Miller V A, Ng K K, Grant S C, Kindler H, Pizzo B, Heelan R T, von Roemeling R, Kris M G
Department of Medicine, Memorial Sloan-Kettering Cancer Center, Cornell University Medical College, NY, USA.
Ann Oncol. 1997 Dec;8(12):1269-71. doi: 10.1023/a:1008219125746.
Tirapazamine is a bioreductive compound synergistic with cisplatin in preclinical testing. This phase II study was conducted to evaluate the efficacy and toxicity of tirapazamine with cisplatin in patients with advanced non-small-cell lung cancer.
Twenty patients with unresectable stage III-B and IV non-small-cell lung cancer who had not received prior chemotherapy were given tirapazamine (390 mg/m2) intravenously (i.v.) over two hours followed one hour later by cisplatin (75 mg/m2) i.v. over one hour every 21 days.
Five of 20 patients (25%) had major objective responses (95% confidence interval, 11%-50%). Median duration of response was eight months with a one-year survival of 40%. Toxicities included temporary hearing loss (25%), muscle cramping, diarrhea, skin rash and nausea/vomiting. No grade 3 or 4 hematologic or renal toxicity was observed.
The combination of tirapazamine plus cisplatin appears to be safe and active in the treatment of advanced non-small lung cancer without a substantial increase in toxicity compared to cisplatin alone. A phase III randomized study compared the combination to cisplatin alone has completed accrual. Further evaluation of tirapazamine with other active agents and in multi-modality therapy is warranted.
替拉扎明是一种在临床前试验中与顺铂具有协同作用的生物还原化合物。本II期研究旨在评估替拉扎明联合顺铂治疗晚期非小细胞肺癌患者的疗效和毒性。
20例未经治的不可切除的III - B期和IV期非小细胞肺癌患者，每21天接受一次静脉滴注，先静脉滴注替拉扎明（390mg/m²）2小时，1小时后再静脉滴注顺铂（75mg/m²）1小时。
20例患者中有5例（25%）出现主要客观缓解（95%置信区间，11% - 50%）。中位缓解持续时间为8个月，1年生存率为40%。毒性包括暂时性听力丧失（25%）、肌肉痉挛、腹泻、皮疹和恶心/呕吐。未观察到3级或4级血液学或肾脏毒性。
与单独使用顺铂相比，替拉扎明联合顺铂在治疗晚期非小细胞肺癌中似乎安全有效，且毒性没有显著增加。一项将该联合方案与单独使用顺铂进行比较的III期随机研究已完成入组。有必要进一步评估替拉扎明与其他活性药物联合以及在多模式治疗中的效果。
