Can prostate-specific antigen be used as a valid end point to determine the efficacy of chemotherapy for advanced prostate cancer?
✍ Scribed by B. Seckin; C. T. Anthony; B. Murphy; M. S. Steiner
- Publisher
- Springer-Verlag
- Year
- 1996
- Tongue
- English
- Weight
- 444 KB
- Volume
- 14
- Category
- Article
- ISSN
- 0724-4983
No coin nor oath required. For personal study only.
✦ Synopsis
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.
Prostate-specific antigen (PSA) is produced only by epithelial cells that line the acini and ducts of the prostate gland and, thus, is prostate-specific [11]. PSA is normally found in low amounts in serum and, clinically, its elevation may lead to the early diagnosis of prostate cancer. PSA may have value in the early detection and screening of prostate cancer, in the staging of prostate cancer, in monitoring of patients for cancer recurrence after radiation or radical prostatectomy, and in assessment of the efficacy of androgen deprivation therapy in patients who have advanced prostate cancer [11]. What remains unclear, however, is whether PSA may be used as a measur-