A phase I/II study of docetaxel in combination with pegylated liposomal doxorubicin in metastatic castration-resistant p
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ORIGINAL PAPER
A phase I/II study of docetaxel in combination with pegylated liposomal doxorubicin in metastatic castration‑resistant prostate cancer Damian A. Laber1,2,3 · Jennifer Eatrides1,3 · Michael V. Jaglal1,3 · Mintallah Haider1,3 · Nathan Visweshwar2 · Ankita Patel1,3 Received: 26 June 2020 / Accepted: 15 September 2020 / Published online: 26 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Taxanes and anthracyclines have been among the best-studied chemotherapy classes in castration-resistant prostate cancer (CRPC). Docetaxel (D) 75 mg/m2 every 3 weeks has been the standard first line chemotherapy for CRPC. Encapsulation of doxorubicin in polyethylene glycol-coated liposomes (PLD) was developed to enhance the safety and efficacy of conventional doxorubicin. We hypothesize that the combination of weekly low dose-D and PLD would result in a high response rate and low toxicity. Eligibility criteria included metastatic progressive CRPC, no prior D or PLD and good organ function. After a short phase I with no dose-limiting toxicity, D 30 mg/m2 was administered on days 1, 8 and 15; and PLD 30 mg/m2 on day 1 only, every 28 days. Thirty-seven patients were enrolled. The PSA response rate was 53%. Twenty-two subjects had measurable disease; one (5%) achieved complete response, five (23%) partial response, and twelve (54%) stable disease. Twentyseven patients (73%) manifested pain relief. The median time to progression was 3.7 months for all patients and 7.9 months for responders. Median overall survival was 16.3 months. Grade 4 neutropenia without infection and anemia occurred in 1 patient each. Grade 3 treatment-related toxicities included: 15% fatigue; 9% neutropenia, anemia and nausea; 6% dehydration and hand-foot syndrome; and 3% infection, febrile neutropenia, thrombosis, stomatitis, headache, vomiting, weight loss and weakness. In this non-comparative study D-PLD demonstrated a higher activity than previously reported with single agent D with favorable side effect profile. A phase 3 study would be needed to evaluate the true benefit of this combination. ClinicalTrials.gov Identifier: NCT00456989. Keywords Castration-resistant prostate cancer · Docetaxel · Doxorubicin · Phase 2 clinical trial · Polyethylene glycolcoated liposome
Introduction Many chemotherapeutic agents have demonstrated significant activity against castration-resistant prostate cancer (CRPC) [1, 2]. Docetaxel is an antineoplastic agent that * Damian A. Laber [email protected] 1
Section of Satellite Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
2
Division of Hematology/Oncology, Department of Medicine, Morsani School of Medicine, University of South Florida, Tampa, FL, USA
3
Department of Oncologic Sciences, Morsani School of Medicine, University of South Florida, Tampa, FL, USA
belongs to the taxoid family. The mechanism of action of D is estimated to be disruption of the microtubular network that is essential for mitotic and interphase ce
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