A phase I study of everolimus and docetaxel in patients with castration-resistant prostate cancer.
Clin Genitourin Cancer
; 13(2): 113-23, 2015 Apr.
Article
em En
| MEDLINE
| ID: mdl-25450031
ABSTRACT
BACKGROUND:
The PTEN tumor suppressor is frequently lost in CRPC, with activation of Akt-mTOR signaling, driving growth. We conducted a phase I trial of the mTOR inhibitor, everolimus, and docetaxel in CRPC. PATIENTS ANDMETHODS:
Eligible patients had progressive, metastatic, chemotherapy-naive CRPC. Patients received everolimus 10 mg daily for 2 weeks and underwent a restaging FDG-PET/computed tomography scan. Patient cohorts were subsequently treated at 3 dose levels of everolimus with docetaxel 5 mg to 60 mg/m(2), 10 mg to 60 mg/m(2), and 10 mg to 70 mg/m(2). The primary end point was the safety and tolerability of combination therapy.RESULTS:
Accrual was 4 patients at level 1, 3 patients at level 2, and 8 patients at level 3. Common toxicities were hematologic and fatigue. Serum concentrations of everolimus when administered with docetaxel were 1.5 to 14.8 ng/mL in patients receiving 5 mg everolimus and 4.5 to 55.4 ng/mL in patients receiving 10 mg everolimus. Four patients had partial metabolic response (PMR) using FDG-PET, 12 had stable metabolic disease, and 2 had progressive metabolic disease after a 2-week treatment with everolimus alone. Five of 12 evaluable patients experienced a prostate-specific antigen (PSA) reduction ≥ 50% during treatment with everolimus together with docetaxel. All 4 patients with a PMR according to PET imaging experienced a PSA reduction in response to everolimus with docetaxel, and 3 of 4 had PSA declines ≥ 50%.CONCLUSION:
Everolimus 10 mg daily and docetaxel 60 mg/m(2) was safe in CRPC patients and these were the recommended doses in combination. FDG-PET response might serve as a biomarker for target inhibition by mTOR inhibitors.Palavras-chave
Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
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Fluordesoxiglucose F18
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Taxoides
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Neoplasias de Próstata Resistentes à Castração
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Everolimo
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Antineoplásicos
Limite:
Aged
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Genitourin Cancer
Ano de publicação:
2015
Tipo de documento:
Article