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)

Eur J Cancer. 2016 Sep;64:74-82. doi: 10.1016/j.ejca.2016.05.018. Epub 2016 Jun 28.


Introduction: New treatment options for patients with metastatic Soft Tissue Sarcoma are urgently needed. Preclinical studies suggested activity of vorinostat, a histone deacetylase inhibitor.

Methods: A 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.

Results: Between 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%).

Conclusion: In 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.

Keywords: Histone deacetylase-inhibition; Locally advanced; Metastatic; Soft Tissue Sarcoma; Vorinostat.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Female
  • Germany
  • Humans
  • Hydroxamic Acids / adverse effects
  • Hydroxamic Acids / therapeutic use*
  • Male
  • Middle Aged
  • Sarcoma / drug therapy*
  • Sarcoma / pathology
  • Sarcoma / secondary
  • Soft Tissue Neoplasms / drug therapy*
  • Soft Tissue Neoplasms / pathology
  • Survival Analysis
  • Treatment Outcome
  • Vorinostat
  • Young Adult


  • Antineoplastic Agents
  • Hydroxamic Acids
  • Vorinostat

Associated data

  • ClinicalTrials.gov/NCT00918489