Hepatic intra-arterial versus intravenous fotemustine in patients with liver metastases from uveal melanoma (EORTC 18021): a multicentric randomized trial |
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| Affiliation: | 1. Oncology Department, University Hospital, Lausanne, Switzerland;2. Institut Curie, Paris, France;3. EORTC Headquarters, Brussels;4. Centre du Cancer, Cliniques Universitaires Saint-Luc, Brussels, Belgium;5. Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland;6. European Institute of Oncology, Milan, Italy;7. Clatterbridge Centre for Oncology, Wirral, UK;8. West German Cancer Center, University of Essen Medical School, Essen, Germany;9. University Hospital Bordeaux Saint André, Bordeaux;10. Léon-Bérard Cancer Centre, Lyon, France;11. Antwerp University Hospital, Edegem, Belgium;12. Universitätsklinik Erlangen, Erlangen, Germany;13. Centre Jean Perrin, Clermont-Ferrand, France;14. University Hospital Essen, Essen;15. Department of Hematology and Medical Oncology, Charité, CBF, Berlin, Germany |
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| Abstract: | BackgroundIn uveal melanoma (UM) with metastatic disease limited to the liver, the effect of an intrahepatic treatment on survival is unknown. We investigated prospectively the efficacy and toxicity of hepatic intra-arterial (HIA) versus systemic (IV) fotemustine in patients with liver metastases from UM.Patients and methodsPatients were randomly assigned to receive either IV or HIA fotemustine at 100 mg/m2 on days 1, 8, 15 (and 22 in HIA arm only) as induction, and after a 5-week rest period every 3 weeks as maintenance. Primary end point was overall survival (OS). Response rate (RR), progression-free survival (PFS) and safety were secondary end points.ResultsAccrual was stopped after randomization of 171 patients based on the results of a futility OS analysis. A total of 155 patients died and 16 were still alive [median follow-up 1.6 years (range 0.25–6 years)]. HIA did not improve OS (median 14.6 months) when compared with the IV arm (median 13.8 months), hazard ratio (HR) 1.09; 95% confidence interval (CI) 0.79–1.50, log-rank P = 0.59. However, there was a significant benefit on PFS for HIA compared with IV with a median of 4.5 versus 3.5 months, respectively (HR 0.62; 95% CI 0.45–0.84, log-rank P = 0.002). The 1-year PFS rate was 24% in the HIA arm versus 8% in the IV arm. An improved RR was seen in the HIA (10.5%) compared with IV treatment (2.4%). In the IV arm, the most frequent grade ≥3 toxicity was thrombocytopenia (42.1%) and neutropenia (62.6%), compared with 21.2% and 28.7% in the HIA arm. The main grade ≥3 toxicity related to HIA was catheter complications (12%) and liver toxicity (4.5%) apart from two toxic deaths.ConclusionHIA treatment with fotemustine did not translate into an improved OS compared with IV treatment, despite better RR and PFS. Intrahepatic treatment should still be considered as experimental.EudraCT number and ClinicalTrials.gov identifier2004-002245-12 and NCT00110123. |
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