Metronomic epirubicin plus ketoconazole after docetaxel in castration-resistant prostate cancer.

Abstract

e15146 Background: This single institution study compared epirubicin/ketoconazole/hydrocortisone (ME-K) as second-line chemotherapy after docetaxel in castration-resistant prostate cancer (CRPC). This combination was already in use prior to the advent of taxanes in CRPC (Sella A et al JCO 1994 Apr; 12 (4): 683-8) (Rangel C et al Urology 1992 Jun, 39 (6): 577-82). Methods: Men with CRPC treated at Sint-Maria Regional Hospital with ME-K as second-line chemotherapy after docetaxel, were retrospectively identified. Patients on ME-K received epirubicin 20 mg/m2on day 1, ketoconazole 3 x 200mg daily and hydrocortisone 20+10mg 3 weeks out of 4 (+ zoledronic acid if bone metastases). PSA response and time to PSA progression, as defined in Bubley, JCO 1999; 17: 3461-3467, were used to assess efficacy of chemotherapy. Clinical progression was defined as death or progression of symptoms requiring change of treatment regardless PSA levels. Results: 12 patients were treated with ME-K after docetaxel. Median age at start of second-line chemotherapy was 68y. Decline of PSA level of >50% was observed in 6 men (50%) receiving ME-K after docetaxel Partial response according to RECIST in 2 patients (lymph node, pleural). Besides alopecia, there were no significant side effects. Median time to clinical or PSA progression was 4 months in both groups (8 months in PSA responders and 2 months in non-responders in E-weekly-K group). Median overall survival was 14.5 months in patients treated with second-line E-weekly-K. Patient progression during first-line chemotherapy with docetaxel had a high chance of responding to n E-weekly-K as second-line chemotherapy and also had a subsequent longer TTP than under docetaxel. Conclusions: Metronomic, weekly low dose epirubicin and ketoconazole combination is an active second-line chemotherapy regimens in men with CRPC after docetaxel failure. This effect is most pronounced in patients progressing, whilst under docetaxel. Two patients with visceral metastases had a near complete response. The efficacy and toxicity of ME-K after docetaxel should be evaluated in larger prospective trials. No significant financial relationships to disclose.