gms | German Medical Science

Introduction: Until recently, cytotoxic chemotherapy was considered to be a rather ineffective approach to the management of advanced prostate cancer, but newer agents have demonstrated potential for enhanced clinical activity. Especially docetaxel has shown promise for the treatment of hormone refractory prostate cancer (HRPCA) as monotherapy and in combination with other agents. The flare phenomenon is a known entity in androgen-deprivation therapy of advanced prostate cancer and it has also been described in palliative chemotherapy of HRPCA. Aim of this study was to evaluate the clinical impact of a PSA flare phenomenon in docetaxel treated HRPCA patients.

Methods: From 12/02 through 08/05 we traeted 47 HRPCA patients (mean age: 66 years; range 42-81). 21 patients received docetaxel monotherapy, 22 patients docetaxel + estramustin and 4 patients docetaxel + mitoxantrone. PSA-levels were determined prior to therapy and weekly thereafter. Patients were divided into 3 groups: Response (group 1), progression (group2) and flare (group 3). Flare was defined as initially rising PSA under therapy, dropping thereafter to values below baseline.The groups were compared for overall survival by Kaplan Meier analysis. All patients were evaluated for treatment associated toxicity according to CTC criteria.

Results: We observed a PSA flare phenomenon in 8 (18 %) of 44 evaluable patients, 24 (54,5 %) patients were primary responders and 12 (27,3 %) experienced progressive disease. In group 3 PSA rose to 107 – 180 % from baseline and then dropped to 21 – 68 %. Kaplan Meier Analysis showed significantly better overall median survival for groups 1 (18 months, p = 0,0005) and 3 (19 months, p = 0,006) as compared to group 2 (7 months). Survival in groups 1 and 3 was comparable. Grade 3 and 4 toxicity was below 5 % and equally distributed between the 3 groups.

Conclusion: In our limited patient cohort, PSA-flare phenomenon does not seem to be a clinically relevant issue in terms of overall survival. Thus, an initial rise of PSA under Docetaxel therapy in HRPCA does not indicate therapeutic failure and should not lead to early withdrawal from therapy in the absence of clinical signs of progression.