Olbert Peter Jochen, Hegele Axel, Kraeuter Petra, Heidenreich Axel, Hofmann Rainer, Schrader Andres Jan
Department of Urology and Pediatric Urology, Philipps University Medical School, Baldingerstrasse, 35043 Marburg, Germany.
Anticancer Drugs. 2006 Sep;17(8):993-6. doi: 10.1097/01.cad.0000231468.69535.97.
Docetaxel has shown promise for the treatment of hormone-refractory prostate cancer and has become the standard of care. The flare phenomenon is a known entity in androgen-deprivation therapy of advanced prostate cancer and it has also been described in palliative chemotherapy of hormone-refractory prostate cancer. The aim of this study was to evaluate the clinical impact of a prostate-specific antigen flare phenomenon in docetaxel-treated hormone-refractory prostate cancer patients. From December 2002 to August 2005, we treated 44 patients with hormone-refractory prostate cancer applying docetaxel-based regimens. Prostate-specific antigen levels were determined before therapy and weekly thereafter. Patients were divided into three groups: response (group 1), progression (group 2) and flare (group 3). Flare was defined as initially rising prostate-specific antigen under therapy, dropping thereafter to values below baseline. The groups were compared for overall survival by Kaplan-Meier analysis. We observed a prostate-specific antigen flare phenomenon in eight (18%) of 44 evaluable patients; 24 (54.5%) patients were primary responders and 12 (27.3%) experienced progressive disease. In group 3, prostate-specific antigen levels rose to 107-180% from baseline and then dropped to 21-68%. Kaplan-Meier analysis showed significantly better overall median survival for groups 1 (18 months, P=0.0005) and 3 (19 months, P=0.006) than for group 2 (7 months). Survival in groups 1 and 3 was comparable. Grade 3 and 4 toxicity was below 5% and equally distributed between the 3 groups. In our limited patient cohort, prostate-specific antigen flare phenomenon does not seem to be a clinically relevant issue in terms of overall survival. Thus, an initial rise of prostate-specific antigen under docetaxel therapy in hormone-refractory prostate cancer does not indicate therapeutic failure and should not lead to early withdrawal from therapy in the absence of clinical signs of progression.
多西他赛已显示出对激素难治性前列腺癌治疗的前景,并已成为治疗的标准方法。在晚期前列腺癌的雄激素剥夺治疗中,“flare现象”是一个已知的情况,在激素难治性前列腺癌的姑息化疗中也有描述。本研究的目的是评估在接受多西他赛治疗的激素难治性前列腺癌患者中前列腺特异性抗原“flare现象”的临床影响。从2002年12月至2005年8月,我们采用基于多西他赛的方案治疗了44例激素难治性前列腺癌患者。在治疗前及之后每周测定前列腺特异性抗原水平。患者分为三组:缓解组(第1组)、进展组(第2组)和“flare组”(第3组)。“flare”定义为治疗期间前列腺特异性抗原最初升高,随后降至基线以下。通过Kaplan-Meier分析比较三组的总生存期。我们在44例可评估患者中的8例(18%)观察到前列腺特异性抗原“flare现象”;24例(54.5%)患者为初始缓解者,12例(27.3%)经历疾病进展。在第3组中,前列腺特异性抗原水平从基线上升至107 - 180%,然后降至21 - 68%。Kaplan-Meier分析显示第1组(18个月,P = 0.0005)和第3组(19个月,P = 0.006)的总中位生存期明显优于第2组(7个月)。第1组和第3组的生存期相当。3级和4级毒性低于5%,且在三组中分布均匀。在我们有限的患者队列中,就总生存期而言,前列腺特异性抗原“flare现象”似乎不是一个临床相关问题。因此,在激素难治性前列腺癌中,多西他赛治疗期间前列腺特异性抗原的初始升高并不表明治疗失败,在没有临床进展迹象的情况下不应导致过早停药。