Prostate Adenocarcinoma TransCutaneous Hormones

Summary

RATIONALE: The increasingly prolonged and extended use of androgen deprivation therapy (ADT) in the treatment of prostate cancer, usually achieved through the administration of LHRH agonists, has raised concerns about long-term toxicities, in particular osteoporosis and adverse metabolic changes which may be associated with type II diabetes and increased cardiovascular risk. An alternative approach is to investigate other methods of ADT. Oral oestrogen has been shown to be as effective as LHRH and surgical orchidectomy in achieving castrate levels of testosterone and has equivalent or improved prostate cancer outcomes but is not used routinely as first-line therapy because of the risk of cardiovascular system (CVS) complications. The CVS complications have been attributed to first-pass hepatic metabolism. Administering oestrogen parenterally avoids the entero-hepatic circulation and so is expected to mitigate the risk of CVS toxicity whilst still effectively suppressing testosterone to castrate levels. This hypothesis has been supported by results from the early stages of this trial which have provided sufficient indication of the safety and efficacy of the patches to warrant further investigation of the treatment in this setting, as recommended by the IDMC.. PURPOSE: This randomized phase III trial is studying how well the estrogen skin patch works compared with luteinizing hormone-releasing hormone agonist injections in treating patients with locally advanced or metastatic prostate cancer.

Timeline

Start

2006-03

Primary completion

2021-08

Completion

2021-08

Publications

• Langley RE, Gilbert DC, Mangar S, Rosen S, Bourmaki E, Rush HL, Kananga Sundaram S, Alhasso A, Kockelbergh R, Abdel-Aty H, Amos CL, Brown L, Brown S, Carvalho C, Chan K, Collins G, Cross W, Deighan J, Dixit S, Duong T, Dyer J, Gale J, Gillessen S, Griffiths A, Laniado M, Lydon A, McPhail N, MacNair A, Madaan S, Marshall J, Matheson D, Millman R, Mohamed W, Murphy L, Narahari K, Parker C, Panades M, Pope A, Raval A, Robinson A, Russell M, Scrase C, Sydes M, Turo R, Venkitaraman R, Wade S, Kynaston H, Attard G, James ND, Clarke N, Parmar MK, Nankivell M; STAMPEDE-1 and PATCH Investigators. Transdermal Estradiol Patches in Locally Advanced Prostate Cancer. N Engl J Med. 2026 Apr 23;394(16):1595-1607. doi: 10.1056/NEJMoa2511781. Epub 2026 Mar 25.
• Gilbert DC, Nankivell M, Rush H, Clarke NW, Mangar S, Al-Hasso A, Rosen S, Kockelbergh R, Sundaram SK, Dixit S, Laniado M, McPhail N, Shaheen A, Brown S, Gale J, Deighan J, Marshall J, Duong T, Macnair A, Griffiths A, Amos CL, Sydes MR, James ND, Parmar MKB, Langley RE. A Repurposing Programme Evaluating Transdermal Oestradiol Patches for the Treatment of Prostate Cancer Within the PATCH and STAMPEDE Trials: Current Results and Adapting Trial Design. Clin Oncol (R Coll Radiol). 2024 Jan;36(1):e11-e19. doi: 10.1016/j.clon.2023.10.054. Epub 2023 Nov 8.
• Gilbert DC, Duong T, Sydes M, Bara A, Clarke N, Abel P, James N, Langley R, Parmar M; STAMPEDE and PATCH Trial Management Groups. Transdermal oestradiol as a method of androgen suppression for prostate cancer within the STAMPEDE trial platform. BJU Int. 2018 May;121(5):680-683. doi: 10.1111/bju.14153. Epub 2018 Feb 28. No abstract available.
• Langley RE, Kynaston HG, Alhasso AA, Duong T, Paez EM, Jovic G, Scrase CD, Robertson A, Cafferty F, Welland A, Carpenter R, Honeyfield L, Abel RL, Stone M, Parmar MK, Abel PD. A Randomised Comparison Evaluating Changes in Bone Mineral Density in Advanced Prostate Cancer: Luteinising Hormone-releasing Hormone Agonists Versus Transdermal Oestradiol. Eur Urol. 2016 Jun;69(6):1016-25. doi: 10.1016/j.eururo.2015.11.030. Epub 2015 Dec 17.
• Langley RE, Cafferty FH, Alhasso AA, Rosen SD, Sundaram SK, Freeman SC, Pollock P, Jinks RC, Godsland IF, Kockelbergh R, Clarke NW, Kynaston HG, Parmar MK, Abel PD. Cardiovascular outcomes in patients with locally advanced and metastatic prostate cancer treated with luteinising-hormone-releasing-hormone agonists or transdermal oestrogen: the randomised, phase 2 MRC PATCH trial (PR09). Lancet Oncol. 2013 Apr;14(4):306-16. doi: 10.1016/S1470-2045(13)70025-1. Epub 2013 Mar 4.

Drugs

Indications