Evaluation of Prostate-Specific Antigen Declines for Surrogacy in Patients Treated on SWOG 99-16

摘要: Background: The identification of surrogate endpoints that can replace true outcome is crucial to the rapid evaluation new cancer drugs. Retrospective analyses phase II and III trials in metastatic androgen-independent prostate have shown associations between declines serum prostate-specific antigen (PSA) levels survival. We evaluated PSA changes as potential markers for survival by using data from a clinical trial. Methods: Men with were randomly assigned either docetaxel/estramustine (D/E) or mitoxantrone/ prednisone (M/P) treatment on Southwest Oncology Group Protocol 99-16. Of 674 eligible patients, 551 had baseline measurement at least one during first 3 months protocol. level 5%-90% velocity 1, 2, tested surrogacy three statistical criteria: Prentice's criteria, proportion effect explained, variation explained. All tests two-sided. Results: Three-month 20%-40%, 2-month decline 30%, 2 met all criteria. For example, 3-month 30% was associated more than 50% decrease risk death compared lack such (hazard ratio [HR]= 0.43, 95% confidence interval [CI] = 0.34 0.55; P<.001), increased men treated M/P D/E (HR 1.24, CI 1.02 1.51; P =.032) lost significance after adjustment this surrogate, whereas remained statistically significant treatment. 50%, commonly reported trials, did not meet criteria surrogacy. Conclusions: Several measures satisfied retrospective analysis SWOG However, these await prospective validation future chemotherapy cancer.