1. What proof would a new gold standard be to Mary X and Sandy Y? Is Mary X part of the average in the clinical trial? Or is Sandy Y part of the average in the clinical trial? In other words, if it would help Mary X, whould it help Sandy Y?

At present, clinical trials are highly empirical, they test drugs on general populations and then look for a clincial response and a treatment effect that is not likely to be a chance result. However, the side effect of this is inflexibility, some patients may unnecessarily be exposed to inferior experimental therapies.

A problem with the empirical approach is it yields information about how large populations are likely to respond to a treatment. Doctors don't treat populations, they treat individual patients. Because of this, doctors give treatments knowing full well that only a certain percentage of patients will receive a benefit from any given medicine. The empirical approach doesn't tell doctors how to personalize their care to individual patients.

The number of possible treatment options supported by completed randomized clinical trials becomes increasingly vague for guiding physicians. Even the National Cancer Institute's December 7, 2006 official cancer information website states that no data support the superiority of more than 20 different regimens in the case of metastatic breast cancer, a disease in which probably more clinical trials have been done than any other type of cancer.

More clinical trials have not produced more clear-cut guidance, but more confusion in this situation. It is more difficult to carry out clinical trials in early stage breast cancer, because larger numbers of patients are needed, as well as longer follow-up periods. But it is likely that more trials would lead to the identification of more equivalent chemotherapy choices for the average patient in early stage breast cancer and in virtually all forms of cancer as well.

So, it would appear that published reports of clinical trials provide precious little in the way of "gold standard" guidance. Almost any combination therapy is acceptable in the treatment of cancer these days. Physicians are confronted on nearly a daily basis by decisions that have not been addressed by randomized clinical trial evaluation.

Posted at 7:34PM on Dec 7th 2006 by Gregory D. Pawelski

2. It would seem to me that more should be done in identifying those at risk for recurrence in early stage breast cancer, and the trials at this point in time, should pertain specifically to subgroups.

Posted at 2:01PM on Dec 8th 2006 by Dr. Al Wilke

3. I couldn't agree more about identifying those at risk for recurrence in early stage breast cancer. For the vast majority of cancer patients, the cancer will not recur regardless of whether they receive chemotherapy. There is a good portion of cancer patients that are either undertreated or overtreated because there was no adequate information on who will recur. The Oncotype DX (and there are others) is another test to enhance the ability to distinguish between low risk and high risk patients. Patients in the high-risk group, who would benefit from chemotherapy can then be pre-tested to see what treatments have the best opportunity of being successful, and offers a better chance of tumor response resulting in progression-free survival, while those in the lower-risk groups can be spared the unnecessary toxicity, particularly associated with ineffective treatment.

Improving cancer patient diagnosis and treatment through a combination of cellular and gene-based testing will offer predictive insight into the nature of an individual's particular cancer and enable oncologists to prescribe treatment more in keeping with the heterogeneity of the disease. The biologies are very different and the response to given drugs is very different.

Posted at 10:09PM on Dec 8th 2006 by Gregory D. Pawelski