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Journal of Clinical Oncology, Vol 18, Issue 6 (March), 2000: 1351-1359
© 2000 American Society for Clinical Oncology

Tirapazamine Plus Cisplatin Versus Cisplatin in Advanced Non–Small-Cell Lung Cancer: A Report of the International CATAPULT I Study Group

By Joachim von Pawel, Reinhard von Roemeling, Ulrich Gatzemeier, Michael Boyer, Lars Ove Elisson, Peter Clark, Denis Talbot, Augustin Rey, Thomas W. Butler, Vera Hirsh, Ian Olver, Bengt Bergman, Joseph Ayoub, Gary Richardson, David Dunlop, Anthony Arcenas, Robert Vescio, Jean Viallet, Joseph Treat

From the Asklepios Fachkliniken München-Gauting, Gauting, and Hospital Grosshansdorf, Hamburg, Germany; Sanofi Research, Malvern, and University of Pennsylvania Medical Center, Philadelphia, PA; Royal Prince Alfred Hospital, Camperdown, New South Wales, Royal Adelaide Hospital, Adelaide, South Australia, and Monash Medical Centre, Clayton, Victoria, Australia; University Hospital, Malmö, and Sahlgrenska University Hospital, Gothenburg, Sweden; Clatterbridge Centre for Oncology, Merseyside, Churchill Hospital, Oxford, and Glasgow Royal Infirmary, Glasgow, United Kingdom; Sanofi Recherche, Gentilly Cedex, France; The Clarksville Regional Hematology-Oncology Group, Clarksville, TN; Royal Victoria Hospital and Hospital Notre Dame, Montreal, Quebec, Canada; Washington DC Veterans Affairs Medical Center, Washington, DC; and Veterans Affairs Medical Center–West Los Angeles, Los Angeles, CA.

Address reprint requests to Joachim von Pawel, MD, Leiter der Abteilung Onkologie, Asklepios-klinik, Robert-Koch-Allee 2, Gauting, Germany D82131.

PURPOSE: 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).

PATIENTS AND METHODS: Patients with previously untreated NSCLC were randomized to receive either tirapazamine (390 mg/m2 infused over 2 hours) followed 1 hour later by cisplatin (75 mg/m2 over 1 hour) or 75 mg/m2 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.

CONCLUSION: 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.




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