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Aktuelle Urol 2006; 37(6): 429-435
DOI: 10.1055/s-2006-932207
Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Thalidomid/Interleukin-2 in der Second-line-Therapie des metastasierten Nierenzellkarzinoms - Ergebnisse einer Pilotstudie

Second-Line Thalidomide/IL-2 Therapy in Metastatic Kidney Cancer - Results of a Pilot StudyA.  J.  Schrader1 , A.  Heidenreich2 , A.  Hegele1 , P.  Olbert1 , Z.  Varga1 , R.  Hofmann1
  • 1Klinik für Urologie und Kinderurologie Marburg, Universitätsklinikum Gießen und Marburg
  • 2Klinik für Urologie, Universitätsklinikum Köln
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Publication History

Publication Date:
13 November 2006 (online)

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Zusammenfassung

Fragestellung: Vor dem Hintergrund viel versprechender Ergebnisse aus der First-line-Therapie des metastasierten Nierenzellkarzinoms untersuchten wir Effektivität und Nebenwirkungsprofil kombinierter IL-2/Thalidomid-Therapie bei Patienten mit immun(chemo)therapierefraktärem Nierenzellkarzinom. Material und Methode: 14 Patienten mit therapierefraktärem Nierenzellkarzinom und weiter bestehendem Therapiewunsch wurden mit Thalidomid (p. o., 200 mg/d, Tag 1 + 2, Woche 0; anschließend 400 mg/d) in Kombination mit IL-2 (s. c., 7 MIU/m2, Tag 1 - 5, Woche 1 - 4) behandelt. Die Zykluslänge betrug 6 Wochen. Das Therapieansprechen wurde nach je 2 Zyklen reevaluiert. Ergebnisse: Objektive Tumorremissionen konnten nicht erreicht werden, 4 Patienten (29 %) zeigten eine Stabilisierung ihrer Erkrankung für 21, 15, 13 und 9 Monate. Das Nebenwirkungsspektrum bestand überwiegend aus erst- bis drittgradiger Fatigue und Obstipation sowie grippeähnlichen Beschwerden. Ein Patient brach bereits nach 3 Wochen die Behandlung wegen eines therapierefraktären paralytischen Ileus ab. Eine zweite Patientin beendete die Behandlung nach 7 Wochen aufgrund zunehmender Verwirrtheit. 11 Patienten benötigten eine IL-2-Dosisreduktion im Verlauf der Therapie, die im Median über 19 Wochen (3 - 44 Wochen) durchgeführt wurde. Das mittlere Gesamtüberleben betrug 22 Monate. Schlussfolgerungen: Die ambulante IL-2/Thalidomid-Therapie zur Behandlung des Patienten mit zytokinrefraktärem Nierenzellkarzinom und weiterhin bestehendem Therapiewunsch ist prinzipiell möglich. Toxizität und Kosten sind jedoch beträchtlich, das Ansprechen limitiert. Die Frage nach einer effizienten Second-line-Therapie bleibt unbeantwortet; die hier untersuchte Kombinationstherapie scheint keine rationelle Option für die Behandlung des vortherapierten progredienten Nierenzellkarzinoms darzustellen.

Abstract

Purpose: On the basis of promising first-line data we have evaluated the safety and efficacy of a combination therapy comprising interleukin-2 (IL-2) and thalidomide in patients with metastatic renal cell carcinoma (RCC) refractory to both immuno- and chemotherapy. Patients and Methods: 14 patients with progressive metastatic RCC, in whom prior immunochemotherapy had failed but who desired further active therapy, were enrolled in this study. Oral thalidomide was started at 200 mg/d and escalated after two days to 400 mg/d at week 0. IL-2 at 7 MIU/m2 was given by subcutaneous injection, starting at week 1, days 1 to 5, weeks 1 to 4, with no IL-2 at weeks 5 and 6. The response was assessed every other therapy cycle. Results: 12 patients were evaluable for response. There was no objective response; 4 patients showed stable disease for 21, 15, 13 and 9 months, respectively. Toxicities were predominantly grade 1 - 3 and included somnolence and constipation, as well as flu-like symptoms associated with IL-2. However, one patient developed serious constipation which led to a paralytic ileus and discontinuation of treatment. Another patient left the study after seven weeks due to increasing confusion. 11 patients required IL-2 dose reduction. Time on therapy ranged from 3 - 44 weeks (median, 19 weeks). Median overall survival was 22 months. Up to date, all patients have discontinued treatment. Conclusions: We conclude that outpatient administration of thalidomide/IL-2 is feasible in patients with heavily pretreated and progressive RCC who desire further active treatment. However, toxicity and costs are considerable and the clinical benefit is uncertain. Therefore thalidomide/IL-2 may not represent a promising therapeutic approach for this subgroup of patients.

Schlüsselwörter

Nierenzellkarzinom - IL-2 - IFN - Thalidomid - Second-line-Therapie - Progression - Überleben

Key words

IL-2 - IFN - thalidomide - second-line therapy - renal cell carcinoma - progression - remission - survival - review

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Dr. med. Andres Jan Schrader

Klinik für Urologie, Universitätsklinik Marburg

Baldingerstraße

35043 Marburg

Phone: +49-6421-286-2479

Fax: +49-6421-286-5590

Email: ajschrader@gmx.de

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