Tetef M, Margolin K, Ahn C, Akman S, Chow W, Leong L, Morgan R J, Raschko J, Somlo G, Doroshow J H
Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA.
Invest New Drugs. 1995;13(2):157-62. doi: 10.1007/BF00872865.
A phase II trial of menadione [2.5 gm/m2 as a continuous intravenous (i.v.) infusion over 48 hours] followed by mitomycin C (10-20 mg/m2 i.v. bolus) administered every 4 to 6 weeks was performed in 23 patients with advanced lung cancer. Menadione, a vitamin K analog which lowers intracellular pools of reduced glutathione (GSH), was combined with mitomycin C in an attempt to overcome thiol-mediated resistance to alkylating agent chemotherapy. The median age of patients entered on this trial was 62 years; performance status ranged from 60-90%. Two of the 23 patients (9%; 95% confidence interval, 1% to 28%) had objective responses lasting 3.5 months and 13 months respectively, while 4 additional patients developed short unconfirmed responses (lacking follow-up response data to estimate response duration). Median survival for all patients was 5.5 months. Treatment with mitomycin C and menadione was well tolerated except for hematologic toxicity and cardiac events of unclear relationship to the study drugs. Thirty-one percent of treatment courses were complicated by grade 3 or 4 hematologic toxicity including one episode of hemolytic anemia. One patient developed interstitial pneumonitis. Two patients developed a decrease in left ventricular ejection fraction: one patient remained asymptomatic, but the other patient developed congestive heart failure. Although only 9% of patients had confirmed objective responses, 28% (5 of 18) of the patients with non-small cell lung cancer demonstrated biological activity (tumor regression fulfilling the criteria for objective response on a single occasion but 3 patients lacking a follow-up measurement to document response duration) to this combination of mitomycin C and menadione. We conclude that further studies of chemomodulation in non-small cell lung cancer are appropriate.
对23例晚期肺癌患者进行了一项II期试验，先静脉持续输注维生素K3（2.5 g/m²，持续48小时），随后每4至6周静脉推注丝裂霉素C（10 - 20 mg/m²）。维生素K3是一种维生素K类似物，可降低细胞内还原型谷胱甘肽（GSH）水平，将其与丝裂霉素C联合使用，试图克服硫醇介导的对烷化剂化疗的耐药性。参与该试验患者的中位年龄为62岁；体能状态评分在60%至90%之间。23例患者中有2例（9%；95%置信区间为1%至28%）出现客观缓解，缓解期分别为3.5个月和13个月，另有4例患者出现短暂的未确认缓解（缺乏随访反应数据以估计反应持续时间）。所有患者的中位生存期为5.5个月。除血液学毒性和与研究药物关系不明的心脏事件外，丝裂霉素C和维生素K3治疗耐受性良好。31%的疗程出现3级或4级血液学毒性并发症，包括1例溶血性贫血。1例患者发生间质性肺炎。2例患者左心室射血分数下降：1例患者无症状，但另1例患者发生充血性心力衰竭。尽管只有9%的患者有确认的客观缓解，但28%（18例中的5例）非小细胞肺癌患者对丝裂霉素C和维生素K3的这种联合治疗表现出生物学活性（肿瘤退缩在单次符合客观缓解标准，但3例患者缺乏随访测量以记录反应持续时间）。我们得出结论，对非小细胞肺癌进行进一步的化学调节研究是合适的。
