A Phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with hormone-refractory metastatic prostate cancer

Elisabeth I. Heath, David W. Hillman, Ulka Vaishampayan, Shijie Sheng, Fazlul Sarkar, Felicity Harper, Melvin Gaskins, Henry C. Pitot, Winston Tan, S. Percy Ivy, Roberto Pili, Michael A. Carducci, Charles Erlichman, Glenn Liu

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7940-7946
Number of pages7
JournalClinical Cancer Research
Volume14
Issue number23
DOIs
StatePublished - Dec 1 2008
Externally publishedYes

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tanespimycin
Prostatic Neoplasms
Prostate-Specific Antigen
Hormones
Fatigue
Rifabutin
Confidence Intervals
Lymphopenia
Survival
Proxy
Interleukin-8
Heterografts
Disease-Free Survival
Interleukin-6

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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A Phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with hormone-refractory metastatic prostate cancer. / Heath, Elisabeth I.; Hillman, David W.; Vaishampayan, Ulka; Sheng, Shijie; Sarkar, Fazlul; Harper, Felicity; Gaskins, Melvin; Pitot, Henry C.; Tan, Winston; Ivy, S. Percy; Pili, Roberto; Carducci, Michael A.; Erlichman, Charles; Liu, Glenn.

In: Clinical Cancer Research, Vol. 14, No. 23, 01.12.2008, p. 7940-7946.

Research output: Contribution to journalArticle

Heath, EI, Hillman, DW, Vaishampayan, U, Sheng, S, Sarkar, F, Harper, F, Gaskins, M, Pitot, HC, Tan, W, Ivy, SP, Pili, R, Carducci, MA, Erlichman, C & Liu, G 2008, 'A Phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with hormone-refractory metastatic prostate cancer', Clinical Cancer Research, vol. 14, no. 23, pp. 7940-7946. https://doi.org/10.1158/1078-0432.CCR-08-0221
Heath, Elisabeth I. ; Hillman, David W. ; Vaishampayan, Ulka ; Sheng, Shijie ; Sarkar, Fazlul ; Harper, Felicity ; Gaskins, Melvin ; Pitot, Henry C. ; Tan, Winston ; Ivy, S. Percy ; Pili, Roberto ; Carducci, Michael A. ; Erlichman, Charles ; Liu, Glenn. / A Phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with hormone-refractory metastatic prostate cancer. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 23. pp. 7940-7946.
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abstract = "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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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

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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.

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