DOI: 10.1200/jco.2000.18.6.1351. Tirapazamine Plus Cisplatin Versus Cisplatin in Advanced Non–Small-Cell Lung Cancer: A Report of the International CATAPULT I Study Group [Penn]

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

10.1200/jco.2000.18.6.1351

Crossref journal-article

American Society of Clinical Oncology (ASCO)

Journal of Clinical Oncology (233)

Abstract

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.

Bibliography

von Pawel, J., von Roemeling, R., Gatzemeier, U., Boyer, M., Elisson, L. O., Clark, P., Talbot, D., Rey, A., Butler, T. W., Hirsh, V., Olver, I., Bergman, B., Ayoub, J., Richardson, G., Dunlop, D., Arcenas, A., Vescio, R., Viallet, J., & Treat, J. (2000). Tirapazamine Plus Cisplatin Versus Cisplatin in Advanced NonâSmall-Cell Lung Cancer: A Report of the International CATAPULT I Study Group. Journal of Clinical Oncology, 18(6), 1351â1359.

Authors 19

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

References 26 Referenced 224

10.3322/canjclin.48.1.6
Perrone F, Rossi A, Ianniello GP, et al: Vinorelbine (VNR) plus best supportive care (BSC) vs BSC in the treatment of advanced non-small cell lung cancer (NSCLC) elderly patients (PTS): Results of a phase III randomized trial. Proc Am Soc Clin Oncol 17:455a,1998 (abstr 1752)
Fossella FV, Lee JS, Hong WK: Management strategies for recurrent non-small cell lung cancer. Semin Oncol 24:455,1997-462,
Sandler A, Nemunaitis J, Dehnam C, et al: Phase III study of cisplatin (C) with or without gemcitabine (G) in patients with advanced non-small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 17:454a,1998 (abstr 1747)
10.1200/JCO.1998.16.7.2459
Gatzemeier U, von Pawel J, Gottfried M, et al: Phase III comparative study of high-dose cisplatin (HD-CIS) versus a combination of paclitaxel (TAX) and cisplatin (CIS) in patients with advanced non-small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 17:454a,1998 (abstr 1748)
Belani CP, Natale RB, Lee JS, et al: Randomized phase III trial comparing cisplatin/etoposide versus carboplatin/paclitaxel in advanced and metastatic non-small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 17:455a,1998 (abstr 1751)
Crino L, Conte P, DeMarinus F, et al: A randomised trial of gemcitabine cisplatin (GP) versus mitomycin, ifosamide and cisplatin (MIC) in advanced non-small cell lung cancer (NSCLC): A multicenter phase III study. Proc Am Soc Clin Oncol 17:455a,1998 (abstr 1750)
10.1200/JCO.1990.8.9.1556
10.1016/0167-8140(88)90225-3
10.1038/bjc.1955.55
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Dorie MJ, Brown JM: Tumor-specific, schedule-dependent interaction between tirapazamine (SR 4233) and cisplatin. Cancer Res 53:4633,1993-4636,
Senan S, Rampling R, Graham MA, et al: Phase I and pharmacokinetic study of tirapazamine (SR4233) administered every three weeks. Clin Cancer Res 3:31,1997-38,
Rodriguez GI, Valdivieso M, Von Hoff DD, et al: A phase I/II trial of the combination of tirapazamine and cisplatin in patients with non-small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 15:382,1996 (abstr 1144)
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Treat J, Rodriguez G, Miller V, et al: An integrated phase I/II analysis of Tirazone™ (tirapazamine) + cisplatin: Safety and efficacy in advanced non-small cell lung cancer (NSCLC) patients. Proc Am Soc Clin Oncol 17:472a,1998 (abstr 1815)
Brown JM, Giaccia AJ: The unique physiology of solid tumors: Opportunities (and problems) for cancer therapy. Cancer Res 58:1408,1998-1416,
Kennedy KA: Hypoxic cells as specific drug targets for chemotherapy. Anticancer Drug Des 2:181,1987-194,
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Gatineau M, Rixe O, Fizazi K, et al: Phase I study of tirapazamine-cisplatin-vinorelbine in patients with inoperable non small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 17:485a,1998 (abstr 1865)
Ng K, Treat J, O’Dwyer P, et al: A phase I trial of the addition of paclitaxel to tirapazamine (TPZ) and cisplatin in patients with advanced non-small cell lung cancer. Proc Am Soc Clin Oncol 17:496a,1998 (abstr 1910)
Curran WJ, Movsas B, Hancock S, et al: Phase I trial of oral Tirazone™ (tirapazamine, TPZ) shows good bioavailability and tolerance. Proc Am Soc Clin Oncol 17:208a,1998 (abstr 802)

Dates

Type	When
Created	8 years, 6 months ago (Feb. 24, 2017, 2:16 a.m.)
Deposited	3 years, 3 months ago (May 25, 2022, 5:43 p.m.)
Indexed	1 week, 3 days ago (Aug. 21, 2025, 1:57 p.m.)
Issued	25 years, 5 months ago (March 13, 2000)
Published	25 years, 5 months ago (March 13, 2000)
Published Print	25 years, 5 months ago (March 13, 2000)

Funders 0

None

BibTeX

@article{von_Pawel_2000, title={Tirapazamine Plus Cisplatin Versus Cisplatin in Advanced Non–Small-Cell Lung Cancer: A Report of the International CATAPULT I Study Group}, volume={18}, ISSN={1527-7755}, url={http://dx.doi.org/10.1200/jco.2000.18.6.1351}, DOI={10.1200/jco.2000.18.6.1351}, number={6}, journal={Journal of Clinical Oncology}, publisher={American Society of Clinical Oncology (ASCO)}, author={von Pawel, Joachim and von Roemeling, Reinhard and Gatzemeier, Ulrich and Boyer, Michael and Elisson, Lars Ove and Clark, Peter and Talbot, Denis and Rey, Augustin and Butler, Thomas W. and Hirsh, Vera and Olver, Ian and Bergman, Bengt and Ayoub, Joseph and Richardson, Gary and Dunlop, David and Arcenas, Anthony and Vescio, Robert and Viallet, Jean and Treat, Joseph}, year={2000}, month=mar, pages={1351–1359} }

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