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Therapy

Oral 9-cis retinoic acid (Alitretinoin) in the treatment of myelodysplastic syndromes: results from a pilot study

Leukemia volume 14, pages 1583–1588 (2000)Cite this article

Abstract

A multicenter phase II study was initiated to investigate the efficacy, toxicity and tolerability of an oral regimen of 9-cis retinoic acid (9CRA) as a differentiation-inducing agent stimulating both retinoic acid receptor (RAR) and retinoic X receptor (RXR). Thirty patients with myelodysplastic syndromes (MDS) were enrolled into the study. The MDS subtypes were distributed as follows: 14 refractory anaemia (RA), four refractory anaemia with ringed sideroblasts (RARS), and 12 refractory anaemia with excess blasts (RAEB). The age ranged from 40 to 81 years (median 70). None of these had previously received treatment for MDS other than supportive therapy. 9CRA (Alitretinoin capsules, kindly provided by Allergan-Ligand Retinoid Therapeutics) was given daily at 60 mg/m2 p.o. for 1 week, followed by an intra-patient escalation to 100 mg/m2 during the second week, up to a maximum of 140 mg/m2. The planned treatment duration was 48 weeks. Twenty-five were available for assessment. One patient (4%) with RA achieved complete hematological remission. Four (16%), two with RA, two with RAEB, had minor responses resulting in decreased transfusion requirements or increased neutrophils. Thus, the overall response rate was 20% in evaluable patients with MDS and 17% in the study group on an intention-to-treat basis. The most frequent side-effects included headache (77%), dry skin (57%), arthralgias (30%), and rash (23%). In conclusion, although modest responses were noted in this study, the treatment tolerability was suboptimal. It is conceivable that a lower dosage schedule may be efficacious and better tolerated so enabling prolonged exposure which may be required to induce a differentiation effect. Leukemia (2000) 14, 1583–1588.

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Author notes

  1. WK Hofmann and WJ Kell: The first two authors contributed equally to the paper.

Authors and Affiliations

  1. Department of Hematology/Oncology, University of Frankfurt/Main, Germany

    WK Hofmann & D Hoelzer

  2. Department of Haematology, University of Wales College of Medicine, Cardiff, UK

    WJ Kell & AK Burnett

  3. Department of Hematology, Service des Maladies du Sang, Lille, France

    P Fenaux

  4. Department of Hematology, Hospital Mignot, Le Chesnay, France

    S Castaigne

  5. Department of Hematology/Oncology, Hannover Medical School, Germany

    A Ganser

  6. Department of Hematology, Hospital Saint Louis, Paris, France

    C Chomienne

  7. Allergan-Ligand Retinoid Therapeutics, High Wycombe, Bucks, UK

    R Burnett

  8. Ligand Pharmaceuticals, San Diego, CA, USA

    C Kowal

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Hofmann, W., Kell, W., Fenaux, P. et al. Oral 9-cis retinoic acid (Alitretinoin) in the treatment of myelodysplastic syndromes: results from a pilot study. Leukemia 14, 1583–1588 (2000). https://doi.org/10.1038/sj.leu.2401873

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