E J Small1, N J Vogelzang. 1. Department of Medicine, University of California, San Francisco 94115, USA. ericvvsmall@QUICKMAIL.UCSF.edu
Abstract
PURPOSE: To discuss the evolution of new concepts in the Use of second-line hormonal therapy for patients with progressive prostate cancer despite androgen deprivation. DESIGN: Pertinent contemporary prostate-specific antigen (PSA)-based reports of the utility of secondary hormonal maneuvers after treatment with combined androgen blockade (CAB) were reviewed. RESULTS: The use of PSA as an end point in hormonerefractory prostate cancer (HRPC) trials is more widely accepted, but still remains somewhat controversial. Using PSA as an end point, it is clear that a variety of secondary hormonal maneuvers can result in responses. Antiandrogen withdrawal is efficacious in approximately 20% of patients and can be observed with a variety of antiandrogens, including flutamide, bicalutamide, and megestrol acetate. A variety of regimens, including megestrol, bicalutamide, glucocorticoids, aminoglutethimide, and ketoconazole, retain activity (14% to 75% PSA response proportion) even in patients who have failed to respond to CAB and flutamide withdrawal. CONCLUSION: Once CAB (suppression of gonadal and adrenal androgen) is undertaken, further hormonal maneuvers remain efficacious in some patients with progressive prostate cancer. Antiandrogen withdrawal is now a mandatory maneuver before proceeding to other regimens. It is clear that certain patients will continue to respond to hormonal maneuvers even after antiandrogen withdrawal. An understanding of the molecular basis of these responses may result in the development of a more targeted therapy in the future.
PURPOSE: To discuss the evolution of new concepts in the Use of second-line hormonal therapy for patients with progressive prostate cancer despite androgen deprivation. DESIGN: Pertinent contemporary prostate-specific antigen (PSA)-based reports of the utility of secondary hormonal maneuvers after treatment with combined androgen blockade (CAB) were reviewed. RESULTS: The use of PSA as an end point in hormonerefractory prostate cancer (HRPC) trials is more widely accepted, but still remains somewhat controversial. Using PSA as an end point, it is clear that a variety of secondary hormonal maneuvers can result in responses. Antiandrogen withdrawal is efficacious in approximately 20% of patients and can be observed with a variety of antiandrogens, including flutamide, bicalutamide, and megestrol acetate. A variety of regimens, including megestrol, bicalutamide, glucocorticoids, aminoglutethimide, and ketoconazole, retain activity (14% to 75% PSA response proportion) even in patients who have failed to respond to CAB and flutamide withdrawal. CONCLUSION: Once CAB (suppression of gonadal and adrenal androgen) is undertaken, further hormonal maneuvers remain efficacious in some patients with progressive prostate cancer. Antiandrogen withdrawal is now a mandatory maneuver before proceeding to other regimens. It is clear that certain patients will continue to respond to hormonal maneuvers even after antiandrogen withdrawal. An understanding of the molecular basis of these responses may result in the development of a more targeted therapy in the future.
Authors: Howard I Scher; Tomasz M Beer; Celestia S Higano; Aseem Anand; Mary-Ellen Taplin; Eleni Efstathiou; Dana Rathkopf; Julia Shelkey; Evan Y Yu; Joshi Alumkal; David Hung; Mohammad Hirmand; Lynn Seely; Michael J Morris; Daniel C Danila; John Humm; Steve Larson; Martin Fleisher; Charles L Sawyers Journal: Lancet Date: 2010-04-14 Impact factor: 79.321
Authors: Charles J Ryan; Matthew R Smith; Johann S de Bono; Arturo Molina; Christopher J Logothetis; Paul de Souza; Karim Fizazi; Paul Mainwaring; Josep M Piulats; Siobhan Ng; Joan Carles; Peter F A Mulders; Ethan Basch; Eric J Small; Fred Saad; Dirk Schrijvers; Hendrik Van Poppel; Som D Mukherjee; Henrik Suttmann; Winald R Gerritsen; Thomas W Flaig; Daniel J George; Evan Y Yu; Eleni Efstathiou; Allan Pantuck; Eric Winquist; Celestia S Higano; Mary-Ellen Taplin; Youn Park; Thian Kheoh; Thomas Griffin; Howard I Scher; Dana E Rathkopf Journal: N Engl J Med Date: 2012-12-10 Impact factor: 91.245