A Phase I/II Study of Sepantronium Bromide (YM155, Survivin Suppressor) With Paclitaxel and Carboplatin in Patients With Advanced Non-Small-Cell Lung Cancer

Ann Oncol. 2013 Oct;24(10):2601-6. doi: 10.1093/annonc/mdt249. Epub 2013 Jul 14.

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) and paclitaxel (P).

Patients and methods: Forty-one patients were treated on study. Twenty-two patients received escalating doses of S (3.6-12 mg/m(2)) and 19 with untreated stage IV non-small-cell lung cancer (NSCLC) were treated with the maximum tolerated dose of 10 mg/m(2) in combination with standard doses of C (AUC6) and P (200 mg/m(2)) 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 hematological in 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/m(2)/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.

Keywords: apoptosis; non-small-cell lung cancer; sepantronium bromide; survivin.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Apoptosis / drug effects
  • Carboplatin / adverse effects
  • Carboplatin / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Disease-Free Survival
  • Female
  • Humans
  • Imidazoles / adverse effects
  • Imidazoles / blood
  • Imidazoles / therapeutic use*
  • Inhibitor of Apoptosis Proteins / antagonists & inhibitors*
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Naphthoquinones / adverse effects
  • Naphthoquinones / blood
  • Naphthoquinones / therapeutic use*
  • Paclitaxel / adverse effects
  • Paclitaxel / therapeutic use
  • Survival
  • Survivin
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Phytogenic
  • BIRC5 protein, human
  • Imidazoles
  • Inhibitor of Apoptosis Proteins
  • Naphthoquinones
  • Survivin
  • YM 155
  • Carboplatin
  • Paclitaxel

Associated data

  • ClinicalTrials.gov/NCT01100931