Recent preliminary results from a Phase II clinical trial showed patients with recurrent glioblastoma multiforme, a form of primary brain cancer, experienced a significant tumor response rate with minimal side effects when treated with enzastaurin, an oral, targeted agent under development at Eli Lilly and Company.

On Thursday Eli Lilly & Co announced that it has stopped the Phase III trial of this experimental brain cancer drug. They determined that the treatment would not be any more effective than current chemotherapy treatments. The company said that it will still be evaluating enzastaurin as a potential treatment for non-Hodgkin's lymphoma. They will also be doing some trials that test the drug on other cancers, such as breast, colon, lung, ovarian and prostate.

Enzastaurin belongs to the families of drugs called protein kinase inhibitors and angiogenesis inhibitors.

The results of a Phase III clinical trial, published in the Journal of Clinical Oncology, concluded that Taxotere (docetaxel) plus Cytoxan (cyclophosphamide) resulted in better cancer free survival than the treatment combination of Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide).

Adriamycin and Cytoxan, referred to as the AC chemotherapy regime, has been the gold standard for adjuvant therapy for those patients diagnosed with early stage breast cancer. This study was conducted on more than 1000 women who had Stage I to Stage III disease. Half of the women were given the AC regime and the other half given the Taxotere/Cytoxan (TC) regime.

The results of the study showed that cancer free survival was 86 percent for those treated with TC an 80 percent among women treated with AC. Overall survival was 90 percent among women treated with TC and 87 percent among women treated with AC. Nausea and vomiting were more common among women treated with AC. Muscle and joint pain, edema, and low white blood cell counts accompanied by fever were more common among patients treated with TC.

After a patient receives a bone marrow transplant they are watched very closely for signs of graft-versus-host disease (GVHD).

When a patient receives a transplant of say a heart or liver, that patient is given drugs so that the body will not reject the organs. Your body does not recognize the organs as a part of you and the immune system will attack.

With GVHD it is the same concept but with a bone marrow transplant you are getting someone else's immune system. This foreign immune system does not recognize your organs and can then attack them. GVHD can affect different parts of the body such as the skin, eyes, stomach and intestines. GVHD can sometimes be easily treated and controlled or other times can be deadly.

GVHD can be acute or chronic. It is considered acute if it occurs within the first 100 days after the transplant and chronic if it persists or develops after day 100.

This study focuses on chronic GVHD and looks to determine the natural history of the disease and assess biological factors that may predict outcomes.

At times clinical trials are stopped because one arm of the study was doing so well on the trial drug that they wanted to put everyone on it. This of course definitely seems the right thing to do. What does that do to the trial then? Is there more that could be learned if the trial continued but in a different way?

Right now most drug trials use the frequentist statistical method to design and monitor a clinical trial. Apparently there is another statistical method that can do what the frequentist method cannot. The Bayesian method allows learning from the evidence as it accumulates. This means that when the trial is ongoing and something is learned it can be implemented into the trial for better results.

It seems that the Bayesian method is a bit more complicated to implement but this might be a step in the right direction for the future of clinical trials.

The UK Times Online ran a story about six healthy young male volunteers, who were to be paid £2,000 to participate in a clinical trial, suffering life-threatening side effects within minutes of receiving an experimental drug called TGN1412, which was being tested as a potential treatment for leukemia, rheumatoid arthritis and multiple sclerosis. At the time of publication, two of the young men given the drug remain in a coma at London's Northwick Park hospital. The other four had regained consciousness.

What makes this story alarming is the drug used in this trial was known to be highly toxic as a result of early trials of a similar drug, and the researchers launched a new study without consulting anyone who might have advised them against attempting the trial. In the news article, Angus Dalgleish, a world expert on immunology, is quoted as saying he was surprised the trial had been allowed to proceed given the outcome of earlier trials. In addition, Dalgleish brought into question the way the drug was administered at the start of the study. “I am amazed they gave it to six people at once instead of waiting to observe the effects in one of them.” Of course, there are two sides to every story, and this is only one set of facts. However, six young men, otherwise healthy at the beginning of this trial, were made quite ill. It's a cautionary tale.