"A Phase III Protocol of Androgen Suppression (AS) and 3DCRT/IMRT Vs AS and 3DCRT/IMRT Followed by Chemotherapy With Docetaxel and Prednisone for Localized, High-Risk Prostate Cancer
Pts: 1) Gleason >=9 and PSA <= 150, Any T stage, 2) Gleason 8, PSA <20, T2 or higher, 3) Gleason 7-8, PSA 20-150, Any T stage. Clinically negative LN.
Arm 1: AS (LHRH agonist + oral antiandrogen) x 8 weeks, followed by RT to 72-75.6 Gy with concurrent AS. Continue LHRH for total of 24 months. Arm 2: Arm 1 plus 6 cycles of docetaxel (q3w) and daily prednisone 28 days after completion of RT.
2015ASCO GU Symposium 2015 -- "A phase III protocol of androgen suppression (AS) and 3DCRT/IMRT versus AS and 3DCRT/IMRT followed by chemotherapy (CT) with docetaxel and prednisone for localized, high-risk prostate cancer (RTOG 0521)." (Sandler HM et al, ASCO GU 2015)
4yOS 89% AS+RT vs. 93% AS+RT+CT (HR=0.68, p=.03)
5y DFS66% AS+RT vs 73% AS+RT+CT (HR=0.76, p=.05)
Fewer deaths due to prostate cancer/treatment and other causes in AS+RT+CT arm
Nihon University, Japan (2003-2006) -- RT + ADT +/- estramustine
Randomized. 39 patients, intermediate/high risk PCA by NCCN guidelines. Arm 1) Neoadjuvant/concurrent LHRH agonist + estramustine x6 months vs Arm 2) NCAHT x 6 months. Both groups 3D-CRT 70/35
2010PMID 19449118 -- "Neoadjuvant LHRH analog plus estramustine phosphate combined with three-dimensional conformal radiotherapy for intermediate- to high-risk prostate cancer: a randomized study." (Hirano D, Int Urol Nephrol. 2010 Mar;42(1):81-8. Epub 2009 May 16.) Median F/U 2.3 years
Outcome: 4-year bRFS ADT+EMP 61% vs ADT alone 49% (SS)
Toxicity: No severe toxicities
Conclusion: ADT + EMP better than ADT alone, but either arm insufficient and dose escalation or adjuvant ADT needed
Randomized. Closed early due to thromobembolic events. 397 patients. High risk CaP (PSA 20-100 and GS >=7, or T2+, GS8, PSA <100). Neoadjuvant/concurrent and adjuvant AS + RT (2/2/2 TAA) +/- TEE Chemotherapy (taxol, estramustine, etoposide) x 4 cycles.
2009PMID 18990504 -- "Phase III multi-institutional trial of adjuvant chemotherapy with paclitaxel, estramustine, and oral etoposide combined with long-term androgen suppression therapy and radiotherapy versus long-term androgen suppression plus radiotherapy alone for high-risk prostate cancer: preliminary toxicity analysis of RTOG 99-02." (Rosenthal SA, Int J Radiat Oncol Biol Phys. 2009 Mar 1;73(3):672-8. Epub 2008 Nov 5.)
Toxicity: AS 37% vs. AS + TEE 715 (SS), for hematological (SS), GI (SS), and trend GU (p=0.07). Three cases of MDS/AML in TEE arm
Conclusion: TEE associated with significantly increased toxicity during treatment
University of North Carolina - PMID 16609031 - "A phase II trial of celecoxib in prostate-specific antigen recurrent prostate cancer after definitive radiation therapy or radical prostatectomy" (Pruthi RS, Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2172-7.)
40 pts. Celecoxib (Celebrex) 400 mg/day. 36 of 40 (90%) had a slowing of PSA; 11 of 40 with decline in PSA, 8 with stable disease.