A transient rise in serum alkaline phosphatase (ALP) activity (ALP flare) after androgen deprivation in prostate cancer patients with bone metastases has been previously correlated with both response to therapy and poor prognosis. In the present study we analyzed data coming from an Italian multicenter phase III, trial aimed to compare the efficacy of treatment with goserelin alone with that of goserelin plus mitomycin C. Sixty-seven bone metastatic patients were enrolled: 32 were treated with goserelin and 35 with and goserelin plus mitomycin. 58 cases had ALP measured every month; and were considered for flare assessment. Remarkably elevated ALP and PSA levels at baseline were significantly correlated with poor prognosis. The addition of mitomycin to goserelin resulted in a greater percent reduction of PSA values with respect to goserelin alone but did not augment the time to progression and overall survival. The monthly profile of ALP serum levels was superimposable in patients assigned to hormone therapy or chemotherapy plus hormone therapy. Patients showing a flare in ALP activity (transient rise > 15% in ALP values with respect to baseline at the first month) were classified as responders to therapy or as having stable disease upon PSA evaluation and/or at bone pain assessment, but had a shorter time to progression (median 12 months) in comparison to those showing a different ALP pattern (median 23 months). The measurement of flare in ALP activity during androgen suppression with or without concomitant mitomycin administration, may permit the early identification of patients who are likely to progress rapidly, and hence be candidate for more aggressive treatments.