There is nothing more frustration that the current methods used by the FDA to approve drugs. The theory is great, but how it gets translated into our real world is killer, I mean a literal killer of men. The FDA wants assurances that before they approve a drug that it really works, or shows efficacy. This certainly sounds reasonable, but the method of evaluating efficacy is survival.

So, all the prostate cancer clinical trials require men to die. Fortunately, (but one could also argue unfortunately) men with prostate cancer often take many years to die, so we are forced to wait around year after year to count our brothers as they die. It is only after many years do we achieve enough deaths to be able to say that this drug gives a longer survival time over another drug or a placebo. In the mean time, we wait and not only do the men in the trial die, but all the rest of us not in the trial also die without access to this potential new treatment.

We are in desperate need to find alternative endpoints to death (or survivability). We need to find surrogate endpoints that reliably allow us to assume the survivability numbers without having to wait years and years of men dying.

There was just a paper published in Lancet Oncology, which is assessing the possibility of using circulating tumor cell (CTC) counts as a prognostic factor for survival (or as a surrogate endpoint). Dr. Scher from Sloane Kettering Hospital and his colleagues are currently involved in a trial with men who have progressive, metastatic, castration-resistant prostate cancer. They have been isolating CTC from blood samples at baseline and after chemotherapy treatment. Baseline variables, including CTC count, PSA level, concentration of lactate dehydrogenase (LDH), and post-treatment variables (change in CTCs and PSA) were tested for association with survival.

They have reported the following observations:

1- The variables associated with high risk of death were high LDH concentration (hazard ratio 6.44), high CTC count (hazard ratio 1.58), high PSA level (hazard ratio 1.26), low albumin (hazard ratio 0.10), and low haemoglobin (hazard ratio 0.72) at baseline.
2- At 4, 8, and 12 weeks after treatment, changes in CTC counts were strongly associated with risk, whereas changes in PSA level were weakly or not associated (p > 0.04).
3- The most predictive factors for survival were LDH concentration and CTC counts (concordance probability estimate 0.72—0.75).

They feel these results mean that the CTC count, analyzed as a continuous variable, might be used in the future to monitor disease progression and also as an intermediate surrogate endpoint of survival time in future clinical trials.

The Lancet Oncology, Early Online Publication, 11 February 2009
doi:10.1016/S1470-2045(08)70340-1Cite or Link Using DOI
Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial data

Joel T Nowak MA, MSW