Phase 1 Trial of Everolimus and Radiation Therapy for Salvage Treatment of Biochemical Recurrence in Prostate Cancer Patients Following Prostatectomy

Vivek Narayan, Neha Vapiwala, Rosemarie Mick, Pearl Subramanian, John P. Christodouleas, Justin E. Bekelman, Curtiland Deville, Ramji Rajendran, Naomi B. Haas

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Purpose In up to half of patients treated with salvage radiation therapy (SRT) for rising prostate-specific antigen levels, a second biochemical recurrence ultimately develops. Phosphatase and tensin homolog inactivation is implicated in prostate cancer progression, and upregulation of the mammalian target of rapamycin pathway can lead to tumor hypoxia and radioresistance. Everolimus is a mammalian target of rapamycin inhibitor with both antitumor and radiosensitizing effects. Methods and Materials We performed a phase 1 study using a modified 3 + 3 dose-escalation design to evaluate the safety and tolerability of everolimus in combination with standard SRT for the treatment of biochemical recurrence following prostatectomy. After a 2-week run-in period of everolimus daily therapy, patients received prostate bed irradiation with daily cone beam computed tomography localization in 37 fractions of 1.8 Gy each (total dose, 66.6 Gy). Patients were monitored for both acute (≤90 days) and chronic (>90 days) treatment-related toxicities. Results Eighteen patients received everolimus at dose levels of 5 mg (n=6), 7.5 mg (n=6), or 10 mg (n=6) daily in conjunction with SRT. No dose-limiting toxicities were observed. Common acute treatment-related toxicities included grade 1 or 2 mucositis (55.6%), grade 1 or 2 fatigue (38.9%), grade 1 or 2 rash (61.1%), and grade 1 urinary symptoms (61.1%). A grade 3 acute toxicity occurred in 4 patients (22.2%) (n=1 for rash, anemia, lymphopenia, and neutropenia), and no patients had a chronic toxicity of grade 3 or greater. After a median follow-up time of 17.8 months (range, 1.2-46.0 months), an undetectable prostate-specific antigen nadir was achieved in 9 patients (56.3%) and a second biochemical recurrence developed in 5 patients (31.3%). Conclusions Everolimus at a dose of ≤10 mg daily appears to be safe and tolerable in combination with fractionated post-prostatectomy radiation therapy.

Original languageEnglish (US)
Pages (from-to)355-361
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number2
StatePublished - Feb 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research


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