title: Can prostate-specific antigen be used as a valid end point to determine the efficacy of chemotherapy for advanced prostate cancer?
abstract: It is current practice in many clinical trials evaluating new chemotherapy regimens for the treatment of advanced prostate cancer to use prostate-specific antigen (PSA) decline as a response criteria with the assumption that the level of PSA reflects the efficacy of chemotherapy. Advanced prostate cancer is heterogeneous; therefore, the validity of PSA decline as a measurable end point was studied in advanced human prostate-cancer cell lines: androgen-sensitive LNCaP and androgen-insensitive PC3 cells. Each cell line was grown for 4 days with escalating doses of Adriamycin or vinblastine. Cell counts, intracellular PSA concentrations, and secreted PSA levels were determined daily for 4 days. Untreated LNCaP cells had constant secretion of PSA per cell. In contrast, LNCaP cells treated with Adriamycin or vinblastine had an 80% reduction in cell numbers and a 3-fold increase in secreted PSA per cell by day 4. In contrast, PC3 cells had a different response to Adriamycin and vinblastine. Both drugs reduced cell numbers by 97% of control values and suppressed PSA production in the remaining viable cells by 4 days in culture. Thus, prostate-cancer cell production of PSA is variable with chemotherapy and the PSA level may not accurately reflect the actual tumor response to chemotherapy.
authors: Department of Urology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors: B
authors: B
authors: Seckin
authors: C T
authors: CT
authors: Anthony
authors: B
authors: B
authors: Murphy
authors: M S
authors: MS
authors: Steiner
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival; D018450:Disease Progression; D004317:Doxorubicin / Q000494:pharmacology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011467:Prostate / Q000166:cytology / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000494:pharmacology*
chemical_list: D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D004317:Doxorubicin; D017430:Prostate-Specific Antigen