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

doi:10.1007/s00280-010-1328-7

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

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 language	English (US)
Pages (from-to)	431-438
Number of pages	8
Journal	Cancer Chemotherapy and Pharmacology
Volume	67
Issue number	2
DOIs	https://doi.org/10.1007/s00280-010-1328-7
State	Published - Feb 2011

Keywords

Apoptosis
Clinical trial
Mitoxantrone
OSI-461

ASJC Scopus subject areas

Oncology
Toxicology
Pharmacology
Cancer Research
Pharmacology (medical)

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10.1007/s00280-010-1328-7

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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

Resta, LP, Pili, R, Eisenberger, MA, Spitz, A, King, S, Porter, J, Franke, A, Boinpally, R, Carducci, MA & Sweeney, CJ 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, vol. 67, no. 2, pp. 431-438. https://doi.org/10.1007/s00280-010-1328-7

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

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.",

keywords = "Apoptosis, Clinical trial, Mitoxantrone, OSI-461",

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

note = "Funding Information: Acknowledgment This work was financially supported by OSI Pharmaceuticals Inc.",

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doi = "10.1007/s00280-010-1328-7",

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AU - Resta, Lee P.

AU - Pili, Roberto

AU - Eisenberger, Mario A.

AU - Spitz, Avery

AU - King, Serina

AU - Porter, Jennifer

AU - Franke, Amy

AU - Boinpally, Ramesh

AU - Carducci, Michael A.

AU - Sweeney, Christopher J.

N1 - Funding Information: Acknowledgment This work was financially supported by OSI Pharmaceuticals Inc.

PY - 2011/2

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N2 - 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.

AB - 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.

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

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