Phase II Study of Imatinib Mesylate in Patients with Prostate Cancer with Evidence of Biochemical Relapse After Definitive Radical Retropubic Prostatectomy or Radiotherapy

Gopal K. Bajaj, Zhe Zhang, Elizabeth Garrett-Mayer, Renee Drew, Victoria Sinibaldi, Roberto Pili, Samuel R. Denmeade, Michael A. Carducci, Mario A. Eisenberger, Theodore L. DeWeese

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Objectives: Patients with biochemical recurrence of prostate cancer after definitive or salvage local therapy in the absence of metastatic disease represent a group well suited to a novel therapeutic intervention. Imatinib mesylate (Gleevec) is a protein-tyrosine kinase inhibitor that has previously been tested in men with androgen-independent and metastatic prostate cancer. This Phase II study was undertaken to determine the safety and efficacy of imatinib mesylate in men with biochemical relapse of nonmetastatic, androgen-sensitive prostate cancer after local therapy. Methods: Twenty-seven patients were treated with imatinib mesylate 400 mg twice daily for up to 12 months. Three patients (11%) completed less than 4 weeks of therapy and were included in the intent-to-treat analysis of the response to therapy. Results: Of the 27 patients treated, 5 (18.5%) had a stable prostate-specific antigen (PSA) during the course of treatment; 2 patients (7.4%) experienced a partial response. The remaining 20 patients (74.1%) demonstrated PSA progression. The median progression-free survival was 3 months. The proportion of patients achieving a partial PSA response during therapy did not significantly differ from the null rate of 5% (P = 0.394). Seven patients (25.9%) discontinued therapy secondary to grade 1 to 3 toxicities. No irreversible National Institutes of Health Common Toxicity Criteria grade 3 or 4 toxicities occurred. Grade 3 and 4 toxicity included leukopenia (3.7%), serum glutamic-oxaloacetic transaminase (3.7%) and serum glutamic-pyruvic transaminase (3.7%) elevation, and rash (18.5%). Conclusions: The results of our study have demonstrated that imatinib mesylate delivered at a dose of 400 mg twice daily is associated with a moderate degree of toxicity and a limited PSA response in this patient population.

Original languageEnglish (US)
Pages (from-to)526-531
Number of pages6
JournalUrology
Volume69
Issue number3
DOIs
StatePublished - Mar 2007
Externally publishedYes

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Prostatectomy
Prostatic Neoplasms
Radiotherapy
Recurrence
Prostate-Specific Antigen
Therapeutics
Androgens
Imatinib Mesylate
Salvage Therapy
National Institutes of Health (U.S.)
Leukopenia
Protein Kinase Inhibitors
Aspartate Aminotransferases
Exanthema
Alanine Transaminase
Protein-Tyrosine Kinases
Disease-Free Survival
Safety
Serum

ASJC Scopus subject areas

  • Urology

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Phase II Study of Imatinib Mesylate in Patients with Prostate Cancer with Evidence of Biochemical Relapse After Definitive Radical Retropubic Prostatectomy or Radiotherapy. / Bajaj, Gopal K.; Zhang, Zhe; Garrett-Mayer, Elizabeth; Drew, Renee; Sinibaldi, Victoria; Pili, Roberto; Denmeade, Samuel R.; Carducci, Michael A.; Eisenberger, Mario A.; DeWeese, Theodore L.

In: Urology, Vol. 69, No. 3, 03.2007, p. 526-531.

Research output: Contribution to journalArticle

Bajaj, GK, Zhang, Z, Garrett-Mayer, E, Drew, R, Sinibaldi, V, Pili, R, Denmeade, SR, Carducci, MA, Eisenberger, MA & DeWeese, TL 2007, 'Phase II Study of Imatinib Mesylate in Patients with Prostate Cancer with Evidence of Biochemical Relapse After Definitive Radical Retropubic Prostatectomy or Radiotherapy', Urology, vol. 69, no. 3, pp. 526-531. https://doi.org/10.1016/j.urology.2006.12.006
Bajaj, Gopal K. ; Zhang, Zhe ; Garrett-Mayer, Elizabeth ; Drew, Renee ; Sinibaldi, Victoria ; Pili, Roberto ; Denmeade, Samuel R. ; Carducci, Michael A. ; Eisenberger, Mario A. ; DeWeese, Theodore L. / Phase II Study of Imatinib Mesylate in Patients with Prostate Cancer with Evidence of Biochemical Relapse After Definitive Radical Retropubic Prostatectomy or Radiotherapy. In: Urology. 2007 ; Vol. 69, No. 3. pp. 526-531.
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abstract = "Objectives: Patients with biochemical recurrence of prostate cancer after definitive or salvage local therapy in the absence of metastatic disease represent a group well suited to a novel therapeutic intervention. Imatinib mesylate (Gleevec) is a protein-tyrosine kinase inhibitor that has previously been tested in men with androgen-independent and metastatic prostate cancer. This Phase II study was undertaken to determine the safety and efficacy of imatinib mesylate in men with biochemical relapse of nonmetastatic, androgen-sensitive prostate cancer after local therapy. Methods: Twenty-seven patients were treated with imatinib mesylate 400 mg twice daily for up to 12 months. Three patients (11{\%}) completed less than 4 weeks of therapy and were included in the intent-to-treat analysis of the response to therapy. Results: Of the 27 patients treated, 5 (18.5{\%}) had a stable prostate-specific antigen (PSA) during the course of treatment; 2 patients (7.4{\%}) experienced a partial response. The remaining 20 patients (74.1{\%}) demonstrated PSA progression. The median progression-free survival was 3 months. The proportion of patients achieving a partial PSA response during therapy did not significantly differ from the null rate of 5{\%} (P = 0.394). Seven patients (25.9{\%}) discontinued therapy secondary to grade 1 to 3 toxicities. No irreversible National Institutes of Health Common Toxicity Criteria grade 3 or 4 toxicities occurred. Grade 3 and 4 toxicity included leukopenia (3.7{\%}), serum glutamic-oxaloacetic transaminase (3.7{\%}) and serum glutamic-pyruvic transaminase (3.7{\%}) elevation, and rash (18.5{\%}). Conclusions: The results of our study have demonstrated that imatinib mesylate delivered at a dose of 400 mg twice daily is associated with a moderate degree of toxicity and a limited PSA response in this patient population.",
author = "Bajaj, {Gopal K.} and Zhe Zhang and Elizabeth Garrett-Mayer and Renee Drew and Victoria Sinibaldi and Roberto Pili and Denmeade, {Samuel R.} and Carducci, {Michael A.} and Eisenberger, {Mario A.} and DeWeese, {Theodore L.}",
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T1 - Phase II Study of Imatinib Mesylate in Patients with Prostate Cancer with Evidence of Biochemical Relapse After Definitive Radical Retropubic Prostatectomy or Radiotherapy

AU - Bajaj, Gopal K.

AU - Zhang, Zhe

AU - Garrett-Mayer, Elizabeth

AU - Drew, Renee

AU - Sinibaldi, Victoria

AU - Pili, Roberto

AU - Denmeade, Samuel R.

AU - Carducci, Michael A.

AU - Eisenberger, Mario A.

AU - DeWeese, Theodore L.

PY - 2007/3

Y1 - 2007/3

N2 - Objectives: Patients with biochemical recurrence of prostate cancer after definitive or salvage local therapy in the absence of metastatic disease represent a group well suited to a novel therapeutic intervention. Imatinib mesylate (Gleevec) is a protein-tyrosine kinase inhibitor that has previously been tested in men with androgen-independent and metastatic prostate cancer. This Phase II study was undertaken to determine the safety and efficacy of imatinib mesylate in men with biochemical relapse of nonmetastatic, androgen-sensitive prostate cancer after local therapy. Methods: Twenty-seven patients were treated with imatinib mesylate 400 mg twice daily for up to 12 months. Three patients (11%) completed less than 4 weeks of therapy and were included in the intent-to-treat analysis of the response to therapy. Results: Of the 27 patients treated, 5 (18.5%) had a stable prostate-specific antigen (PSA) during the course of treatment; 2 patients (7.4%) experienced a partial response. The remaining 20 patients (74.1%) demonstrated PSA progression. The median progression-free survival was 3 months. The proportion of patients achieving a partial PSA response during therapy did not significantly differ from the null rate of 5% (P = 0.394). Seven patients (25.9%) discontinued therapy secondary to grade 1 to 3 toxicities. No irreversible National Institutes of Health Common Toxicity Criteria grade 3 or 4 toxicities occurred. Grade 3 and 4 toxicity included leukopenia (3.7%), serum glutamic-oxaloacetic transaminase (3.7%) and serum glutamic-pyruvic transaminase (3.7%) elevation, and rash (18.5%). Conclusions: The results of our study have demonstrated that imatinib mesylate delivered at a dose of 400 mg twice daily is associated with a moderate degree of toxicity and a limited PSA response in this patient population.

AB - Objectives: Patients with biochemical recurrence of prostate cancer after definitive or salvage local therapy in the absence of metastatic disease represent a group well suited to a novel therapeutic intervention. Imatinib mesylate (Gleevec) is a protein-tyrosine kinase inhibitor that has previously been tested in men with androgen-independent and metastatic prostate cancer. This Phase II study was undertaken to determine the safety and efficacy of imatinib mesylate in men with biochemical relapse of nonmetastatic, androgen-sensitive prostate cancer after local therapy. Methods: Twenty-seven patients were treated with imatinib mesylate 400 mg twice daily for up to 12 months. Three patients (11%) completed less than 4 weeks of therapy and were included in the intent-to-treat analysis of the response to therapy. Results: Of the 27 patients treated, 5 (18.5%) had a stable prostate-specific antigen (PSA) during the course of treatment; 2 patients (7.4%) experienced a partial response. The remaining 20 patients (74.1%) demonstrated PSA progression. The median progression-free survival was 3 months. The proportion of patients achieving a partial PSA response during therapy did not significantly differ from the null rate of 5% (P = 0.394). Seven patients (25.9%) discontinued therapy secondary to grade 1 to 3 toxicities. No irreversible National Institutes of Health Common Toxicity Criteria grade 3 or 4 toxicities occurred. Grade 3 and 4 toxicity included leukopenia (3.7%), serum glutamic-oxaloacetic transaminase (3.7%) and serum glutamic-pyruvic transaminase (3.7%) elevation, and rash (18.5%). Conclusions: The results of our study have demonstrated that imatinib mesylate delivered at a dose of 400 mg twice daily is associated with a moderate degree of toxicity and a limited PSA response in this patient population.

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