Role of sorafenib in overcoming resistance of chemotherapy-failure castration-resistant prostate cancer

Andrew Meyer, Peter Cygan, Kathy Tolzien, Angel G. Galvez, Jacob D. Bitran, Timothy M. Lestingi, Chadi Nabhan

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Background Sorafenib promotes apoptosis through downstream pathways that can be deregulated in CRPC. We hypothesized that sorafenib could overcome chemotherapy resistance in CRPC. Patients and Methods Eligible patients were those whose disease had progressed during chemotherapy (docetaxel or mitoxantrone) or within 12 weeks of stopping either. Patients then continued or resumed their last chemotherapy regimen with the addition of sorafenib 400 mg twice daily. Patients received a maximum of 6 cycles of chemotherapy/sorafenib followed by sorafenib alone until disease progression. The primary end point was combination safety. Secondary end points were overall response, percentage of SD, and time to progression (TTP). Results Twenty-two patients (21 evaluable) were enrolled (16 patients with Gleason score ≥ 7). Median age was 68 years (range, 59-83 years). Median prostate-specific antigen (PSA) was 142 ng/dL (range, 13.6-9584). Visceral and bone disease were present combined in 9 patients (41%). Ten patients (47.6%) showed biochemical response (19% with > 50% PSA decline) and 16 patients (76%) achieved radiographic stability (according to Response Evaluation Criteria for Solid Tumors) after starting sorafenib for a median duration of 6 months (range, 4-12 months). Grade 3/4 nonhematologic toxicities were fatigue (n = 7, 32%), palmar-plantar erythrodysesthesia (n = 4, 18%). Dose reduction of sorafenib occurred at least once in 15 patients (68%) because of palmar-plantar erythrodysesthesia (22%) and fatigue (22%). With a median follow-up of 19 months (range, 3-46 months), median overall survival was 8 months. TTP according to PSA level was 3 months and TTP according to imaging studies and/or clinically was 6 months. Median number of treatment cycles given was 6 (range, 1-10). Conclusion Sorafenib can be combined safely with chemotherapy and in some patients overcomes chemotherapy resistance.

Original languageEnglish (US)
Pages (from-to)100-105
Number of pages6
JournalClinical Genitourinary Cancer
Volume12
Issue number2
DOIs
StatePublished - Apr 2014

All Science Journal Classification (ASJC) codes

  • Oncology
  • Urology

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