1. A phase I/II study of docetaxel in combination with pegylated liposomal doxorubicin in metastatic castration-resistant prostate cancer.
- Author
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Laber DA, Eatrides J, Jaglal MV, Haider M, Visweshwar N, and Patel A
- Subjects
- Aged, Aged, 80 and over, Doxorubicin administration & dosage, Humans, Male, Middle Aged, Polyethylene Glycols administration & dosage, Treatment Outcome, Adenocarcinoma drug therapy, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Docetaxel administration & dosage, Doxorubicin analogs & derivatives, Prostatic Neoplasms, Castration-Resistant drug therapy
- Abstract
Taxanes and anthracyclines have been among the best-studied chemotherapy classes in castration-resistant prostate cancer (CRPC). Docetaxel (D) 75 mg/m
2 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. Twenty-seven 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.- Published
- 2020
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