Second-line combination chemotherapy: A phase I study of ixabepilone, mitoxantrone, and prednisone in patients with metastatic hormone-refractory prostate cancer (HRPC) refractory to docetaxel-based therapy.

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Abstracts

2008 ASCO Annual Meeting

Second-line combination chemotherapy: A phase I study of ixabepilone, mitoxantrone, and prednisone in patients with metastatic hormone-refractory prostate cancer (HRPC) refractory to docetaxel-based therapy.

Sub-category:

Prostate Cancer

Category:

Genitourinary Cancer

Meeting:

2008 ASCO Annual Meeting

Session Type and Session Title:

General Poster Session, Genitourinary Cancer

Abstract No:

5151

Citation:

J Clin Oncol 26: 2008 (May 20 suppl; abstr 5151)

Author(s):

A. L. Harzstark, V. K. Weinberg, J. Sharib, D. C. Smith, M. H. Hussain, T. M. Beer, C. W. Ryan, P. Mathew, C. J. Ryan, E. J. Small, J. E. Rosenberg

Abstract:

Background: Mitoxantrone and prednisone (MP) and ixabepilone (Ix) both have modest activity as single agents for 2nd-line chemotherapy in docetaxel-refractory patients with HRPC and have demonstrated evidence of non-cross resistance, suggesting the potential for benefit with a combination of the two agents. Methods: Patients with metastatic HRPC and progression after 3 or more cycles of docetaxel were enrolled in a phase I multicenter study of the combination of Ix and MP administered on day 1 every 21 days along with prednisone 5 mg BID daily. Dose levels are listed below in a standard 3+3 phase I design. Toxicity was evaluated using CTC v3 criteria and responses were evaluated using PSA Consensus Criteria. Results: 32 pts have been treated on dose levels I through VIa to date. 20/32 pts (62.5%) had grade 3/4 neutropenia, 1 pt had grade 3 febrile neutropenia, and 1 pt had a grade 5 infection. Non-hematologic serious adverse events related to study drug included 1 episode of grade 3 diarrhea with dehydration and one episode of grade 3 emesis. DLTs are listed below. Due to prolonged neutropenia not identified until after dose-escalation, dose levels V and VI were repeated with pegfilgrastim on day 2 of each cycle (levels Va, VIa). Eight patients have experienced PSA responses, all at dose level 3 or higher; 6/17 (35%) of patients receiving full dose mitoxantrone (12 mg/m²) have had a PSA response. Conclusions: These results suggest that the combination is feasible and active and may require dosing with pegfilgrastim. Further exploration of activity will occur during the phase II expansion cohort once the MTD has been determined. This study was supported by the Cancer Therapy Evaluation Program of the NCI and the DOD Prostate Cancer Clinical Trials Consortium.

Dose Level	Mitoxantrone (mg/m²)	Ixabepilone (mg/m²)	Pegfilgrastim (mg)	DLTs	PSA Responses
I	8	20	-	0/3	0/3
II	8	25	-	0/3	0/3
III	10	25	-	0/3	1/3
IV	10	30	-	0/6	1/6
V	12	30	-	2/6: Grade 3 diarrhea, grade 4 neutropenia	2/6
VI	12	35	-	2/5: Grade 4 neutropenia (x2)	3/5
Va	12	30	6	0/3	1/3
VIa	12	35	6	1/3: Grade 5 infection	0/3

Abstract Disclosures

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy and are designated with a caret symbol (^) here and in the print version.

Associated Presentation(s):

1. Second-line combination chemotherapy: A phase I study of ixabepilone, mitoxantrone, and prednisone in patients with metastatic hormone-refractory prostate cancer (HRPC) refractory to docetaxel-based therapy.

Meeting: 2008 ASCO Annual Meeting
Presenter: Andrea L Harzstark, MD
Session: Genitourinary Cancer (General Poster Session)

Other Abstracts in this Sub-Category:

		1. Phase II trial of thalidomide (T), bevacizumab (Bv), and docetaxel (Doc) in patients (pts) with metastatic castration-refractory prostate cancer (mCRPC). Meeting: 2008 ASCO Annual Meeting Abstract No: 5000 First Author: Y. M. Ning Category: Genitourinary Cancer - Prostate Cancer
		2. Phase I study of docetaxel (Tax) and ¹⁵³Sm repetitively administered for castrate metastatic prostate cancer (CMPC). Meeting: 2008 ASCO Annual Meeting Abstract No: 5001 First Author: M. J. Morris Category: Genitourinary Cancer - Prostate Cancer
		3. A phase II randomized study of custirsen (OGX-011) combination therapy in patients with poor-risk hormone refractory prostate cancer (HRPC) who relapsed on or within six months of 1^st-line docetaxel therapy. Meeting: 2008 ASCO Annual Meeting Abstract No: 5002 First Author: F. Saad Category: Genitourinary Cancer - Prostate Cancer
		More...

Abstracts by A. L. Harzstark :

		1. A phase I/II study of dovitinib (TKI258), a FGFR and VEGFR inhibitor, in patients (pts) with advanced or metastatic renal cell cancer: Phase I results. Meeting: 2010 ASCO Annual Meeting Abstract No: 3057 First Author: E. Angevin Category: Developmental Therapeutics - Experimental Therapeutics - Tyrosine Kinase Inhibitors
		2. A phase II, single-arm study of AS1411 in metastatic renal cell carcinoma (RCC). Meeting: 2010 ASCO Annual Meeting Abstract No: 4590 First Author: J. E. Rosenberg Category: Genitourinary Cancer - Kidney Cancer
		3. Final results of a phase I study of CTLA-4 blockade in combination with GM-CSF for metastatic castration resistant prostate cancer (mCRPC). Meeting: 2010 ASCO Annual Meeting Abstract No: 4689 First Author: A. L. Harzstark Category: Genitourinary Cancer - Prostate Cancer
		More...

Presentations by A. L. Harzstark :

		1. Final results of a phase I study of CTLA-4 blockade in combination with GM-CSF for metastatic castration resistant prostate cancer (mCRPC). Meeting: 2010 ASCO Annual Meeting Presenter: Andrea Lynne Harzstark, MD Session: Genitourinary Cancer (General Poster Session)
		2. Genitourinary (Prostate) Cancer Meeting: 2010 ASCO Annual Meeting Co-Chair: Andrea Lynne Harzstark, MD Session: Genitourinary (Prostate) Cancer (Poster Discussion Session)
		3. Hypertension is associated with clinical outcome for patients (Pts) with metastatic renal cell carcinoma (RCC) treated with interferon and bevacizumab on CALGB 90206 Meeting: 2010 Genitourinary Cancers Symposium Presenter: Andrea Lynne Harzstark, MD Session: Reception and General Poster Session D: Testis, Bladder, Renal and Other GU Neoplasms (General Poster Session)
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Educational Book Manuscripts by A. L. Harzstark :

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