Feasibility of continuing docetaxel-based therapy in patients with metastatic castrate-resistant prostate cancer (mCRPC) that experience hypersensitivity reactions (HSR).

132 Background: Patients that receive docetaxel are observed closely for HSRs. Severe HSRs have been reported in patients premedicated with corticosteroids. The rate of allergic reactions reported in the TAX 327 trial (n=332) was 8% (any grade) and 1% (grade 3/4). In TAX 327 treatment was stopped after a total of 10 cycles of docetaxel. A recent trial conducted at the NCI has included patients treated with docetaxel-based therapy until radiographic progression with no cap on total dose or cycle number. Most patients have had significantly more than 10 cycles (median greater than 16 with a range of 1 to 48; however, some cycles did not include docetaxel). Given the increased incidence of HSR to docetaxel on our protocols, we developed guidelines for the clinical management of HSRs to docetaxel. Methods: We reviewed the literature on taxane HSRs and developed a 4-step clinical management guideline for the prevention and treatment of HSRs to docetaxel. Our guidelines utilize increasing amounts of H1/H2 antihistamines, corticosteroids, slower infusion rates of docetaxel, and/or decreasing concentrations of docetaxel. Results: From August 2009 to present, 63 mCRPC patients have been treated with docetaxel-based therapy. Twenty-three patients (37%) have experienced a HSR to docetaxel. HSRs initially occurred at cycle 1 (17%), cycle 2 (48%), cycle 3 (17%), cycle 4 (n=2), cycle 14 (n=1), cycle 16 (n=1). All patients were re-challenged with docetaxel using our 4-step clinical management guideline approach. Ten patients continued docetaxel without further HSRs. The remaining 13 patients continued to experience HSRs but were able to safely complete each infusion of docetaxel. No patients required discontinuation of therapy. Of the 23 patients with HSRs, 21 received more than 10 cycles of therapy with a median of 17 and a range of 1 to 38. Conclusions: Patients with mCRPC disease that is taxane sensitive and who experience HSR to docetaxel can continue to receive docetaxel safely. Most of these patients demonstrated a continued PSA, clinical, and radiographic response to therapy.