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Pneumologie 2004; 58(12): 845-849
DOI: 10.1055/s-2004-830056
Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Tirapazamine, Cisplatin und Gemcitabine beim fortgeschrittenen nichtkleinzelligen Bronchialkarzinom - eine Phase II-Studie

Phase II-Trial of Tirapazamine in Combination with Cisplatin and Gemcitabine in Patients with Advanced Non-Small-Cell-Lung-Cancer (NSCLC)M.  Reck1 , J.  von Pawel2 , C.  Nimmermann2 , G.  Groth1 , U.  Gatzemeier1
  • 1Onkologischer Schwerpunkt, Krankenhaus Großhansdorf, Großhansdorf (Leitung: Dr. U. Gatzemeier)
  • 2Onkologische Abteilung, Asklepios Kliniken Gauting, München (Leitung: Dr. von Pawel)
Diese Studie wurde unterstützt von der Firma Sanofi Synthelabo Deutschland.DanksagungFür die Erstellung des Manuskriptes danken wir Fr. Waltraud Krumm.
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Publication History

Eingang: 13. Juli 2004

Annahme: 4. August 2004

Publication Date:
14 December 2004 (online)

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Zusammenfassung

Trotz Fortschritte in der Chemotherapie des fortgeschrittenen und metastasierten nichtkleinzelligen Bronchialkarzinoms (NSCLC) ist die Prognose mit einer 5-Jahres-Überlebensrate von 2 - 5 % denkbar schlecht. Aufgrund des hohen Anteils von hypoxischen Zellen in soliden Tumoren bietet der Einsatz von Substanzen mit Wirksamkeit im hypoxischen Milieu wie dem Benzotriazinderivat Tirapazamine (SR 259 075) eine Möglichkeit, die Resultate zu verbessern. Wir behandelten 45 Patienten mit einem fortgeschrittenen oder metastasierten nichtkleinzelligen Bronchialkarzinom (Stadium IIIb: 20 Patienten), (Stadium IV: 25 Patienten) mit der Kombination Tirapazamine 330 mg/m2 (Tag 1), Cisplatin 75 mg/m2 (Tag 1), Gemcitabine 1250 mg/m2 (Tag 1 und 8) alle 3 Wochen. Bei einer Ansprechrate von 40 % beobachteten wir ein medianes progressionsfreies Überleben von 6,7 Monaten (4,8 - 8,1 Monate) und ein medianes Überleben von 8,1 Monaten (7,5 - 12,5 Monate) mit einer 1-Jahres-Überlebensrate von 35 %. Die hämatologische und nicht-hämatologische Toxizität war moderat (Neutropenie CTC Grad 3 und 4: 20 %, Thrombopenie CTC Grad 3 und 4: 16 %, Übelkeit und Erbrechen CTC Grad 3: 5 %). Die Kombination von Cisplatin/Gemcitabine mit Tirapazamine war gut durchführbar und zeigte vergleichbare Ergebnisse zur kombinierten Chemotherapie beim NSCLC. Die Ergebnisse einer anschließenden Phase III-Studie zur Bewertung des Stellenwertes des Tirapazamine stehen aus.

Abstract

Despite improvements in chemotherapy of advanced and metastatic Non-Small-Cell-Lung-Cancer (NSCLC) the prognosis of these patients still remains poor with a 5-year-survival of 2 to 5 %. Due to the high level of hypoxic cells in solid tumors agents with activity in hypoxic milieu as the Benzotriazine compound Tirapazamine (SR 259 075) might improve the therapeutic results. We treated 45 patients with advanced or metastatic Non-Small-Cell-Lung-Cancer (stage IIIb: 20 patients, stage IV: 25 patients) with the combination TPZ 330 mg/m2 (day 1), Cisplatin 75 mg/m2 (day 1) and Gemcitabine 1250 mg/m2 (day 1 and 8) every 3 weeks. With a response rate of 40 % median progression free survival was 6.7 months (4.8 - 8.1 months) and median survival was 8.1 months (7.5 - 12.5 months), (1-year-survival: 35 %). Hematologic and non-hematologic toxicity was moderate (neutropenia CTC grade 3 and 4: 20 %, thrombocytopenia CTC grade 3 and 4: 16 %, nausea and vomiting CTC 3: 5 %). Treatment of advanced and metastatic NSCLC with TPZ in combination with Gemcitabine/Cisplatin was well feasible and showed results recording to currently published data. The results of a following phase III-trial are awaited.

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Dr. Martin Reck

Onkologischer Schwerpunkt, Krankenhaus Großhansdorf

Wöhrendamm 80

22927 Großhansdorf

Email: dr.martin.reck@web.de

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