A phase I/II study of sepantronium bromide (YM155, survivin suppressor) with paclitaxel and carboplatin in patients with advanced non-Small-Cell lung cancer

R. J. Kelly, A. Thomas, A. Rajan, G. Chun, A. Lopez-Chavez, E. Szabo, S. Spencer, C. A. Carter, U. Guha, S. Khozin, S. Poondru, C. Van Sant, A. Keating, S. M. Steinberg, W. Figg, G. Giaccone

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

Background: This phase I/II study examined the safety and efficacy of Sepantronium Bromide (S), a small-molecule selective survivin suppressant, administered in combination with carboplatin (C) andpaclitaxel (P). Patients and methods: Forty-one patients were treated on study. Twenty-two patients received escalating doses of S (3.6-12 mg/m2) and 19 with untreated stage IV non-small-cell lung cancer (NSCLC) were treated with the maximum tolerated dose of 10 mg/m2 in combination with standard dosesof C (AUC6) and P (200 mg/m2) for six cycles. S was administered as a continuous intravenous infusion(CIVI) over 72 h in 21-day treatment cycles. Study end points included safety and toxic effect, response rate, progression-free and overall survival (PFS and OS), as well as exploratory pharmacodynamic correlates. Results: Treatment with S was well tolerated, and toxic effects were mostly hematologicalin the phase II study. Two (11%) partial responses were observed with a median PFS of 5.7 months and median OS 16.1 months. Pharmacodynamic analysis did not demonstrate an association with response. Conclusion: The combination of S (10 mg/m2/day 72-h CIVI) administered with C and P every 3 weeks exhibited a favorable safety profile but failed to demonstrate an improvement in response rate in advanced NSCLC. Clinical trial number: NCT01100931.

Original languageEnglish (US)
Pages (from-to)2601-2606
Number of pages6
JournalAnnals of Oncology
Volume24
Issue number10
DOIs
StatePublished - Oct 1 2013

    Fingerprint

Keywords

  • Apoptosis
  • Non-Small-Cell lung cancer
  • Sepantronium bromide
  • Survivin

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Kelly, R. J., Thomas, A., Rajan, A., Chun, G., Lopez-Chavez, A., Szabo, E., Spencer, S., Carter, C. A., Guha, U., Khozin, S., Poondru, S., Van Sant, C., Keating, A., Steinberg, S. M., Figg, W., & Giaccone, G. (2013). A phase I/II study of sepantronium bromide (YM155, survivin suppressor) with paclitaxel and carboplatin in patients with advanced non-Small-Cell lung cancer. Annals of Oncology, 24(10), 2601-2606. https://doi.org/10.1093/annonc/mdt249