Assay-Directed Clinical Trial

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A prospective, randomized clinical trial of physician's choice chemotherapy versus ATP assay-directed chemotherapy in non-surgically debulked, platinum-resistant ovarian cancer was presented by Ian Cree, M.D., Ph.D., Director, Translational Oncology Research Centre, Portsmouth, England at the May, 2005 ASCO meeting in Orlando, Florida. The results were highly suggestive of an effect due to the assay, and the most successful drug regimens used were nearly all developed using the assay. UK results in cancer are always lower than in the US for a variety of reasons. Part of this is probably lead time bias, but data on surgical debulking may be part of the explanation. Patients in the US get a whole lot more surgery along the way than in Germany and England, and it's not sure that it's our chemo which is doing the job or our surgery.

An abstract on chemosensitivity testing from the American Society of Clinical Oncologists Annual Conference in 1998, summarized a paper from a National Cancer Institute study which looked at thirteen different studies that searched into "in vitro" drug sensitivity testing for patients with cancer. It was noted that there were many different cancers represented in these studies, however, it was seen that the chemotherapy response rates went up using "in vitro" testing, as compared to using standard procedures, and patient survival increased using "in vitro" testing, as compared to using standard procedures.

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As a result of the Cree clinical trial, the Gynecologic Oncology Group (GOG) has decided to move forward with a study in platinum-resistant ovarian cancer, utilizing a different assay called EDR, to direct chemotherapy. However, this assay is specifically designed to identify 'inactive' rather than 'active' drugs. 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. At least it's a start!

There are other medical oncologists in the US, headed up by Drs. Larry Weisenthal and Robert Nagourney, that are making proposals for a separate study, a front-line randomized trial with head to head comparison of several assays (EDR, ATP, DISC, MTT, as well as Caspase 3/7). These assays correlate very well with each other on direct comparisons of different methods. Different methods of assay results should be applied in choosing a particular drug regimen to be used in treating an individual patient's cancer.

My question: Why did it have to take so long? Perhaps asking Schrag, Burstein, Von Hoff and the rest of ASCO, why they have single-handedly done more over the past 20 years to keep assay-testing technology under a bushel basket and out of the light until now? It has ultimately hurt literally hundreds of thousands of patients. We'd be much further along and technology would have improved, even more accurate. New treatments would have been discovered and targeted immediately to the people who could most benefit from them. This has been one great lost of opportunity in clinical cancer research, and that's what it is.