Neutropenia Prevention in the Treatment of Post-docetaxel Metastatic, Castration-resistant Prostate Cancer With Cabazitaxel and Prednisone: A Multicenter, Open-label, Single-arm Phase IV Study

Abstract

Introduction: Severe neutropenia is a dose-limiting factor that occurs in up to 82% of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel. This study evaluated the effectiveness of granulocyte colony-stimulating factor (G-CSF) plus ciprofloxacin as prophylaxis in post-docetaxel patients with mCRPC treated with cabazitaxel and at high risk for neutropenia.

Patients and methods: This was a phase IV, multicenter, open-label, single-arm interventional study with men aged ≥ 65 years (or < 65 years and ≥ 25% irradiated bone marrow), presenting with mCRPC after docetaxel failure, performance status ≤ 1, and life expectancy > 12 weeks. Cabazitaxel 25 mg/m² and prednisone were given on day 1, every 21 days. G-CSF was administered on days 2 to 8 of each cycle or until an absolute neutrophil count > 2000/mm³, and ciprofloxacin 1000 mg was given orally on days 5 to 12. The rate of neutropenia grade ≥ 3 during the first cycle (primary endpoint), and frequency of neutropenia grade ≥ 3, febrile neutropenia, diarrhea grade ≥ 3, prostate-specific antigen response, and quality of life during treatment (secondary end points) were estimated.

Results: We included 46 patients. The mean number of cabazitaxel cycles was 9.5. During the first cycle, 40.0% of patients had neutropenia grade ≥ 3, and 42.2% had at least 1 episode of neutropenia during treatment. Febrile neutropenia and diarrhea grade ≥ 3 occurred in 1 patient each. Twenty-nine (64.4%) patients achieved prostate-specific antigen response, and 77.2% improved quality of life scores in at least 1 visit.

Conclusions: Prophylactic G-CSF was effective in preventing neutropenia grade ≥ 3 and other hematologic complications during treatment with cabazitaxel 25 mg/m² in post-docetaxel patients with mCRPC at high risk for neutropenia. The role of prophyclatic ciprofloxacin to prevent febrile neutropenia in this setting is still unclear and needs to be further evaluated.

Keywords: Ciprofloxacin; Febrile neutropenia; Granulocyte colony-stimulating factor; Neutropenia; Second-line chemotherapy.