• Rahul Aggarwal, Alan Bryce, Charles J Ryan, Andrea Harzstark, Christina Derleth, Won Kim, Terence Friedlander, Amy M Lin, Tammy Rodvelt-Bagchi, Mallika Dhawan, Li Zhang, Mina Lee, Eric Siebeneck, Jeffrey Hough, and Eric J Small.
• Department of Medicine, Division of Hematology/Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA. Electronic address: Rahul.Aggarwal@ucsf.edu.
• Urol. Oncol. 2017 Apr 1; 35 (4): 149.e7-149.e13.

BackgroundCabazitaxel plus prednisone has significant activity in patients with chemotherapy-naïve and pretreated metastatic castration-resistant prostate cancer (mCRPC). Mitoxantrone has antitumor activity in mCRPC and nonoverlapping mechanism of action and toxicity profile.ObjectiveTo establish the maximally tolerated dose of the combination of cabazitaxel, mitoxantrone, and prednisone.Methods And MaterialsPatients with chemotherapy-naïve mCRPC were prospectively enrolled in a multicenter phase 1 trial. Cabazitaxel 20 and 25mg/m2 were each evaluated in combination with escalating doses of mitoxantrone (starting dose 4mg/m2), given with prednisone 5mg twice daily.ResultsA total of 25 patients were enrolled, with median age of 67 (range: 51-78) and prostate-specific antigen of 66.8ng/ml (range: 3-791.2). There were 4 dose-limiting toxicities (febrile neutropenia, n = 3; sepsis, n = 1). The maximally tolerated dose was cabazitaxel 20mg/m2 plus mitoxantrone 12mg/m2. The most common treatment-related grade≥3 related adverse events included neutropenia (n = 8; 32%), febrile neutropenia (n = 5; 20%), and thrombocytopenia (n = 4; 16%). The median number of treatment cycles was 8 (range: 2 to 19+). Decline in prostate-specific antigen to≥50% from baseline was observed in 15 patients (60%). Objective responses were observed in 10/14 (71%) evaluable patients. The median radiographic progression-free survival was 14.5 months (95% CI: 8.0-not reached (NR)), and median overall survival was 23.3 months (95% CI: 14.3-NR).ConclusionsThe approved single-agent doses of mitoxantrone and cabazitaxel were safely combined. The combination led to durable tumor responses in most patients. Further study of the combination is warranted.Copyright © 2017 Elsevier Inc. All rights reserved.

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