Mitomycin C and menadione for the treatment of lung cancer: a phase II trial.
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.
Tetef
M
M
Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA.
Margolin
K
K
Ahn
C
C
Akman
S
S
Chow
W
W
Leong
L
L
Morgan
R J
RJ
Raschko
J
J
Somlo
G
G
Doroshow
J H
JH
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000401:mortality; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000401:mortality; D004347:Drug Interactions; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014812:Vitamin K / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; D015507:Drugs, Investigational; D014812:Vitamin K; D016685:Mitomycin