TY - JOUR
T1 - Serum alkaline phosphatase changes predict survival independent of PSA changes in men with castration-resistant prostate cancer and bone metastasis receiving chemotherapy
AU - Sonpavde, Guru
AU - Pond, Gregory R.
AU - Berry, William R.
AU - de Wit, Ronald
AU - Armstrong, Andrew J.
AU - Eisenberger, Mario A.
AU - Tannock, Ian F.
N1 - Funding Information:
This study was supported, in part, by Sanofi-Aventis and was presented, in part, as a poster at the Genitourinary Cancer Symposium in San Francisco in 2010, and the ASCO (American Society of Clinical Oncology) annual meeting in Chicago in 2010.
Funding Information:
Guru Sonpavde, M.D.: Speakers' bureau and honoraria from Sanofi-Aventis; William R. Berry, M.D.: Speakers' bureau and honoraria from Sanofi-Aventis; Ronald de Wit, M.D.: Consultant, Advisory Board, Research support, Speakers' bureau and honoraria from Sanofi-Aventis; Andrew J. Armstrong: research funding, Speakers bureau and honoraria from Sanofi-Aventis; Mario A. Eisenberger, M.D.: Consultant, Advisory Board, research support from Sanofi-Aventis; Ian F. Tannock, M.D.: research funding from Sanofi-Aventis.
Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2012/9
Y1 - 2012/9
N2 - Objectives: The association of a change in serum alkaline phosphatase (ALP) with overall survival OS in men with metastatic castration-resistant prostate cancer (CRPC) receiving chemotherapy is unknown. We evaluated the association of changes in ALP within 90 days with OS in men with CRPC and bone metastases treated with docetaxel or mitoxantrone in the TAX327 trial. Materials and methods: Eligible patients included those with bony metastatic disease, baseline ALP ≥ 120 u/L (upper limit of normal) and ≥2 post-therapy measurements of ALP available. Survival was estimated using the Kaplan-Meier method and prognostic potential of change in ALP was evaluated using Cox proportional hazards regression. Surrogacy was calculated by the Likelihood Reduction Factor. Results: 601 patients met the eligibility criteria. By day 90, 159 patients had ALP normalization (<120 u/L) and 442 patients did not normalize. Normalization of ALP remained prognostic for OS after adjusting for PSA decline ≥ 30% by day 90 (HR 0.79, 95% CI = 0.65-0.97, P = 0.022). Increase in ALP remained prognostic for OS when adjusting for PSA increase ≥ 50% by day 90 (HR 1.69, 95% CI = 1.33-2.14, P < 0.001). ALP changes did not meet criteria for surrogacy for OS. Conclusions: For men with CRPC, bone metastasis and high baseline ALP receiving docetaxel or mitoxantrone chemotherapy, normalization of ALP by day 90 was predictive of better survival independent of ≥30% PSA declines. An increase in ALP by day 90 was also predictive of poor survival independent of ≥50% PSA increase. Given the ready availability of ALP, the validation of our data is warranted.
AB - Objectives: The association of a change in serum alkaline phosphatase (ALP) with overall survival OS in men with metastatic castration-resistant prostate cancer (CRPC) receiving chemotherapy is unknown. We evaluated the association of changes in ALP within 90 days with OS in men with CRPC and bone metastases treated with docetaxel or mitoxantrone in the TAX327 trial. Materials and methods: Eligible patients included those with bony metastatic disease, baseline ALP ≥ 120 u/L (upper limit of normal) and ≥2 post-therapy measurements of ALP available. Survival was estimated using the Kaplan-Meier method and prognostic potential of change in ALP was evaluated using Cox proportional hazards regression. Surrogacy was calculated by the Likelihood Reduction Factor. Results: 601 patients met the eligibility criteria. By day 90, 159 patients had ALP normalization (<120 u/L) and 442 patients did not normalize. Normalization of ALP remained prognostic for OS after adjusting for PSA decline ≥ 30% by day 90 (HR 0.79, 95% CI = 0.65-0.97, P = 0.022). Increase in ALP remained prognostic for OS when adjusting for PSA increase ≥ 50% by day 90 (HR 1.69, 95% CI = 1.33-2.14, P < 0.001). ALP changes did not meet criteria for surrogacy for OS. Conclusions: For men with CRPC, bone metastasis and high baseline ALP receiving docetaxel or mitoxantrone chemotherapy, normalization of ALP by day 90 was predictive of better survival independent of ≥30% PSA declines. An increase in ALP by day 90 was also predictive of poor survival independent of ≥50% PSA increase. Given the ready availability of ALP, the validation of our data is warranted.
KW - Bone metastasis
KW - Castration-resistant prostate cancer
KW - Overall survival
KW - PSA
KW - Serum alkaline phosphatase
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UR - http://www.scopus.com/inward/citedby.url?scp=84866745304&partnerID=8YFLogxK
U2 - 10.1016/j.urolonc.2010.07.002
DO - 10.1016/j.urolonc.2010.07.002
M3 - Article
C2 - 20888271
AN - SCOPUS:84866745304
SN - 1078-1439
VL - 30
SP - 607
EP - 613
JO - Urologic Oncology: Seminars and Original Investigations
JF - Urologic Oncology: Seminars and Original Investigations
IS - 5
ER -