Select Excerpts from the Interview
| Tracks 1- 4 |
| Track 1 |
Introduction |
| Track 2 |
Case discussion: A 46-year-old
man with PSA-only, hormone-refractory
disease |
|
| Track 3 |
Chemotherapy for PSA-only
disease |
| Track 4 |
Clinical use of intermittent
androgen therapy |
|
|
Tracks 2-3
DR LOVE: Would you present a patient from your practice who exemplifies
the challenges of using chemotherapy for prostate cancer?
DR PETRYLAK: Sure. This is a 46-year-old man who had a radical prostatectomy
four years ago with lymph node-positive Gleason 9 disease.
He underwent maximal androgen blockade, and approximately nine months ago, he started having a rising PSA level. We withdrew bicalutamide and started him on ketoconazole and cortisone, and he had a short response that lasted four or five months. Now his PSA level is rising again. In fact, it rapidly rose from about six or seven to 50 ng/mL in a four-week period and then to 70 ng/mL after another two weeks.
DR LOVE: Why did you decide to treat him initially with maximal androgen blockade?
DR PETRYLAK: In his situation, it was clearly supported by the Messing study, in which early hormone therapy was better than delayed hormone therapy. It came at the cost of losing his sexual function, but he wanted to live and he wanted to see his son grow up.
DR LOVE: How did he tolerate the androgen deprivation?
DR PETRYLAK: He tolerated it very well, with minimal hot flashes, and he gained only five pounds over the last couple of years.
DR LOVE: What convinces you that combined blockade is “state of the art”?
DR PETRYLAK: When you look at the meta-analysis, you see a small — approximately four percent — but detectable difference in survival in favor of combined blockade. Other therapeutic interventions have been done for similar benefit, and I believe it’s appropriate.
DR LOVE: So this patient was hormone refractory, although he still had PSA-only disease?
DR PETRYLAK: Correct. Based on this rapid PSA doubling, I was not comfortable
with just waiting and watching until he developed metastatic disease. So I started him on docetaxel, 75 mg/m2 every three weeks as a single agent. He has just completed his second cycle, so it’s too early to tell how well he will respond, but he is tolerating it very well.
DR LOVE: What are your thoughts about the use of chemotherapy for PSA-only disease?
DR PETRYLAK: We need to be selective. We don’t have trials to determine the best time to use chemotherapy.
An interesting study that has come out over the last several years was done by Matt Smith, in which he analyzed PSA doubling times and absolute PSA values in relationship to the development of bone metastases in asymptomatic
patients with a rising PSA. Only about a third of those patients eventually
— at least in the time frame he analyzed — developed metastatic disease (Smith 2005).
The most important prognostic factors for the development of metastatic disease were a PSA doubling time of less than 6.3 months and an absolute PSA value greater than 24 ng/mL (Smith 2005). But, again, we don’t know if those are the patients who would benefit from early therapy.
DR LOVE: Do we know anything about the impact of chemotherapy, specifically
docetaxel, in PSA-only disease?
DR PETRYLAK: We know we’ll see the PSA decline, but whether we can delay the development of bone metastases is unclear at this point.
DR LOVE: What do you say to your patients about what to expect in terms of the side effects and toxicity from docetaxel?
DR PETRYLAK: The major side effects are neutropenia, numbness in the fingers and toes, edema, lacrimation and fatigue. I tell patients that they may develop some of these side effects or no side effects whatsoever. We can also sequence their treatment such that their most difficult day as far as fatigue is concerned winds up on the weekend rather than during the week.
Track 4
DR LOVE: What do we know about the efficacy of intermittent androgen therapy?
DR PETRYLAK: Theoretically, it has good grounding. Some good preclinical work evaluated this in the Shionogi tumor model (Akakura 1993) and in the LNCaP (Sato 1996; Hobisch 2004; Eggener 2006). We will need to see the clinical data, but it will be interesting to see the results from the SWOG trial of intermittent therapy (SWOG-S9346; [3.1, 3.2]).
If intermittent therapy is inferior to combined androgen blockade administered continuously, questions will be raised as to whether the experimental
arm used in the SWOG study is as good as some of the other types of intermittent therapy used in the community. We’re all awaiting the results of that
trial because it will make a major impact on patient care.
DR LOVE: Is that a strategy you use in your practice off protocol?
DR PETRYLAK: Yes. I tell patients up front, “I still believe the standard of care
is combined blockade administered continuously; however, if for any reason
you can’t tolerate the treatment, it’s acceptable to receive it intermittently.”
Select publications
