A, time course of PSA change in a patient with prostate cancer treated with 210 mg/m2 17-AAG on the continuous twice-weekly schedule (dose level 15). This patient had a 25% decline in PSA after beginning 17-AAG. Because of delayed grade 2 transaminitis, treatment was held on cycle 3, week 2 (day 53), and again during cycle 4, week 3 (day 81). Following the second treatment delay, 17-AAG was resumed but at the next lower dose level (150 mg/m2) on day 92. Following dose reduction, the patient’s PSA began to increase. B and C, serum levels of 17-AAG and 17-AG (B) and PBMC studies (C) from this patient. Pharmacodynamic studies of PBMCs show a heat shock response with induction of Hsp70 and down-regulation of Akt and Raf-1 by day 15.