Oncology Unit 2, University Hospital of Pisa, Pisa, Italy.
Cancer. 2014 Dec 15;120(24):3923-31. doi: 10.1002/cncr.28953. Epub 2014 Aug 8.
Docetaxel plus prednisone is currently the standard first-line treatment in metastatic castration-resistant prostate cancer (mCRPC). The aim of this study was to assess the clinical activity and pharmacodynamic/pharmacogenetic profile of docetaxel plus prednisone in combination with metronomic cyclophosphamide in mCRPC patients.
Forty-one chemotherapy-naive patients received docetaxel (60 mg/m(2) intravenously every 3 weeks up to 12 cycles) and, from day 2, prednisone 10 mg/day, celecoxib 400 mg/day, and metronomic cyclophosphamide 50 mg/day, continuously. Plasma VEGF and bFGF were detected by ELISA. Real-time PCR-SNP analysis of VEGF gene was performed using an ABI PRISM 7900HT SDS and TaqMan SNP genotyping.
Eighty-seven percent of patients were free of progression at 6 months. A decrease in prostate-specific antigen ≥50% was observed in 82% of 39 evaluable patients, with a median time to progression of 12.3 months. Grade 3 adverse events were neutropenia (5%), thrombocytopenia, diarrhea, and stomatitis (2.5%). Median PFS and OS were 14.9 months (95% CI, 9.2-15.3 months) and 33.3 months (95% CI, 23-35.6 months), respectively. Of 11 patients (28%) with evaluable disease, 5 (44%) achieved a complete response, 2 (11%) a partial response, and 2 (11%) stable disease, whereas 2 showed disease progression. The -1154A/G VEGF polymorphism, plasma VEGF, and bFGF after the first cycle of chemotherapy may represent useful pharmacodynamic markers to predict better outcomes.
The combination of docetaxel and oral metronomic chemotherapy is effective and well tolerated in mCRPC patients and may deserve further evaluation.
多西他赛联合泼尼松目前是转移性去势抵抗性前列腺癌（mCRPC）的标准一线治疗方法。本研究旨在评估多西他赛联合泼尼松与环磷酰胺节拍化疗治疗 mCRPC 患者的临床疗效和药效学/药效遗传学特征。
41 例初治的化疗患者接受多西他赛（60 mg/m2 静脉滴注，每 3 周 1 次，最多 12 个周期），从第 2 天开始，同时口服泼尼松 10 mg/天、塞来昔布 400 mg/天和环磷酰胺节拍化疗 50 mg/天。采用 ELISA 法检测血浆 VEGF 和 bFGF。采用 ABI PRISM 7900HT SDS 和 TaqMan SNP 基因分型实时 PCR-SNP 分析 VEGF 基因。
87%的患者在 6 个月时无疾病进展。39 例可评估患者中有 82%（39 例中有 32 例）的前列腺特异性抗原下降≥50%，中位无进展生存期为 12.3 个月。3 级不良事件为中性粒细胞减少（5%）、血小板减少、腹泻和口腔炎（2.5%）。中位 PFS 和 OS 分别为 14.9 个月（95%CI，9.2-15.3 个月）和 33.3 个月（95%CI，23-35.6 个月）。11 例（28%）可评估疾病的患者中，5 例（44%）达到完全缓解，2 例（11%）部分缓解，2 例（11%）稳定，2 例疾病进展。化疗第 1 周期后的-1154A/G VEGF 多态性、血浆 VEGF 和 bFGF 可能是预测更好结局的有用药效学标志物。
多西他赛联合口服节拍化疗在 mCRPC 患者中具有疗效且耐受性良好，值得进一步评估。
