Phase II study on the addition of ASA404 (vadimezan; 5,6- dimethylxanthenone-4-acetic acid) to docetaxel in CRMPC

Roberto Pili, Mark A. Rosenthal, Paul N. Mainwaring, Guy Van Hazel, Sandy Srinivas, Robert Dreicer, Sanjay Goel, Joseph Leach, Shirley Wong, Peter Clingan

Research output: Contribution to journalArticle

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Abstract

Purpose: This randomized phase II study evaluated ASA404 (vadimezan; 5,6-dimethylxanthenone-4-acetic acid) in combination with docetaxel in castration-refractory metastatic prostate cancer (CRMPC). Experimental Design: Seventy-four patients with histopathologically confirmed CRMPC previously untreated with chemotherapy were randomized to receive either ≤10 cycles of docetaxel 75 mg/m2 alone (D; n = 39) or docetaxel plus ASA404 1,200 mg/m2 (A-D; n = 35). Study endpoints included prostate-specific antigen response, tumor response, median time to tumor progression, median survival, and toxicity. Results: The overall pattern of adverse events was similar in the two groups; however, there was a higher incidence of cardiac adverse events and neutropenia in the A-D group. Coadministration of ASA404 with docetaxel did not affect total systemic exposure of either drug. A higher prostate-specific antigen response rate was reported with A-D versus D (59.4% versus 36.8%), together with a larger median percentage reduction in prostate-specific antigen (84.0% versus 61.9%) and a shorter median time to prostate-specific antigen nadir (105 versus 119 d). Tumor response rate was 23.1% with A-D and 9.1% with D. Time to tumor progression and median survival were similar in the groups (time to tumor progression, 8.7 mo for A-D and 8.4 mo for D; survival, 17.0 mo for A-D and 17.2 mo for D). Hazard ratios for time to tumor progression and survival were 0.81 and 0.80, respectively, favoring A-D; 2-year survival was 33.3% with A-D and 22.8% with D. Conclusion: The study met some endpoints (prostate-specific antigen response, tumor response) but not others (i.e., time to tumor progression). The results indicate that the combination of ASA404 with docetaxel has acceptable toxicity, lacks adverse pharmacokinetic interaction, and, overall, has activity in CRMPC.

Original languageEnglish (US)
Pages (from-to)2906-2914
Number of pages9
JournalClinical Cancer Research
Volume16
Issue number10
DOIs
StatePublished - May 15 2010

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vadimezan
docetaxel
Castration
Prostatic Neoplasms
Prostate-Specific Antigen
Neoplasms
Survival
Neutropenia

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pili, R., Rosenthal, M. A., Mainwaring, P. N., Van Hazel, G., Srinivas, S., Dreicer, R., ... Clingan, P. (2010). Phase II study on the addition of ASA404 (vadimezan; 5,6- dimethylxanthenone-4-acetic acid) to docetaxel in CRMPC. Clinical Cancer Research, 16(10), 2906-2914. https://doi.org/10.1158/1078-0432.CCR-09-3026

Phase II study on the addition of ASA404 (vadimezan; 5,6- dimethylxanthenone-4-acetic acid) to docetaxel in CRMPC. / Pili, Roberto; Rosenthal, Mark A.; Mainwaring, Paul N.; Van Hazel, Guy; Srinivas, Sandy; Dreicer, Robert; Goel, Sanjay; Leach, Joseph; Wong, Shirley; Clingan, Peter.

In: Clinical Cancer Research, Vol. 16, No. 10, 15.05.2010, p. 2906-2914.

Research output: Contribution to journalArticle

Pili, R, Rosenthal, MA, Mainwaring, PN, Van Hazel, G, Srinivas, S, Dreicer, R, Goel, S, Leach, J, Wong, S & Clingan, P 2010, 'Phase II study on the addition of ASA404 (vadimezan; 5,6- dimethylxanthenone-4-acetic acid) to docetaxel in CRMPC', Clinical Cancer Research, vol. 16, no. 10, pp. 2906-2914. https://doi.org/10.1158/1078-0432.CCR-09-3026
Pili, Roberto ; Rosenthal, Mark A. ; Mainwaring, Paul N. ; Van Hazel, Guy ; Srinivas, Sandy ; Dreicer, Robert ; Goel, Sanjay ; Leach, Joseph ; Wong, Shirley ; Clingan, Peter. / Phase II study on the addition of ASA404 (vadimezan; 5,6- dimethylxanthenone-4-acetic acid) to docetaxel in CRMPC. In: Clinical Cancer Research. 2010 ; Vol. 16, No. 10. pp. 2906-2914.
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abstract = "Purpose: This randomized phase II study evaluated ASA404 (vadimezan; 5,6-dimethylxanthenone-4-acetic acid) in combination with docetaxel in castration-refractory metastatic prostate cancer (CRMPC). Experimental Design: Seventy-four patients with histopathologically confirmed CRMPC previously untreated with chemotherapy were randomized to receive either ≤10 cycles of docetaxel 75 mg/m2 alone (D; n = 39) or docetaxel plus ASA404 1,200 mg/m2 (A-D; n = 35). Study endpoints included prostate-specific antigen response, tumor response, median time to tumor progression, median survival, and toxicity. Results: The overall pattern of adverse events was similar in the two groups; however, there was a higher incidence of cardiac adverse events and neutropenia in the A-D group. Coadministration of ASA404 with docetaxel did not affect total systemic exposure of either drug. A higher prostate-specific antigen response rate was reported with A-D versus D (59.4{\%} versus 36.8{\%}), together with a larger median percentage reduction in prostate-specific antigen (84.0{\%} versus 61.9{\%}) and a shorter median time to prostate-specific antigen nadir (105 versus 119 d). Tumor response rate was 23.1{\%} with A-D and 9.1{\%} with D. Time to tumor progression and median survival were similar in the groups (time to tumor progression, 8.7 mo for A-D and 8.4 mo for D; survival, 17.0 mo for A-D and 17.2 mo for D). Hazard ratios for time to tumor progression and survival were 0.81 and 0.80, respectively, favoring A-D; 2-year survival was 33.3{\%} with A-D and 22.8{\%} with D. Conclusion: The study met some endpoints (prostate-specific antigen response, tumor response) but not others (i.e., time to tumor progression). The results indicate that the combination of ASA404 with docetaxel has acceptable toxicity, lacks adverse pharmacokinetic interaction, and, overall, has activity in CRMPC.",
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AU - Mainwaring, Paul N.

AU - Van Hazel, Guy

AU - Srinivas, Sandy

AU - Dreicer, Robert

AU - Goel, Sanjay

AU - Leach, Joseph

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AU - Clingan, Peter

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N2 - Purpose: This randomized phase II study evaluated ASA404 (vadimezan; 5,6-dimethylxanthenone-4-acetic acid) in combination with docetaxel in castration-refractory metastatic prostate cancer (CRMPC). Experimental Design: Seventy-four patients with histopathologically confirmed CRMPC previously untreated with chemotherapy were randomized to receive either ≤10 cycles of docetaxel 75 mg/m2 alone (D; n = 39) or docetaxel plus ASA404 1,200 mg/m2 (A-D; n = 35). Study endpoints included prostate-specific antigen response, tumor response, median time to tumor progression, median survival, and toxicity. Results: The overall pattern of adverse events was similar in the two groups; however, there was a higher incidence of cardiac adverse events and neutropenia in the A-D group. Coadministration of ASA404 with docetaxel did not affect total systemic exposure of either drug. A higher prostate-specific antigen response rate was reported with A-D versus D (59.4% versus 36.8%), together with a larger median percentage reduction in prostate-specific antigen (84.0% versus 61.9%) and a shorter median time to prostate-specific antigen nadir (105 versus 119 d). Tumor response rate was 23.1% with A-D and 9.1% with D. Time to tumor progression and median survival were similar in the groups (time to tumor progression, 8.7 mo for A-D and 8.4 mo for D; survival, 17.0 mo for A-D and 17.2 mo for D). Hazard ratios for time to tumor progression and survival were 0.81 and 0.80, respectively, favoring A-D; 2-year survival was 33.3% with A-D and 22.8% with D. Conclusion: The study met some endpoints (prostate-specific antigen response, tumor response) but not others (i.e., time to tumor progression). The results indicate that the combination of ASA404 with docetaxel has acceptable toxicity, lacks adverse pharmacokinetic interaction, and, overall, has activity in CRMPC.

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