Phase II study of the combination of the novel bioreductive agent, tirapazamine, with cisplatin in patients with advanced non-small-cell lung cancer.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Miller
V A
VA
Department of Medicine, Memorial Sloan-Kettering Cancer Center, Cornell University Medical College, NY, USA. millerv@mskcc.org
Ng
K K
KK
Grant
S C
SC
Kindler
H
H
Pizzo
B
B
Heelan
R T
RT
von Roemeling
R
R
Kris
M G
MG
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D004357:Drug Synergism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D000077704:Tirapazamine; D016896:Treatment Outcome; D014227:Triazines / Q000008:administration & dosage
D014227:Triazines; D000077704:Tirapazamine; D002945:Cisplatin