Vorinostat in refractory soft tissue sarcomas – Results of a multi-centre phase II trial of the German Soft Tissue Sarcoma and Bone Tumour Working Group (AIO)

Publication date: September 2016
Source:European Journal of Cancer, Volume 64
Author(s): Thomas Schmitt, Regine Mayer-Steinacker, Frank Mayer, Viktor Grünwald, Jochen Schütte, Jörg T. Hartmann, Bernd Kasper, Johannes Hüsing, Jacek Hajda, Gregor Ottawa, Gunhild Mechtersheimer, Gerd Mikus, Jürgen Burhenne, Lorenz Lehmann, Christoph E. Heilig, Anthony D. Ho, Gerlinde Egerer
IntroductionNew treatment options for patients with metastatic Soft Tissue Sarcoma are urgently needed. Preclinical studies suggested activity of vorinostat, a histone deacetylase inhibitor.MethodsA multi-centre, open-label, non-randomised phase II trial to investigate the efficacy and safety of vorinostat in patients with locally advanced or metastatic Soft Tissue Sarcoma failing 1st-line anthracycline-based chemotherapy was initiated. Patients were treated with vorinostat 400 mg po qd for 28 d followed by a treatment-free period of 7 d, representing a treatment cycle of 5 weeks. Restaging was performed every three cycles or at clinical progression.ResultsBetween 06/10 and 09/13, 40 Soft Tissue Sarcoma patients were treated with vorinostat at seven participating centres. Patients had received 1 (n=8, 20%), 2 (n=10, 25%) or ≥3 (n=22, 55%) previous lines of chemotherapy. Best response after three cycles of treatment was stable disease (n=9, 23%). Median progression-free survival and overall survival were 3.2 and 12.3 months, respectively. Six patients showed long-lasting disease stabilisation for up to ten cycles. Statistical analyses failed to identify baseline predictive markers in this subgroup. Major toxicities (grade ≥III) included haematological toxicity (n=6, 15%) gastrointestinal disorders (n=5, 13%), fatigue (n=4, 10%), musculoskeletal pain (n=4, 10%), and pneumonia (n=2, 5%).ConclusionIn a heavily pre-treated patient population, objective response to vorinostat was low. However, a small subgroup of patients had long-lasting disease stabilisation. Further studies aiming to identify predictive markers for treatment response as well as exploration of combination regimens are warranted.Trial registration: NCT00918489 (ClinicalTrials.gov)EudraCT-number: 2008-008513-19



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