U.S. Oncology Research, Inc., Texas Oncology and Baylor College of Medicine, Webster, TX 77598, USA.
Urol Oncol. 2012 Sep;30(5):607-13. doi: 10.1016/j.urolonc.2010.07.002. Epub 2010 Oct 2.
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.
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.
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.
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.
在接受化疗的转移性去势抵抗性前列腺癌（CRPC）男性患者中，血清碱性磷酸酶（ALP）变化与总生存期（OS）的关系尚不清楚。我们评估了 TAX327 试验中接受多西他赛或米托蒽醌治疗的 CRPC 伴骨转移男性患者 90 天内 ALP 变化与 OS 的关系。
符合条件的患者包括有骨转移疾病、基线 ALP≥120u/L（正常值上限）和有 2 次以上 ALP 治疗后测量值的患者。使用 Kaplan-Meier 方法估计生存情况，并使用 Cox 比例风险回归评估 ALP 变化的预后潜力。通过似然减少因子计算替代物。
601 名患者符合入选标准。到第 90 天，159 名患者 ALP 正常化（<120u/L），442 名患者未正常化。在调整第 90 天 PSA 下降≥30%后，ALP 正常化仍然是 OS 的预后因素（HR 0.79，95%CI=0.65-0.97，P=0.022）。在调整第 90 天 PSA 增加≥50%后，ALP 增加仍然是 OS 的预后因素（HR 1.69，95%CI=1.33-2.14，P<0.001）。ALP 变化不符合 OS 替代物的标准。
对于接受多西他赛或米托蒽醌化疗的 CRPC、骨转移和高基线 ALP 的男性患者，第 90 天 ALP 正常化是独立于≥30%PSA 下降的更好生存的预测因素。第 90 天 ALP 增加也与不良生存独立相关，而与≥50%PSA 增加无关。鉴于 ALP 易于获得，我们的数据需要验证。
