Prostate Cancer Update 1

Tracks 1-11

Track 1	Introduction
Track 2	Clinical trials of docetaxel-based chemotherapy for advanced prostate cancer
Track 3	Clinical experience with docetaxel in prostate cancer
Track 4	Tolerability of docetaxel chemotherapy
Track 5	Use of chemotherapy for patients with PSA progression
Track 6	Patterns of medical oncology referral in prostate cancer treatment

Track 7	Efficacy of chemotherapy in the treatment of prostate cancer relative to other common solid tumors
Track 8	Future directions in prostate cancer clinical research
Track 9	Duration of endocrine therapy for patients with high-risk disease
Track 10	Clinical use of maximal androgen blockade
Track 11	Bicalutamide monotherapy

Select Excerpts from the Interview

Track 3

DR LOVE: Would you discuss your clinical experience with docetaxel for the treatment of prostate cancer?

DR FERRARI: It is quite extensive. We have been using docetaxel or taxane-based chemotherapies since the late 1990s. Overall, my experience with this agent has been extremely positive.

I have seen many patients who are highly symptomatic, either with bone pain or obstructive symptoms. Some of them come into the office in a wheelchair or are hardly able to walk, and over the course of two to three months, you see remarkable changes both in their symptoms and in their overall sense of well-being and quality of life.

At times, as oncologists, we may be reluctant to start treatments for these patients because they are impaired in terms of their quality of life or their ability to move around, and we believe that the weakness or fatigue associated with chemotherapy could worsen their quality of life. But, not surprisingly, because of the response rates that docetaxel elicits in the control of pain — not control of PSA progression — these patients’ conditions reverse remarkably.

I could provide you many anecdotal stories, but I think the most significant aspect has been the overall experience and what the major studies ultimately showed (Petrylak 2004; Tannack 2004; [1.2, page 6]). Furthermore, it’s not simply a PSA response or a 25 percent reduction in the size of the metastases; more than anything it’s an improvement in their quality of life and the ability in many cases to return to their normal activities.

Track 4

DR LOVE: What type of toxicity do you observe with docetaxel?

DR FERRARI: The side effects depend on the schedule you use. If we use the standard every three-week schedule — which is the schedule that has been approved by the FDA in combination with prednisone or estramustine — the higher doses cause hair loss. Generally it’s not full baldness, but hair thinning and partial hair loss definitely occur.

Another symptom that we see is fatigue. Generally, most men describe fatigue within 72 hours or so after treatment. If I treat someone on a Wednesday or a Thursday, he might feel a bit more fatigued on Saturday or Sunday but not sufficient for that to carry over so he would not be able to go to work on Monday.

Perhaps the most common side effect is neutropenia. A decrease in the white cell count generally tends to occur anywhere between seven and 10 days post-treatment.

Track 5

DR LOVE: Do you reserve chemotherapy for patients who have definite metastatic disease, or do you also offer it to a patient with PSA-only disease that has a rapid doubling time?

DR FERRARI: Although the docetaxel trials established the advantage of chemotherapy in men with definite metastatic disease, previous experience with other tumors tells us that an active combination of agents against androgen-independent cells is most likely to be effective earlier than later.

Prostate cancer is a heterogeneous disease. We will probably eliminate the tumor cells that are more sensitive early on, and cells that emerge subsequently or that survive this initial attack may be less sensitive to treatment.

All of the time that we gain is valuable, but I don’t necessarily wait for the development of metastases. If the patient failed second- or third-line hormonal therapy and his PSA continued to rise, I think it would be time to initiate chemotherapy, even if he might be asymptomatic, because you know where he’s heading. Once symptomatic metastatic prostate cancer is in place, it’s much harder to achieve control of symptoms and complications from the metastases.

Track 9

DR LOVE: Would you discuss the research data that have become available over the last couple of years examining various types of endocrine intervention?

DR FERRARI: The key trials that have been published are from the radiation therapy series and from the radical prostatectomy series. From the radiation therapy series, the milestone publication by Bolla (Bolla 1997) demonstrated that adjuvant hormonal therapy for three years in locally advanced prostate cancer offered a survival advantage (4.1, 4.2).

Subsequent studies that were conducted by the RTOG (Lawton 2001; Hanks 2003; [3.1, 3.2, pages 14-15) also showed that prolonged androgen suppression for two years offered a survival advantage and indicated a potential to cure a higher number of patients with high-risk localized disease. By now, the use of adjuvant hormonal therapy has widely become the standard of care for patients with high-risk features at presentation who have localized prostate cancer.

What is not yet completely defined is the duration of treatment. Certainly, the benefits of using adjuvant hormonal treatment for two and three years have been shown, but some data also show that six months of hormonal therapy may offer a benefit for patients with intermediate-risk disease (D’Amico 2004).

The risks of prolonged androgen deprivation for two and three years are not welcomed by anybody, and the chances of recovering potency and libido after two or three years of prolonged androgen suppression are extremely slim.

In the radical prostatectomy series of trials, the only data available are from the study by Messing (Messing 1999), showing that men with microscopic metastatic deposits in the lymph nodes at the time of radical prostatectomy who received hormonal therapy had improved overall survival compared to those who received no hormonal therapy.

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