A Phase I study of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors potentially responsive to mitoxantrone

Lee P. Resta, Roberto Pili, Mario A. Eisenberger, Avery Spitz, Serina King, Jennifer Porter, Amy Franke, Ramesh Boinpally, Michael A. Carducci, Christopher J. Sweeney

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Purpose: To find the maximum tolerated dose (MTD) of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors. Methods: This was a Phase I study using cohort dose escalation of OSI-461 dosed orally twice daily in combination with mitoxantrone 12 mg/m2 given on Day 1 of each 21-day cycle. Results: OSI-461 dose was escalated to 1,000 mg po bid. One patient experienced a dose-limiting toxicity (DLT). Three patients discontinued the study due to adverse events (AE). Two patients (10%) had a partial response, and ten patients (50%) had stable disease as best response. Conclusion The combination of OSI-461 and mitoxantrone was well tolerated. Dose escalation was stopped because of toxicities in a concurrent Phase I trial. The response rate seen in patients with prostate cancer was comparable to response rates seen in trials of mitoxantrone and prednisone alone, and further studies of the combination of OSI-461 and mitoxantrone were not pursued.

Original languageEnglish (US)
Pages (from-to)431-438
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume67
Issue number2
DOIs
StatePublished - Feb 1 2011
Externally publishedYes

Keywords

  • Apoptosis
  • Clinical trial
  • Mitoxantrone
  • OSI-461

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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    Resta, L. P., Pili, R., Eisenberger, M. A., Spitz, A., King, S., Porter, J., Franke, A., Boinpally, R., Carducci, M. A., & Sweeney, C. J. (2011). A Phase I study of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors potentially responsive to mitoxantrone. Cancer Chemotherapy and Pharmacology, 67(2), 431-438. https://doi.org/10.1007/s00280-010-1328-7