A phase i study of everolimus and docetaxel in patients with castration-resistant prostate cancer

Kevin D. Courtney, Judith B. Manola, Aymen A. Elfiky, Robert Ross, William K. Oh, Jeffrey T. Yap, Annick D. Van Den Abbeele, Christopher W. Ryan, Tomasz M. Beer, Massimo Loda, Carmen Priolo, Philip Kantoff, Mary Ellen Taplin

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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 and Methods 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/m2, 10 mg to 60 mg/m2, and 10 mg to 70 mg/m2. 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/m2 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.

Original languageEnglish (US)
Pages (from-to)113-123
Number of pages11
JournalClinical Genitourinary Cancer
Issue number2
StatePublished - Apr 1 2015


  • PI3K
  • PTEN
  • Positron emission tomography
  • Prostatic adenocarcinoma
  • mTOR

ASJC Scopus subject areas

  • Oncology
  • Urology


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