We have no idea, prior to treatment, whether a specific individual with hormone-refractory prostate cancer (HRPC) will respond to chemotherapy with docetaxel (Taxotere) — the only form of chemotherapy proven to extend survival of prostate cancer patients in randomized, Phase III clinical trials. However, we do now have some data suggesting that we may be able to predict length of overall survival (OS) 12 weeks after docetaxel treatment.
Hanninen et al. wanted to know whether docetaxel patients who had a rapid rate of PSA decline might experience a longer OS than those who had a slower rate of PSA decline. They investigated this by measuring what they called the PSA half-life (PSAHL), which was defined as the time to decrease of a patient’s PSA level from the baseline PSA at the time of initiation of treatment to 50 percent of that baseline level.
They reviewed the charts of 154 patients treated with docetaxel for metastatic HRPC in Alberta, Canada, between January 2000 and May 2006. They then determined the patients’ PSA responses and PSAHLs after 2 cycles of chemotherapy (i.e., at 42 days or 6 weeks) and after 4 cycles of chemotherapy (i.e., at 84 days or 12 weeks). Clearly, PSAHL values could only be determined in patients with a PSA drop from baseline.
Hanninen and his colleagues calculated that a PSAHL of 70 days represented a good “cut point” at which PSAHL might be used to impact OS.
Their results showed the following:
- At 42 days from the start of treatment there was no association between PSAHL and OS.
- At 84 days from the start of treatment, patients stratified by PSAHL demonstrated a significant difference in OS (15 months vs. 25 months) and this relationship remained following multivariate analysis.
- A more rapid rate of PSA decline (a PSAHL < 70 days) measured after 4 cycles of chemotherapy was associated with a longer OS.
- This result was independent of other known markers of survival and allowed for a greater survival differentiation than PSA response.
The ability to predict a good response to docetaxel chemotherapy is valaubale because it also impacts what other forms of management can be considered as most appropriate for the patients. It appears from this study that we may be able to get a strong indicator of potential survival using PSAHL.
It would be interesting to know whether this predictive method can be validated in a prospective clinical trial, such as the upcoming Phase III trial of Taxotere with or without OGX-011.
Filed under: Management, Treatment | Tagged: docetaxel, prognosis, PSA "half-life", survival
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Good study! Part of what I’ve found the most perplexing and frustrating in my going-on-4-year dealings with advanced prostate cancer is the uncertainty of it all. Any time anyone pins down some aspect of it, they’ve won my admiration and thanks. Thanks also to the men who participated in this study. Your contribution is much appreciated, and will not be forgotten.
I have a Gleason 9 T3cN0Mx diagnosis. I had four treatments of Taxotere (one every 3 weeks) immediately after conventional RP (positive margins, seminal vesicle involvement — lymph nodes removed but clean). My PSA decreased from 0.2 to 0.1 ng/ml after the first treatment and 20 months later is at 0.05 ng/ml.
Are there any studies on Taxotere and hormone-responsive patients?
Dear Mr. Stein:
I am not personally aware of any prognostic data similar to that in the study above that could be applied to hormone-sensitive patients.
However, I can say that if your PSA has remained stable for approximately 20 months since your initial treatment, you have a strong chance that it may remain stable for an extended period of time. Of course whether this is a consequence of the surgery or of the chemotherapy or the combination is probably difficult to ascertain with any degree of certainty.
From this study and others, may I conclude that, considering a Gleason 9, RP with positive margins and lymph node involvement, subsequent 70 Gy of radiation treatment and LHRH Trelstar-LA (thus far for 6 treatments of an 8-treatment scenario) and with current PSA that seems to be stable at 0.02 ng/ml — if my PSA goes up and I need docetaxel treatment, my OS will be estimated at 15 to 25 months after beginning chemotherapy?
Dear Mr. Helms:
No. It would not be accurate to think that your survival after starting chemotherapy would be limited in this way.
In the first place, the 15 months and the 25 months mentioned in the study were “averages” for all the men with PSAHLs of above and below 70 days. You could easily do better (or perhaps not so well).
So … in the second place — such averages do not apply to individuals. Your personal response to chemotherapy (should you need it) will likely depend on (a) your personal PSAHL from the time you start docetaxel: (b) just how much your PSA drops from its level when you start docetaxel treatment; and (c) how long your PSA remains stable at or near the nadir (lowest) level it reaches.
Furthermore, with new drugs coming to market and entering Phase III trials all the time, it is more than possible that we will have better options for someone whose PSA starts to rise on first-line hormone therapy soon — so docetaxel chemotherapy may soon become a much later stage option than it is at present.