MITOMYCIN-C AND MENADIONE FOR THE TREATMENT OF LUNG-CANCER - A PHASE-II TRIAL

被引:48
作者
TETEF, M [1 ]
MARGOLIN, K [1 ]
AHN, C [1 ]
AKMAN, S [1 ]
CHOW, W [1 ]
LEONG, L [1 ]
MORGAN, RJ [1 ]
RASCHKO, J [1 ]
SOMLO, G [1 ]
DOROSHOW, JH [1 ]
机构
[1] CITY HOPE NATL MED CTR, DEPT BIOSTAT, DUARTE, CA 91010 USA
关键词
D O I
10.1007/BF00872865
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
A phase II trial of menadione [2.5 gm/m(2) as a continuous intravenous (iv) infusion over 48 hours] followed by mitomycin C (10-20 mg/m(2) iv 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 regressions 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.
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页码:157 / 162
页数:6
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