A multicenter phase I study of cabazitaxel, mitoxantrone, and prednisone for chemotherapy-naïve patients with metastatic castration-resistant prostate cancer: A department of defense prostate cancer clinical trials consortium study.
Cabazitaxel 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.



To establish the maximally tolerated dose of the combination of cabazitaxel, mitoxantrone, and prednisone.



Patients with chemotherapy-naïve mCRPC were prospectively enrolled in a multicenter phase 1 trial. Cabazitaxel 20 and 25mg/m2were each evaluated in combination with escalating doses of mitoxantrone (starting dose 4mg/m2), given with prednisone 5mg twice daily.



A 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/m2plus 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).



The 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.
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.
Rahul
R
Aggarwal
Mayo Scottsdale Cancer Center, Scottsdale, AZ.
Alan
A
Bryce
Department of Medicine, Division of Hematology/Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.
Charles J
CJ
Ryan
Department of Medicine, Division of Hematology/Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.
Andrea
A
Harzstark
Department of Medicine, Vanderbilt University, Nashville, TN.
Christina
C
Derleth
Department of Medicine, Division of Hematology/Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.
Won
W
Kim
Department of Medicine, Division of Hematology/Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.
Terence
T
Friedlander
Department of Medicine, Division of Hematology/Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.
Amy M
AM
Lin
Department of Medicine, Division of Hematology/Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.
Tammy
T
Rodvelt-Bagchi
Department of Medicine, Division of Hematology/Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.
Mallika
M
Dhawan
Department of Medicine, Division of Hematology/Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.
Li
L
Zhang
Department of Medicine, Division of Hematology/Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.
Mina
M
Lee
Mayo Scottsdale Cancer Center, Scottsdale, AZ.
Eric
E
Siebeneck
Department of Medicine, Division of Hematology/Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.
Jeffrey
J
Hough
Department of Medicine, Division of Hematology/Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.
Eric J
EJ
Small
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D011241:Prednisone / Q000008:administration & dosage; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
D043823:Taxoids; C552428:cabazitaxel; D008942:Mitoxantrone; D011241:Prednisone
Cabazitaxel; Castration-resistant; Chemotherapy; Clinical trial; Metastatic; Mitoxantrone; Phase 1; Prednisone; Prostate cancer