PSADT value limited in predicting cancer outcome

September 1, 2006

Atlanta-PSA doubling time (PSADT) appears to have limitations as a predictor of treatment outcome, according to results of a phase II, placebo-controlled trial of atrasentan (Xinlay) in patients with early-stage, hormone-naive prostate cancer. Researchers found that both placebo and drug recipients showed an extended PSADT of similar length.

Atlanta-PSA doubling time (PSADT) appears to have limitations as a predictor of treatment outcome, according to results of a phase II, placebo-controlled trial of atrasentan (Xinlay) in patients with early-stage, hormone-naive prostate cancer. Researchers found that both placebo and drug recipients showed an extended PSADT of similar length.

Both PSA and PSADT are used to monitor progression after primary therapy for prostate cancer. In addition, PSADT is commonly used to measure the effect of intervention in clinical trials, many of which are uncontrolled phase II trials, Dr. Nelson said.

Results were presented at the American Society of Clinical Oncology annual meeting here.

PSA progression was evaluated at weeks 6 and 12 and every 12 weeks thereafter. Patients were treated until PSA progression occurred or until the last man enrolled had been treated for 12 months. On-treatment PSADT was compared between treatment groups in patients with at least three on-treatment PSA values collected every 12 weeks while on the study drug. Mean change from baseline in PSA velocity was analyzed using a one-time analysis of variance with treatment as the factor.

Baseline PSA was lower in patients who received placebo than in patients treated with atrasentan (mean, 1.4 ng/mL vs.1.8 ng/mL, p=.012). On-treatment PSADT compared with baseline lengthened in a similar fashion in 78% of patients in the placebo group and in 68% of those treated with atrasentan.

PSA velocity was protracted for patients in both treatment arms. Mean baseline slope compared with mean on-treatment slope was 1.47 versus 0.96 (p<.001) in the placebo group and 1.56 versus 1.26 (p=.017) in the atrasentan-treated group.

"In clinical trials using PSADT as a measure of effect in localized prostate cancer, controlling for baseline PSA variables is required at randomization to avoid unexpected bias," Dr. Nelson said. "A control arm is essential to accurately interpret the treatment effect of PSADT."

Dr. Nelson has been a consultant to Abbott Laboratories, the sponsor of this trial.