Tirapazamine plus cisplatin versus cisplatin in advanced non-small-cell lung cancer: A report of the international CATAPULT I study group. Cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors.
OBJECTIVE
A phase III trial, Cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors (CATAPULT I), was designed to determine the efficacy and safety of tirapazamine plus cisplatin for the treatment of non-small-cell lung cancer (NSCLC).


METHODS
Patients with previously untreated NSCLC were randomized to receive either tirapazamine (390 mg/m(2) infused over 2 hours) followed 1 hour later by cisplatin (75 mg/m(2) over 1 hour) or 75 mg/m(2) of cisplatin alone, every 3 weeks for a maximum of eight cycles.


RESULTS
A total of 446 patients with NSCLC (17% with stage IIIB disease and pleural effusions; 83% with stage IV disease) were entered onto the study. Karnofsky performance status (KPS) was >/= 60 for all patients (for 10%, KPS = 60; for 90%, KPS = 70 to 100). Sixty patients (14%) had clinically stable brain metastases. The median survival was significantly longer (34.6 v 27. 7 weeks; P =.0078) and the response rate was significantly greater (27.5% v 13.7%; P <.001) for patients who received tirapazamine plus cisplatin (n = 218) than for those who received cisplatin alone (n = 219). The tirapazamine-plus-cisplatin regimen was associated with mild to moderate adverse events, including acute, reversible hearing loss, reversible, intermittent muscle cramping, diarrhea, skin rash, nausea, and vomiting. There were no incremental increases in myelosuppression, peripheral neuropathy, or renal, hepatic, or cardiac toxicity and no deaths related to tirapazamine.


CONCLUSIONS
The CATAPULT I study shows that tirapazamine enhances the activity of cisplatin in patients with advanced NSCLC and confirms that hypoxia is an exploitable therapeutic target in human malignancies.
von Pawel
J
J
Asklepios Fachkliniken München-Gauting, Gauting, and Hospital Grosshansdorf, Hamburg, Germany.
von Roemeling
R
R
Gatzemeier
U
U
Boyer
M
M
Elisson
L O
LO
Clark
P
P
Talbot
D
D
Rey
A
A
Butler
T W
TW
Hirsh
V
V
Olver
I
I
Bergman
B
B
Ayoub
J
J
Richardson
G
G
Dunlop
D
D
Arcenas
A
A
Vescio
R
R
Viallet
J
J
Treat
J
J
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary; D015687:Cell Hypoxia; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D000077704:Tirapazamine; D014227:Triazines / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D014227:Triazines; D000077704:Tirapazamine; D002945:Cisplatin