survived a median of 6.7 months, compared with 4.7 months for those on placebo. After one year, 31 percent of those in the treatment group were alive, compared with 22 percent of the other group.

Cary

PS: Ry, I also have great respect for the University of Michigan and Dr. George Brewer, without them my dad wouldn't be here today.

[cathy]

I am sitting here shaking my head in disbelief..I remember reading someones post a while back, that they were entering a clinical trial and there was a chance they would receive a placebo, I thought back then that I was just not understanding the post right because giving a placebo to a cancer patient would be inhumane, but it looks like I did understand it correctly, thats just crazy..

Thanks Cary for the information, I like the picture too...

[Hebbie]

I REALLY thought the protocol with trials was that if you didn't receive the trial drug you received the "best standard care" -- i.e. an approved chemo drug.

What the %*#(@%!??????????????

[Snowflake]

When I was offered Iressa, it was as a double-blind study. I told my oncologist I wasn't interested in being treated as if I WAS taking a medication to keep it from coming back if I was truly doing nothing (and note, if you are in ONE trial and POSSIBLY on the placebo, you are NOT eligible to sign up for another one). After that discussion, he found a study that was just the effects of the drug and put me on that - short-lived victory, he pulled me from the study two months later due to "effects"! (Hey, I was ready, believe me....)

Thanks, Cary, for the article. I found it to be disheartening and cold toward any "poor sucker" that signed up for their trials...

Becky

[Cary]

I always believed the same as Hebbie, that the patient would always receive the "best standard care" apparently I was wrong. As disheartening as this article may seem, there will always be ethical/humane researchers and institutions that will not follow this new "trend" (hopefully).

Cary