Patel Hiral, Mick Rosemarie, Finlay Jarod, Zhu Timothy C, Rickter Elizabeth, Cengel Keith A, Malkowicz S Bruce, Hahn Stephen M, Busch Theresa M
Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6072, USA.
Clin Cancer Res. 2008 Aug 1;14(15):4869-76. doi: 10.1158/1078-0432.CCR-08-0317.
The time course of serum prostate-specific antigen (PSA) response to photodynamic therapy (PDT) of prostate cancer was measured.
Seventeen patients were treated in a phase I trial of motexafin lutetium-PDT. PDT dose was calculated in each patient as the product of the ex vivo measured pre-PDT photosensitizer level and the in situ measured light dose. Serum PSA level was measured within 2 months before PDT (baseline), and at day 1; weeks 1 to 3; months 1, 2, and 3; months 4 to 6; and months 7 to 11 after PDT.
At 24 hours after PDT, serum PSA increased by 98% +/- 36% (mean +/- SE) relative to baseline levels (P = 0.007). When patients were dichotomized based on median PDT dose, those who received high PDT dose showed a 119% +/- 52% increase in PSA compared with a 54% +/- 27% increase in patients treated at low PDT dose. Patients treated with high versus low PDT dose showed a median biochemical delay of 82 versus 43 days (P = 0.024), with biochemical delay defined as the length of time between PDT and a nonreversible increase in PSA to a value greater than or equal to baseline.
Results show PDT to induce large, transient increases in serum PSA levels. Patients who experienced high PDT dose showed greater short-term increase in PSA and a significantly more durable PSA response (biochemical delay). These data strongly promote the need for individualized delivery of PDT dose and assessment of treatment effect in PDT of prostate cancer. Information gained from such patient-specific measurements could facilitate the introduction of multiple PDT sessions in patients who would benefit.
测定血清前列腺特异性抗原(PSA)对前列腺癌光动力疗法(PDT)反应的时间进程。
17例患者参与了钆镓酸莫特沙芬-PDT的I期试验。每位患者的PDT剂量通过体外测量的PDT前光敏剂水平与原位测量的光剂量的乘积来计算。在PDT前2个月内(基线)、第1天、第1至3周、第1、2和3个月、第4至6个月以及PDT后第7至11个月测量血清PSA水平。
PDT后24小时,血清PSA相对于基线水平增加了98%±36%(平均值±标准误)(P = 0.007)。根据PDT剂量中位数将患者分为两组,接受高PDT剂量的患者PSA增加了119%±52%,而接受低PDT剂量治疗的患者PSA增加了54%±27%。高PDT剂量组与低PDT剂量组患者的中位生化延迟分别为82天和43天(P = 0.024),生化延迟定义为从PDT到PSA不可逆增加至大于或等于基线值的时间长度。
结果显示PDT可导致血清PSA水平大幅、短暂升高。接受高PDT剂量的患者PSA短期升高幅度更大,且PSA反应(生化延迟)更持久。这些数据有力地表明在前列腺癌PDT中需要个体化给予PDT剂量并评估治疗效果。从这些针对患者的测量中获得的信息有助于在可能受益的患者中引入多次PDT治疗疗程。