Edelman M J, Meyers F J, Grennan T, Lauder J, Doroshow J
Division of Hematology/Oncology, UC Davis School of Medicine, Sacramento, CA, USA.
Invest New Drugs. 1998;16(2):179-82. doi: 10.1023/a:1006097109088.
No effective therapy has been demonstrated for hormone refractory prostate cancer (HRPC). Pyrazine diazohydroxide (PZDH) is a novel antineoplastic agent with a broad range of activity in preclinical studies and a moderate toxicity profile in Phase I trials. We undertook a Phase II study of PZDH in HRPC utilizing decline in PSA as the primary end point. Fifteen patients were enrolled, median age of 70 (55-86), median pretherapy PSA 206 ng/ml (range 42-10,000). Four patients were African American. Sites of disease: bone only 7, soft tissue only 2, both 6. All were evaluable for toxicity and response. PZDH was administered at 250 mg/m2 i.v. every three weeks. The median number of cycles administered was two (range 1-6). Toxicity was mild, with only one patient manifesting serious (grade 3-4) toxicity. Unfortunately, activity was minimal with only a single patient demonstrating a >75% decline in PSA. As this patient's PSA began to rise almost immediately the response was considered transient and not felt to justify pursuing a second stage of the trial. Supporting this conclusion was the disappointing median survival of 220 days. In summary, we conclude that PZDH, while well tolerated at this dose and schedule has only minimal activity in HRPC.
对于激素难治性前列腺癌（HRPC），尚未证实有有效的治疗方法。吡嗪重氮氢氧化物（PZDH）是一种新型抗肿瘤药物，在临床前研究中具有广泛的活性，在I期试验中具有中等毒性。我们进行了一项PZDH治疗HRPC的II期研究，以PSA下降作为主要终点。招募了15名患者，中位年龄70岁（55 - 86岁），治疗前PSA中位数为206 ng/ml（范围42 - 10,000）。4名患者为非裔美国人。疾病部位：仅骨转移7例，仅软组织转移2例，两者皆有6例。所有患者均可评估毒性和反应。PZDH以250 mg/m²静脉注射，每三周一次。给药周期中位数为两个（范围1 - 6）。毒性轻微，仅有1例患者出现严重（3 - 级4）毒性。不幸地是，活性极小，仅有1例患者PSA下降>75%。由于该患者的PSA几乎立即开始上升，因此该反应被认为是短暂的，不值得进行试验的第二阶段。支持这一结论的是令人失望的220天中位生存期。总之，我们得出结论，PZDH虽然在此剂量和给药方案下耐受性良好，但在HRPC中仅有极小的活性。
