TY - JOUR
T1 - A Phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with hormone-refractory metastatic prostate cancer
AU - Heath, Elisabeth I.
AU - Hillman, David W.
AU - Vaishampayan, Ulka
AU - Sheng, Shijie
AU - Sarkar, Fazlul
AU - Harper, Felicity
AU - Gaskins, Melvin
AU - Pitot, Henry C.
AU - Tan, Winston
AU - Ivy, S. Percy
AU - Pili, Roberto
AU - Carducci, Michael A.
AU - Erlichman, Charles
AU - Liu, Glenn
PY - 2008/12/1
Y1 - 2008/12/1
N2 - Purpose:17-Allylamino-17-demethoxygeldanamycin (17-AAG) is a benzoquinone ansamycin antibiotic with antiproliferative activity in several mouse xenograft models, including prostate cancer models. A two-stage phase II study was conducted to assess the activity and toxicity profile of 17-AAG administered to patients with metastatic, hormone-refractory prostate cancer. Experimental Design:Patients with at least one prior systemic therapy and a rising prostate-specific antigen (PSA) were eligible. Patients received 17-AAG at a dose of 300 mg/m 2 i.v. weekly for 3 of 4 weeks. The primary objective was to assess the PSA response. Secondary objectives were to determine overall survival, to assess toxicity, and to measure interleukin-6, interleukin-8, and maspin levels and quality of life. Results:Fifteen eligible patients were enrolled. The median age was 68 years and the median PSA was 261ng/mL. Patients received 17-AAG for a median number of two cycles. Severe adverse events included grade 3 fatigue (four patients), grade 3 lymphopenia (two patients), and grade 3 back pain (two patients). The median PSA progression-free survival was 1.8 months (95% confidence interval, 1.3-3.4 months).The 6-month overall survival was 71% (95% confidence interval, 52-100%). Conclusions:17-AAG did not show any activity with regard to PSA response. Due to insufficient PSA response, enrollment was stopped at the end of first stage per study design. The most significant severe toxicity was grade 3 fatigue. Further evaluation of 17-AAG at a dose of 300 mg/ m 2 i.v. weekly as a single agent in patients with metastatic, hormone-refractory prostate cancer who received at least one prior systemic therapy is not warranted.
AB - Purpose:17-Allylamino-17-demethoxygeldanamycin (17-AAG) is a benzoquinone ansamycin antibiotic with antiproliferative activity in several mouse xenograft models, including prostate cancer models. A two-stage phase II study was conducted to assess the activity and toxicity profile of 17-AAG administered to patients with metastatic, hormone-refractory prostate cancer. Experimental Design:Patients with at least one prior systemic therapy and a rising prostate-specific antigen (PSA) were eligible. Patients received 17-AAG at a dose of 300 mg/m 2 i.v. weekly for 3 of 4 weeks. The primary objective was to assess the PSA response. Secondary objectives were to determine overall survival, to assess toxicity, and to measure interleukin-6, interleukin-8, and maspin levels and quality of life. Results:Fifteen eligible patients were enrolled. The median age was 68 years and the median PSA was 261ng/mL. Patients received 17-AAG for a median number of two cycles. Severe adverse events included grade 3 fatigue (four patients), grade 3 lymphopenia (two patients), and grade 3 back pain (two patients). The median PSA progression-free survival was 1.8 months (95% confidence interval, 1.3-3.4 months).The 6-month overall survival was 71% (95% confidence interval, 52-100%). Conclusions:17-AAG did not show any activity with regard to PSA response. Due to insufficient PSA response, enrollment was stopped at the end of first stage per study design. The most significant severe toxicity was grade 3 fatigue. Further evaluation of 17-AAG at a dose of 300 mg/ m 2 i.v. weekly as a single agent in patients with metastatic, hormone-refractory prostate cancer who received at least one prior systemic therapy is not warranted.
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U2 - 10.1158/1078-0432.CCR-08-0221
DO - 10.1158/1078-0432.CCR-08-0221
M3 - Article
C2 - 19047126
AN - SCOPUS:59449108495
SN - 1078-0432
VL - 14
SP - 7940
EP - 7946
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 23
ER -