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

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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 2013
Externally publishedYes

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Carboplatin
Paclitaxel
Non-Small Cell Lung Carcinoma
Poisons
Safety
Intravenous Infusions
Maximum Tolerated Dose
Disease-Free Survival
Clinical Trials
Therapeutics
YM 155

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

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

In: Annals of Oncology, Vol. 24, No. 10, 10.2013, p. 2601-2606.

Research output: Contribution to journalArticle

Kelly, RJ, Thomas, A, Rajan, A, Chun, G, Lopez-Chavez, A, Szabo, E, Spencer, S, Carter, CA, Guha, U, Khozin, S, Poondru, S, Van Sant, C, Keating, A, Steinberg, SM, 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, vol. 24, no. 10, pp. 2601-2606. https://doi.org/10.1093/annonc/mdt249
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. / A phase I/II study of sepantronium bromide (YM155, survivin suppressor) with paclitaxel and carboplatin in patients with advanced non-Small-Cell lung cancer. In: Annals of Oncology. 2013 ; Vol. 24, No. 10. pp. 2601-2606.
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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.",
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T1 - A phase I/II study of sepantronium bromide (YM155, survivin suppressor) with paclitaxel and carboplatin in patients with advanced non-Small-Cell lung cancer

AU - Kelly, R. J.

AU - Thomas, A.

AU - Rajan, A.

AU - Chun, G.

AU - Lopez-Chavez, A.

AU - Szabo, E.

AU - Spencer, S.

AU - Carter, C. A.

AU - Guha, U.

AU - Khozin, S.

AU - Poondru, S.

AU - Van Sant, C.

AU - Keating, A.

AU - Steinberg, S. M.

AU - Figg, W.

AU - Giaccone, G.

PY - 2013/10

Y1 - 2013/10

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Non-Small-Cell lung cancer

KW - Sepantronium bromide

KW - Survivin

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