We’re coming to the end of the era of clinical research on adjuvant cytotoxic chemotherapy of breast cancer. There now are numerous studies evaluating various regimens with anthracyclines and taxanes, and I don’t think there’s another cytotoxic agent out there that is likely to move the field strongly forward. From this point on, the adjuvant breast cancer trials are going to largely focus on the addition of biologics.

— Peter Ravdin, MD, PhD
Breast Cancer Update, Issue 1, 2006

It has now been five years since our CME group incorporated prostate cancer into our educational tent. Along the way, it has become increasingly apparent that the clinical research structure for this disease is woefully inadequate considering its enormous human impact. If you’re a man — hell, if you’re a woman — you should be incensed that more isn’t getting done.

The archaic nature of the available clinical research data for a disease that will be diagnosed in one of seven men who live to be age 80 is readily apparent everywhere we turn, particularly in adjuvant systemic therapy. God knows how many years ago, Bernie Fisher and the NSABP forced breast cancer clinicians and investigators to focus on research addressing adjuvant systemic therapy, as opposed to extensive local treatment, as a means to lower tumor-related mortality. As this strategy proved successful, research in other tumor types followed suit, leading to the following situations:

1. Breast cancer: As noted above by Adjuvant! wizard Peter Ravdin, we’ve pretty much moved beyond trials attempting to integrate novel chemotherapeutic agents.
2. Colon cancer: The NSABP recently completed accrual to a 2,600-patient trial (C-08) evaluating adjuvant chemotherapy with the anti-VEGF agent bevacizumab.
3. Lung cancer: Adjuvant chemotherapy is now of proven value, and trials are being launched to add biologics.
4. Prostate cancer: For some reason, no one got the message, and the one major US trial of adjuvant chemotherapy (SWOG-S9921) closed recently without meeting its accrual goal after more than six years of sluggish participation. Also, there is no randomized study confirming the role of androgen deprivation in the adjuvant setting or at PSA relapse, which is the current standard of care. That’s right, sports fans. No randomized data. Zero. Zip. Zilch.

What makes this even more troubling is that every day, patients with prostate cancer and PSA elevations are subjected to the painful rigors of life without testosterone, and we don’t have a shred of supporting level III evidence to justify it. As a mildly hopeful sign of better things to come, well-designed trials are now being launched to evaluate docetaxel in the adjuvant and PSA-only settings, but with an annual US mortality of approximately 30,000 men, and hundreds of thousands of others plagued by the morbidities of therapy, is that the best we can do?

The graveyard that is prostate cancer clinical research is profoundly offensive to my gender and, for that matter, to our society, but the more important question is, how do we get things on the right track? One striking difference between prostate cancer and the rest of cancer medicine is the relatively minor role medical oncologists play in managing this disease. Med oncs live and breathe clinical research, but currently, they usually become involved in prostate cancer management only when first-line systemic therapy is no longer working. Maybe if these docs jump in feet first, this mess will get cleaned up.

On a more global level, the key to pulling prostate cancer research out of the muddy ditch on the side of the road may be to somehow encourage the industry to become more involved. That’s right. The NCI, private foundations and nonprofits have taken their crack at this, and the result is an embarrassment. For all the complaining about the “exorbitant” costs of new systemic agents, I have a lot more confidence that capitalists can solve the problem rather than bean counters.

We need more people like Steve Shak to make things happen in prostate cancer. While working at Genentech, Steve played a central role in the development of trastuzumab (Herceptin^®) and now with his own company — Genomic Health — has changed the treatment plan for tens of thousands of breast cancer patients with his innovative Oncotype DX™ tissue assay that predicts the benefit of adjuvant chemotherapy in specific patient populations. It would also be helpful if more groups like the NSABP with their megabrained pathologist Soon Paik got involved in kick-starting an ailing prostate cancer clinical trials mechanism.

I recently ran into Sir Richard Peto and asked him what was happening with the publication of the international prostate cancer overview of adjuvant androgen ablation, which was first presented in a closed meeting several years ago. Peto shrugged and told me he had been tied up with a new breast cancer meta-analysis, which is at least 25 years ahead of prostate cancer in the questions being posed. As a privileged invited guest to that unique closed prostate meeting in 2002, I watched Peto and his team present their data in an ancient Oxford lecture hall with UCLA medical oncologist Rowan Chlebowski. We were both amazed at the lack of clinical trial evidence on toxic therapies being given to tens of thousands of men with the disease. Most of the prostate cancer combined trial analyses had fewer patients than many of the recent individual breast cancer trials of aromatase inhibitors.

For this issue of Patterns of Care, we include postsurvey comments from five medical oncologists regarding the major clinical scenarios that are contributing to prostate cancer mortality: intermediate- and high-risk localized tumors, PSA relapse and metastatic disease. Behind the suffering of men with these tumors and their loved ones is a sad and inescapable truth: Prostate cancer research has failed them miserably, and it will take a miracle to awaken this slumbering giant and get something done.

— Neil Love, MD
NLove@ResearchToPractice.com

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