Gynecologic Oncology Group (GOG) Clinical Trial

The Gynecologic Oncology Group (GOG) has decided to move forward with a study in platinum-resistant ovarian cancer, utilizing the Oncotech "EDR" assay to direct chemotherapy. The design is one that is bound to fail.

This assay is specifically designed to identify "inactive" drugs and Oncotech reports even state that the assay results should "not" be used to identify "active" drugs. A prior paper by Oncotech already established that the EDR assay can only identify a small percentage of patients who will "not respond" but then when the results were used to select an non-EDR alternative, it did not provide responses. In this light, the EDR assay has the advantage of telling you who will "not respond" but cannot in any way change the negative outcome by selecting an "active" alternative.

A pilot study, in which two GOG investigators used the Oncotech EDR assay to identify the "best" treatment regimens for platinum-resistant ovarian cancer was negative, with both assay directed and non-assay directed patients having the same median survival.

Proposals for a head to head comparison of the Oncotech EDR assay with the DISC (cell death assay) and the ATP (another cell death) assay have been submitted to GOG since 1992. They have refused to do the study and have, in the ensuing 13 years, received copious financial support from Oncotech, which seems to be the only relevant criterion motivating the GOG to perform clinical trials of assay-directed therapy.

I believe that a separate study, a front-line randomized trial with the primary endpoint being "time to disease progression," secondary endpoint being "overal, long-term survival," and third endpoint being "correlation between assay-directed and physician's choice therapy, would be more in keeping with positive results.

Assays based on "cell-death" occur in the entire population of tumor cells, as opposed to only in a small fraction of the tumor cells occurring in "cell-growth." Cell-death assays (DISC, MTT, ATP and Caspase 3/7) correlate very well with each other on direct comparisions of different methods.

Different methods of Chemotherapy Sensitivity and Resistance Assays (CSRA) results should be applied in choosing a particular drug regimen to be used in treating an individual patient's cancer. CSRAs will sort the different reasonable treatment regimens into the different groups (above-average, avereage, below-average and very below-average), which would direct attention away from regimens "less" likely to provide benefit and toward regimens which are "more" likely to provide benefit.

I am increasingly convinced, along with many others, that the best trial is a first-line study, no prior therapy, assay versus a control. However, the same people who maintain that assay directed therapy should not be used until "proven" in prospective randomized trials are the same people who control the clinical trials system, the grant review study sections, and the journal editorial boards, and these people have, through the years, refused, denied, and rejected any and all efforts made to get these trials off the ground.

All the while, at the same time vigorously defending a system in which chemotherapy gets selected more on the basis of remuneration and convenience to the oncologist than on the basis of the biology of the cancer.