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Behandlung lokoregionär fortgeschrittener nichtkleinzelliger Bronchialkarzinome im Stadium IIIB mit Bestrahlung und Interferon β

Treatment of locally advanced non-small cell lung cancer, stage IIIB with irradiation and interferon β: Preliminary results of a phase II study

Vorläufige Ergebnisse einer Phase-II-Studie

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Zusammenfassung

Hintergrund

Sowohl In-vitro- als auch In-vivo-Studien zeigten eine strahlensensibilisierende Wirkung von Interferon β bei Malignomen und auch gleichzeitig eine radioprotektive Wirkung im normalen Lungengewebe. Es wurde deshalb eine Phase-II-Studie eingeleitet, um den Effekt der Kombinationsbehandlung aus Bestrahlung und Interferon β bei Patienten mit fortgeschrittenen nichtkleinzelligen Bronchialkarzinomen zu überprüfen.

Patienten und Methode

Von Februar 1994 bis November 1996 wurden 14 Patienten mit nichtkleinzelligen Bronchial-karzinomen im Stadium IIIB im Rahmen dieser Studie behandelt. Es erfolgte eine lokoregionäre Bestrahlung bis 59,4 Gy mit Einzeldosen von 1,8 Gy pro Tag bei fünf Fraktionen in der Woche. Während der ersten, dritten und fünften Behandlungswoche erhielten die Patienten unmittelbar vor der Bestrahlung an jeweils drei aufeinanderfolgenden Tagen täglich 5 Millionen Einheiten Interferon β (Fiblaferon®) intravenös.

Ergebnisse

Bei vier der 14 Patienten (28,6%) kam es zu einer kompletten Remission und bei sieben Patienten (50%) zu einer partiellen Remission, so daß die Ansprechrate insgesamt 78,6% betrug. Bei einer mittleren Nachbeobachtungszeit von 23,3 Monaten belief sich die Überlebensrate nach einem, zwei und drei Jahren auf 56,3%, 37,5% und 37,5%. Das mediane Überleben betrug 13 Monate. Drei der 14 Patienten (21,4%) erfuhren insgesamt sieben Grad-3-Akutnebenwirkungen, bei zwei Patienten (14,3%) kam es jeweils zu einer Grad-3-Spätnebenwirkung. Ein weiterer Patient, der drei Monate nach Abschluß der Bestrahlung noch pneumonektomiert wurde, entwickelte als Folge der Operation zwei Grad-4-Komplikationen.

Schlußfolgerung

Sowohl das beobachtete Nebenwirkungsprofil als auch die präliminaren Therapieergebnisse weisen darauf hin, daß die Kombinationsbehandlung aus Bestrahlung und Interferon β beim lokoregionär fortgeschrittenen nichtkleinzelligen Bronchialkarzinom möglicherweise ein sinnvoller Ansatz ist, der im Rahmen einer Phase-III-Studie weiter untersucht werden sollte.

Abstract

Background

In-vitro and in-vivo studies demonstrated the radiosensitizing effect of interferon β on malignant tumor tissue as well as simultaneously a radioprotective effect on normal lung tissue. In this phase II study the outcome of combining radiotherapy with interferon β in patients with advanced non-small cell lung cancer was evaluated.

Patients and Method

From February 1994 until November 1996 14 patients with non-small cell lung cancer, stage IIIB were treated with locoregional radiation up to 59.4 Gy, with daily doses of 1.8 Gy and 5 fractions per week. Five million units of interferon β (Fiblaferon®) were given intravenously immediately preceding radiotherapy on the first 3 days of week 1, 3 and 5.

Results

Four of 14 patients (28.6%) showed complete response and 7 patients (50%) partial response, resulting in an overall response rate of 78.6%. After a mean follow-up time of 23.3 months the 1-, 2- and 3-year survival rates were 56.3%, 37.5% and 37.5%, respectively. The median survival time was 13 months. Three of 14 patients (21.4%) suffered from 7 Grade-3 acute side effects and 2 patients (14.3%) from 1 Grade-3 late toxicity in each case. One further patient, whose right lung was resected 3 months after completion of radiotherapy, developed as a consequence of this operation 2 Grade-4 complications.

Conclusion

Considering the toxicity and the preliminary results of combining irradiation and interferon β in the treatment of locally advanced non-small cell lung cancer it seems, that this procedure is worth to be tested in a phase III study.

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Authors and Affiliations

  1. Radiologische Klinik, Medizinischer Bereich Strahlentherapie, Zentralkrankenhaus Sankt-Jürgen-Straße, D-28205, Bremen

    Jörg Bund & Hans-Joachim Habermalz

  2. Pulmologische Klinik des Zentralkrankenhauses Bremen-Ost, Bremen, Deutschland

    Karin Eberhardt & Wilfried Hartmann

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  1. Jörg Bund
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Bund, J., Eberhardt, K., Hartmann, W. et al. Behandlung lokoregionär fortgeschrittener nichtkleinzelliger Bronchialkarzinome im Stadium IIIB mit Bestrahlung und Interferon β. Strahlenther Onkol 174, 300–305 (1998). https://doi.org/10.1007/BF03038543

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