The most important thing to know about Phase II trials is that while they are intended to determine whether a treatment is effective against cancer, they cannot determine whether the new treatment is any better than the standard treatment. Moreover, there's no assurance that the treatment will work at all; fewer than half the treatments tested in Phase II end up being tested in Phase III. On top of that, even if the new treatment does turn out to show some effect, it may be no better--and it may even be worse--than standard treatments.

And just because a treatment has passed its Phase I toxicity testing, there's no assurance that it's completely safe. To begin with, as all people with cancer are certainly aware, most cancer treatments are inherently toxic. And remember that Phase I studies involve only a small number of patients. If a certain side effect occurs in only one in a hundred patients, it may well be noticed first in a larger Phase II trial.

On the other hand, some people regard Phase II trials as the best avenue for cancer patients considering a clinical trial. Lydia Cunningham Rising, a Detroit-based patient advocate who has advised more than 500 cancer patients on clinical trials, gives the following advice:

If you qualify for more than one clinical trial, all things being equal, I would take the Phase II. Phase I is obviously more experimental. It's a toxicity trial, so there's a greater chance for adverse side effects, and less of a chance of a therapeutic effect. And when you go into a Phase III trial you have the chance of being randomized.

Joe was basically told to go home and get his affairs in order, but he is alive and well today--fourteen years later--due to an experimental treatment he received 2,000 miles away from home.

But then, just four months later and after a course of radiation therapy, Joe's cancer returned. Desperate to find some other avenue to a cure, Lydia began researching the medical literature. She learned that chemotherapy for brain cancers is often ineffective because of the blood-brain barrier, a protective mechanism found in the brain's blood vessels that keeps out most foreign substances. In addition to protecting the brain from bacteria, viruses, and poisons, the blood-brain barrier unfortunately also prevents many healing medications from getting through. But Lydia also learned about Dr. Edward Neuwelt of the Oregon Health Science University, who was experimenting with a technique called barrier disruption.

Dr. Neuwelt found a way to temporarily break down the blood-brain barrier, allowing chemotherapy to reach the tumor. His studies had just reached Phase II, and Joe enrolled in the trial.

My husband was the tenth person in the world to have this treatment. Within a month after treatments started 90 percent of the tumor was gone, and by the end of the year there was no trace of it.

Phase II trials typically enroll fifty to one hundred patients, and in most--but not all--Phase II cancer trials there's no randomization. Moreover patients are generally given a more thorough course of therapy than in Phase I.

However, the requirements for entering a Phase II trial are often very strict, since, for statistical rigor, the investigators want to test the treatment on a homogeneous group of patients with well-defined disease.

One of the criteria for most Phase II trials, in contrast to both Phase I and Phase III, is that patients must have measurable disease. As Steve Dunn explains it,

In Phase II trials the objective is to see what percentage of people have their tumors shrink and go away, and how long they stay away. It turns out that in order to do that you need a tumor you can measure the size of. That way, when it gets smaller you can tell.

If you're a patient with kidney cancer and you had a recurrence only in your bones, you might not be able to get into a Phase II trial. If it has spread to the lungs, though, and there are these measurable nodules, then you probably could get into a Phase II trial.

Advantages of Phase II trials

• As in Phase I, it's a chance to receive a treatment that may be better than anything else out there years before it hits the market.

• Treatments in Phase II trials have passed Phase I toxicity testing, and the maximally tolerated dose has already been determined. This generally means that you'll be given the highest dose that had acceptable toxicity.

• Phase II cancer trials are usually not randomized.

• Phase II trials tend to last longer than Phase I trials, increasing the likelihood that you'll experience a therapeutic effect.

• Even if the treatment does not work for you personally, you may take comfort in knowing that your participation in the trial will help other cancer patients down the road, and it will also help the advancement of medical science.

Disadvantages of Phase II trials

• The treatment may be ineffective against your cancer, or it may be no more effective than standard treatments.

• Even though the treatment has passed Phase I toxicity testing, you may experience unexpected or serious side effects, including those that can lead to permanent damage.

• The inclusion and exclusion criteria are usually very strict.

• You will generally be eligible for Phase II trials only if you have measurable disease.

• A Phase II trial tends to last longer than a Phase I trial. It will likely require more clinic visits and a greater time commitment.

• Since Phase II trials are sometimes not multicenter trials, you may have to travel long distances for treatment.

Notes

1. Lydia Cunningham Rising described Joe's odyssey in personal interviews with the author and in a magazine article (Lydia O. Cunningham, "I Promise I'll Get You Well," Woman's Day, October 21, 1986). A newspaper article describing the science behind and the promise of barrier disruption by focusing on Joe Cunningham's experience in Dr. Edward Neuwelt's clinical trial appeared in the Los Angeles Times: Thomas H. Maugh II, "New Tumor Treatment: Breaking the Brain Barrier," Los Angeles Times, September 21, 1987.