Smith Matthew R, Manola Judith, Kaufman Donald S, George Daniel, Oh William K, Mueller Elisabetta, Slovin Susan, Spiegelman Bruce, Small Eric, Kantoff Philip W
Division of Hematology and Medical Oncology, Massachusetts General Hospital, Boston 02114, USA.
Cancer. 2004 Oct 1;101(7):1569-74. doi: 10.1002/cncr.20493.
The objective of this study was to assess the biologic activity of rosiglitazone, a peroxisome proliferator-activated receptor gamma agonist that has been approved to treat type 2 diabetes, in men with recurrent prostate carcinoma using change in prostate specific antigen (PSA) doubling time (PSADT) as the primary outcome variable.
Men with histologically confirmed prostate carcinoma, no recent hormone therapy, a rising serum PSA level after radical prostatectomy and/or radiation therapy, and no radiographic evidence of metastases were assigned randomly to receive either oral rosiglitazone (4 mg twice daily) or placebo. The treatment was continued until the men developed disease progression or adverse effects. A positive outcome was defined as a posttreatment PSADT > 150% the baseline PSADT and no new metastases.
One hundred six men were enrolled. The median treatment duration was 315 days for men in the placebo group and 338 days for men in the rosiglitazone group (P = 0.28). Forty percent of men in the in the placebo group and 38% of men in the rosiglitazone group had a posttreatment PSADT > 150% of the baseline PSADT and no new metastases (P = 1.00). In exploratory analyses, the rate of a positive outcome remained higher than expected in the placebo group, even when a positive outcome was redefined using more stringent criteria. The time to disease progression was similar between the groups.
Rosiglitazone did not increase PSADT or prolong the time to disease progression more than placebo in men with a rising PSA level after radical prostatectomy and/or radiation therapy. The unexpected discordance between baseline and posttreatment PSADT in the placebo group reinforced the importance of randomized controlled trials in this setting.
本研究的目的是，使用前列腺特异性抗原（PSA）倍增时间（PSADT）的变化作为主要结局变量，评估已被批准用于治疗2型糖尿病的过氧化物酶体增殖物激活受体γ激动剂罗格列酮，对复发性前列腺癌男性患者的生物学活性。
组织学确诊为前列腺癌、近期未接受激素治疗、根治性前列腺切除术和/或放射治疗后血清PSA水平升高且无影像学转移证据的男性患者，被随机分配接受口服罗格列酮（每日两次，每次4 mg）或安慰剂。治疗持续至患者出现疾病进展或不良反应。阳性结局定义为治疗后PSADT>基线PSADT的150%且无新的转移灶。
106名男性患者入组。安慰剂组患者的中位治疗持续时间为315天，罗格列酮组为338天（P = 0.28）。安慰剂组40%的男性患者和罗格列酮组38%的男性患者治疗后PSADT>基线PSADT的150%且无新的转移灶（P = 1.00）。在探索性分析中，即使使用更严格的标准重新定义阳性结局，安慰剂组的阳性结局发生率仍高于预期。两组间疾病进展时间相似。
对于根治性前列腺切除术和/或放射治疗后PSA水平升高的男性患者，罗格列酮与安慰剂相比，并未增加PSADT或延长疾病进展时间。安慰剂组基线和治疗后PSADT之间意外的不一致，强化了在此情况下进行随机对照试验的重要性。
