Multinational, Double-Blind, Phase III Study of Prednisone and Either Satraplatin or Placebo in Patients With Castrate-Refractory Prostate Cancer Progressing After Prior Chemotherapy: The SPARC Trial
Multinational, Double-Blind, Phase III Study of Prednisone and Either Satraplatin or Placebo in Patients With Castrate-Refractory Prostate Cancer Progressing After Prior Chemotherapy: The SPARC Trial
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DOI：
10.1200/jco.2008.20.1228
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发表时间：
2009-11-10
影响因子：
45.3
通讯作者：
Rozencweig, Marcel
中科院分区：
文献类型：
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作者：
Sternberg, Cora N.;Petrylak, Daniel P.;Rozencweig, Marcel
目的这项多国、双盲、随机、安慰剂对照的 III 期试验评估了口服铂类似物沙铂对既往化疗方案后进展的转移性去势难治性前列腺癌 (CRPC) 患者的疗效和耐受性。患者和方法 950 名患者被随机分配 (2:1)，在治疗的第 1 至 5 天接受口服沙铂 (n = 635) 80 mg/m(2)。 35 天周期和泼尼松 5 mg 每天两次，或安慰剂 (n = 315) 和泼尼松 5 mg 每天两次。主要终点是无进展生存期和总生存期（OS）。次要终点是疼痛进展时间 (TPP)。 结果 与安慰剂相比，沙铂组的进展或死亡风险降低了 33%（风险比 [HR] = 0.67；95% CI，0.57 至 0.77；P < .001）。无论先前进行多西紫杉醇治疗，该效果均得以维持。沙铂组和安慰剂组的 OS 没有差异（HR = 0.98；95% CI，0.84 至 1.15；P = .80）。与安慰剂相比，沙铂显着降低 TPP（HR = 0.64；95% CI，0.51 至 0.79；P < .001）。尽管沙铂更容易发生骨髓抑制和胃肠道疾病，但沙铂通常具有良好的耐受性。 结论 对于初次化疗后出现进展的转移性 CRPC 患者，口服沙铂可延缓疾病进展和疼痛，但没有提供显着的 OS 获益。沙铂通常耐受性良好。这些结果表明沙铂对于初次化疗后病情进展的 CRPC 患者具有活性。
PurposeThis multinational, double-blind, randomized, placebo-controlled, phase III trial assessed the efficacy and tolerability of the oral platinum analog satraplatin in patients with metastatic castrate-refractory prostate cancer (CRPC) experiencing progression after one prior chemotherapy regimen.Patients and MethodsNine hundred fifty patients were randomly assigned (2:1) to receive oral satraplatin (n = 635) 80 mg/m(2) on days 1 to 5 of a 35-day cycle and prednisone 5 mg twice daily or placebo (n = 315) and prednisone 5 mg twice daily. Primary end points were progression- free survival and overall survival (OS). The secondary end point was time to pain progression (TPP).ResultsA 33% reduction (hazard ratio [HR] = 0.67; 95% CI, 0.57 to 0.77; P < .001) was observed in the risk of progression or death with satraplatin versus placebo. This effect was maintained irrespective of prior docetaxel treatment. No difference in OS was seen between the satraplatin and placebo arms (HR = 0.98; 95% CI, 0.84 to 1.15; P = .80). Compared with placebo, satraplatin significantly reduced TPP (HR = 0.64; 95% CI, 0.51 to 0.79; P < .001). Satraplatin was generally well tolerated, although myelosuppression and GI disorders occurred more frequently with satraplatin.ConclusionOral satraplatin delayed progression of disease and pain in patients with metastatic CRPC experiencing progression after initial chemotherapy but did not provide a significant OS benefit. Satraplatin was generally well tolerated. These results suggest activity for satraplatin in patients with CRPC who experience progression after initial chemotherapy.