Assessment of molecularly targeted cytostatic or antiangiogenic agents

Bellmunt [53] and others expressed concern that PSA response criteria are not established to properly evaluate molecularly targeted cytostatic or anti-angiogenic agents [54]; therefore, certain drug-specific limitations may exist when using PSA or PSA-DT as an indicator of progression or response. One clear example was noted in a study of sorafenib (Nexavar) in castrate resistant prostate cancer, in which two patients with PSA progression were found to have dramatic resolution of bony disease [55]. Therapy-associated PSA "surge" has been described after effective chemotherapy. PSA surge occurs with Samarium153 radiotherapy, androgen deprivation and chemotherapy and is generally transient. The surge may be due to rapid lysis of prostate cancer cells thus spilling intracellular contents into the intravascular space [56]. Similarly, 10 of 16 patients who discontinued sorafenib and did not receive other therapy demonstrated post-discontinuation PSA declines of 7-52% [57]. The review by Bell-munt [58, 59] notes that several targeted therapies caused prolongation of the PSA-DT as well as significant suppression of PSA levels. The era of targeted therapy for prostate cancer is just beginning and will require changes in how we interpret PSA kinetics.

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