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Gemcitabin/Cisplatin vs. MVAC

5-Jahres-Ergebnisse der Phase-III-Studie zur Chemotherapie des fortgeschrittenen Urothelkarzinoms in Deutschland

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Zusammenfassung

Von insgesamt 405 Patienten einer internationalen prospektiv randomisierten Phase-III-Studie zur systemischen Chemotherapie des fortgeschrittenen Urothelkarzinoms [maximal 6 Zyklen Gemcitabin/Cisplatin (GC) vs. Methotrexat/Vinblastin/Adriamycin/Cisplatin (MVAC)] wurden 70 Patienten aus bundesdeutschen uroonkologischen Zentren rekrutiert. Zu diesen Patienten, die innerhalb der "Arbeitsgemeinschaft Urologische Onkologie" empfohlenen Studie AB 12/96 rekrutiert wurden, wird über das 5-Jahres-Langzeitüberleben sowie über therapierelevante Daten berichtet. Die Tumorremissionsraten (GC=54%, MVAC=53%) sowie die 5-Jahres-Gesamtüberlebensrate (GC=10%, MVAC=18%), die tumorspezifische Überlebensrate (GC=14%, MVAC=22%) und die progressionsfreie Überlebensrate (GC=13%, MVAC=7%) waren in den beiden Behandlungsarmen nicht signifikant unterschiedlich.

Die Anzahl von Patienten mit hämatologischer Grad-III/IV-Toxizität (Anämie und Thrombopenie) war signifikant größer im Gemcitabin/Cisplatin-Behandlungsarm (Anämie Grad III/IV, GC=52%, MVAC=20% und Thrombopenie Grad III/IV, GC=54%, MVAC=17%) mit einer signifikant höheren Transfusionsrate für Erythrozytenkonzentrate im GC-Arm. Neutro- bzw. leukopenisches Fieber trat nur unter der MVAC-Therapie bei 3 Patienten auf. Die zum Zeitpunkt der Auswertung noch lebenden Patienten zeichnen sich vorwiegend durch ein lokal fortgeschrittenes Tumorstadium bzw. in Einzelfällen durch eine lymphatische bzw. solitäre Metastasierung aus. Von Patienten mit viszeralen Metastasen lebt nach 30 Monaten Beobachtungszeit keiner mehr.

Abstract

Of 405 patients with stage IV transitional cell carcinoma from an international multicenter phase III trial, 70 were randomized in Germany to receive either gemcitabine/cisplatin or standard MVAC systemic chemotherapy for locally advanced or metastatic urothelial cancer. Overall survival as the primary endpoint of the study was similar in both arms (median survival GC 15.4 months vs MVAC 16.1 months), as were tumor-specific survival and time to progressive disease. In the intent-to-treat analysis, the 5-year overall survival rate was 10% for patients randomized to GC and 18% randomized to MVAC. Tumor overall response rates (GC 54%, MVAC 53%) were similar. The toxic death rate was 0% in the GC arm and 3% (one patient) in the MVAC arm. Significantly more GC than MVAC patients experienced grade 3/4 anemia (GC 52%, MVAC 20%) with significantly more red blood cell transfusions in the GC arm.

Significantly more GC than MVAC patients had grade 3/4 thrombocytopenia (GC 54%, MVAC 17%) without grade 3/4 hemorrhage or hematuria in either arm. More MVAC patients experienced grade 3/4 neutropenia (GC 56%, MVAC 61%, p=1.000), neutropenic or leukopenic fever (GC 0%, MVAC 10%, p=0.237), mucositis (GC 0%, MVAC 7%, p=0.495), and alopecia (GC 6%, MVAC 36%, p=0.004). GC represents a reasonable alternative for the palliative treatment of patients with locally advanced and metastatic transitional cell carcinoma. Sustained long-term survival was only found for patients with locally advanced cancer, lymphatic metastases, or solitary distant metastasis but not for visceral metastatic disease.

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Danksagung

Besonderer Dank gilt Herrn Dr. Adalbert Lackhoff, Herrn Dr. Johannes Blatter (Fa. Lilly Deutschland GmbH, Bad Homburg) für die Vermittlung des Kontaktes zur "Data Management" Abteilung der Eli Lilly-Firmenzentrale in Indianapolis. Weiterhin bedanken sich die Autoren bei Frau Ginger Shoup und Frau Cathy Taylor (Data Management, Eli Lilly and Company, Indianapolis, USA) für die Bereitstellung der Patienten bezogenen Einzeldaten.

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Authors and Affiliations

  1. Studiengruppe AB 12/96 der Arbeitsgemeinschaft Urologische Onkologie (AUO)

    J. Lehmann, M. Retz, G. Steiner, P. Albers, E. Jaeger, A. Knuth, C. Lippert, M. Koser, K. Stockamp, C. Otto, H. Melchior, C. Faßmann, C. Potratz, T. Loch, H. G. Derigs, T. Becker, T. Kälble, H.-J. Piechota, L. Hertle, S. Weinknecht, L. Weißbach, M. Al-Mwalad, A. Hamza, H. Henß, D. Brkovic, S. Pomer, J. Roloff, P. Walz, R. Muschter, U. Tunn, E. Winter, P. Bub, U. Kaldenbach, S. Roth, A. Brauers, G. Jakse, A. E. Richter, M. Wirth, J. Hartlapp, H. van Ahlen & M. Stöckle

  2. Klinik für Urologie und Kinderurologie, Universität des Saarlandes, 66421, Homburg/Saar

    J. Lehmann

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  1. J. Lehmann
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  2. M. Retz
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  3. G. Steiner
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  4. P. Albers
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  7. C. Lippert
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  12. C. Faßmann
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  14. T. Loch
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  15. H. G. Derigs
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  16. T. Becker
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  17. T. Kälble
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  18. H.-J. Piechota
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  19. L. Hertle
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  20. S. Weinknecht
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  21. L. Weißbach
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  22. M. Al-Mwalad
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  23. A. Hamza
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  24. H. Henß
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  25. D. Brkovic
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  26. S. Pomer
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  27. J. Roloff
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  28. P. Walz
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  29. R. Muschter
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  30. U. Tunn
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  31. E. Winter
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  32. P. Bub
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  33. U. Kaldenbach
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  34. S. Roth
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  35. A. Brauers
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  36. G. Jakse
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  37. A. E. Richter
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  40. H. van Ahlen
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  41. M. Stöckle
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Corresponding author

Correspondence to J. Lehmann.

Appendix

Appendix

J.L., M.R., M.S. (Klinik für Urologie und Kinderurologie, Universität des Saarlandes, Homburg/Saar); G.S., P.A. (Klinik für Urologie, Rheinische-Friedrich-Wilhelms-Universität, Bonn); E.J., A.K. (II. Medizinische Klinik Klinik für Urologie, Krankenhaus Nordwest, Frankfurt am Main); C.L. (Klinik für Urologie, Krankenhaus Nordwest, Frankfurt am Main und Urologische Klinik, Klinikum der Stadt Ludwigshafen/Rhein); M.K., K.S. (Urologische Klinik, Klinikum der Stadt Ludwigshafen/Rhein); C.O., H.M. (Klinik für Urologie, Städtische Kliniken Kassel); C.F., C.P., T.L. (Klinik für Urologie, Christian-Albrechts-Universität, Kiel), H.D. (III. Med. Klinik, Hämatologie, Klinikum der Johannes-Gutenberg-Universität, Mainz), T.B., T.K. (Klinik für Urologie, Klinikum der Philipps-Universität, Marburg/Lahn); H.-J.P., L.H. (Klinik für Urologie, Med. Einrichtungen der Westfälischen Wilhelms-Universität, Münster); S.W., L.W. (Urologische Abteilung, Krankenhaus am Urban, Berlin); M.A.-M., A.H. (Klinik für Urologie, Medizinische Fakultät der Martin-Luther-Universität zu Halle-Wittenberg); H.H. (Innere Medizin I, Hämatologie/Onkologie, Klinikum der Albert-Ludwigs-Universität, Freiburg); D.B., S.P. (Klinik für Urologie, Klinikum der Ruprecht-Karls-Universität Heidelberg); J.R., P.W. (Klinik für Urologie, Klinikum Lüdenscheid); R.M. (Klinik für Urologie, Klinikum Großhadern der Ludwig-Maximilians-Universität, München); U.T. (Urologische Klinik, Städtische Kliniken Offenbach); E.W., P.B. (Urologische Klinik, Klinikum Schwerin); U.K., S.R. (Klinik für Urologie und Kinderurologie, Klinikum Wuppertal GmbH); A.B., G.J. (Klinik für Urologie, Med. Einrichtungen der RWTH Aachen); A.R., M.W. (Klinik für Urologie, Carl-Gustav-Carus-Universität, Dresden); J.H. (Abteilung Hämato-Onkologie, Städtische Kliniken, Osnabrück); H.v.A. (Klinik für Urologie, Städtische Kliniken, Osnabrück)

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Lehmann, J., Retz, M., Steiner, G. et al. Gemcitabin/Cisplatin vs. MVAC. Urologe [A] 42, 1074–1086 (2003). https://doi.org/10.1007/s00120-003-0317-4

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