New cytotoxic agents for prostate cancer on the horizon

Chicago-Although chemotherapy reigns supreme as the most effective systemic therapy to treat advanced prostate cancer, it is being contested with the rapid emergence and development of novel agents that are showing great promise in targeting pathways of cancer without causing damage to normal cells. However, it doesn't appear that chemotherapy will be relegated to the history books any time soon. Even if targeted therapies prove to be all they promise they may be, chemotherapy may still be essential.

"Many targeted agents may be added to or be synergistic with chemotherapy," said Robert Dreicer, MD, chairman of the department of solid tumor oncology at the Cleveland Clinic. "Therefore, chemotherapy will likely continue to be an important part of our therapeutic armamentarium."

Investigation into new cytotoxic drugs is therefore still ongoing. During the Perspectives in Prostate Cancer conference held here, Dr. Dreicer described some of the most promising of these drugs currently under investigation.

The epothilones initially carried a lot of momentum, according to Michael A. Carducci, MD, associate professor of oncology and urology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins School of Medicine, Baltimore.

"But as we look at the phase II data and try to plan phase III trial design, the momentum has sort of fallen off for those drugs," he said. "There is still some uncertainty as to where they would fit in or be different from what we already have."

Platinum agent shows promise

Satraplatin, a novel third-generation platinum agent, may be one of the most promising of the newer cytotoxic agents for the management of prostate cancer, according to Dr. Dreicer. A phase III, multinational trial evaluating the safety and efficacy of satraplatin plus prednisone (Deltasone, Meticorten, Orasone, et al) versus prednisone alone as second-line treatment in more than 900 patients with hormone-refractory metastatic prostate cancer completed accrual about a year ago.

"If this trial is positive, it is conceivable that the drug will be approved as second-line treatment for patients having received one prior chemotherapy regimen," he said.

A press release posted recently on the web site of GPC Biotech, which is co-developing satraplatin with Spectrum Pharmaceuticals, reported a statistically significant progressive-free survival with satraplatin in the second-line setting. Progression-free survival at the median (50% percentile) demonstrated a 13% improvement in patients who received satraplatin plus prednisone (11 weeks) compared with patients who received prednisone plus placebo (9.7 weeks), according to the release.

Although the study reached statistical significance in favor of satraplatin, the clinical importance of this finding for a patient remains unknown.

Both Dr. Dreicer and Dr. Carducci predicted that the future of cytotoxic agents will probably be as combination therapy with targeted therapies.

"I suspect we've pushed as far as we can with the cytotoxic agents in prostate cancer," said Dr. Dreicer, and he suggested that the emphasis of future research will likely be on targeted therapies.

Dr. Dreicer serves on the speakers bureau and receives research support from sanofi aventis; serves on the speakers bureau and as a consultant to Berlex Inc.; receives research support from Celgene and Eli Lilly & Co.; and is a consultant to Bristol Myers Squibb, Pfizer, and MedImmune.