A phase II study of pemetrexed as second-line chemotherapy for the treatment of metastatic castrate-resistant prostate cancer (CRPC); Hoosier Oncology Group GU03-67

N. M. Hahn, R. T. Zon, M. Yu, F. O. Ademuyiwa, T. Jones, W. Dugan, C. Whalen, R. Shanmugam, Todd Skaar, Chris J. Sweeney

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: No standard therapy exists for post-docetaxel castrate-resistant prostate cancer (CRPC) patients. This trial aimed to determine the safety and efficacy of pemetrexed in post-docetaxel CRPC patients. Materials and methods: CRPC patients with progression after docetaxel (Taxotere) therapy received pemetrexed (500 mg/m2) i.v. every 3 weeks. The primary end point was prostate-specific antigen (PSA) response. A pharmacogenetic analysis of the reduced folate carrier-1 gene (RFC1) G80A polymorphism was also carried out. Results: Forty-nine patients were enrolled: median age 68 years, median baseline PSA 72 ng/ml, and median Karnofsky performance status of 90. Grade 3 or 4 toxicity occurred in 20 (43%) and four patients (8%), respectively. Confirmed >50% PSA decline occurred in four patients (8%), stable PSA lasting at least 12 weeks in 10 patients (20%). A significant relationship was observed between time from prior docetaxel therapy and overall survival. Pharmacogenetic analyses of RFC1 G80A genotype frequencies showed no relationship between genotypes and clinical efficacy. Conclusions: Pemetrexed treatment of CRPC patients after docetaxel therapy was associated with only modest clinical activity. Further investigation of pemetrexed as a single agent in a nonenriched CRPC population is unlikely to add significant clinical benefit over that seen with traditional second-line chemotherapy agents such as mitoxantrone.

Original languageEnglish
Pages (from-to)1971-1976
Number of pages6
JournalAnnals of Oncology
Volume20
Issue number12
DOIs
StatePublished - 2009

Fingerprint

Pemetrexed
docetaxel
Prostatic Neoplasms
Drug Therapy
Prostate-Specific Antigen
Reduced Folate Carrier Protein
Therapeutics
Genotype
Karnofsky Performance Status
Mitoxantrone
Genes

Keywords

  • Castrate resistant
  • Pemetrexed
  • Pharmacogenomics
  • Post-docetaxel
  • Prostate cancer
  • Second line

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

A phase II study of pemetrexed as second-line chemotherapy for the treatment of metastatic castrate-resistant prostate cancer (CRPC); Hoosier Oncology Group GU03-67. / Hahn, N. M.; Zon, R. T.; Yu, M.; Ademuyiwa, F. O.; Jones, T.; Dugan, W.; Whalen, C.; Shanmugam, R.; Skaar, Todd; Sweeney, Chris J.

In: Annals of Oncology, Vol. 20, No. 12, 2009, p. 1971-1976.

Research output: Contribution to journalArticle

Hahn, N. M. ; Zon, R. T. ; Yu, M. ; Ademuyiwa, F. O. ; Jones, T. ; Dugan, W. ; Whalen, C. ; Shanmugam, R. ; Skaar, Todd ; Sweeney, Chris J. / A phase II study of pemetrexed as second-line chemotherapy for the treatment of metastatic castrate-resistant prostate cancer (CRPC); Hoosier Oncology Group GU03-67. In: Annals of Oncology. 2009 ; Vol. 20, No. 12. pp. 1971-1976.
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title = "A phase II study of pemetrexed as second-line chemotherapy for the treatment of metastatic castrate-resistant prostate cancer (CRPC); Hoosier Oncology Group GU03-67",
abstract = "Background: No standard therapy exists for post-docetaxel castrate-resistant prostate cancer (CRPC) patients. This trial aimed to determine the safety and efficacy of pemetrexed in post-docetaxel CRPC patients. Materials and methods: CRPC patients with progression after docetaxel (Taxotere) therapy received pemetrexed (500 mg/m2) i.v. every 3 weeks. The primary end point was prostate-specific antigen (PSA) response. A pharmacogenetic analysis of the reduced folate carrier-1 gene (RFC1) G80A polymorphism was also carried out. Results: Forty-nine patients were enrolled: median age 68 years, median baseline PSA 72 ng/ml, and median Karnofsky performance status of 90. Grade 3 or 4 toxicity occurred in 20 (43{\%}) and four patients (8{\%}), respectively. Confirmed >50{\%} PSA decline occurred in four patients (8{\%}), stable PSA lasting at least 12 weeks in 10 patients (20{\%}). A significant relationship was observed between time from prior docetaxel therapy and overall survival. Pharmacogenetic analyses of RFC1 G80A genotype frequencies showed no relationship between genotypes and clinical efficacy. Conclusions: Pemetrexed treatment of CRPC patients after docetaxel therapy was associated with only modest clinical activity. Further investigation of pemetrexed as a single agent in a nonenriched CRPC population is unlikely to add significant clinical benefit over that seen with traditional second-line chemotherapy agents such as mitoxantrone.",
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AU - Hahn, N. M.

AU - Zon, R. T.

AU - Yu, M.

AU - Ademuyiwa, F. O.

AU - Jones, T.

AU - Dugan, W.

AU - Whalen, C.

AU - Shanmugam, R.

AU - Skaar, Todd

AU - Sweeney, Chris J.

PY - 2009

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N2 - Background: No standard therapy exists for post-docetaxel castrate-resistant prostate cancer (CRPC) patients. This trial aimed to determine the safety and efficacy of pemetrexed in post-docetaxel CRPC patients. Materials and methods: CRPC patients with progression after docetaxel (Taxotere) therapy received pemetrexed (500 mg/m2) i.v. every 3 weeks. The primary end point was prostate-specific antigen (PSA) response. A pharmacogenetic analysis of the reduced folate carrier-1 gene (RFC1) G80A polymorphism was also carried out. Results: Forty-nine patients were enrolled: median age 68 years, median baseline PSA 72 ng/ml, and median Karnofsky performance status of 90. Grade 3 or 4 toxicity occurred in 20 (43%) and four patients (8%), respectively. Confirmed >50% PSA decline occurred in four patients (8%), stable PSA lasting at least 12 weeks in 10 patients (20%). A significant relationship was observed between time from prior docetaxel therapy and overall survival. Pharmacogenetic analyses of RFC1 G80A genotype frequencies showed no relationship between genotypes and clinical efficacy. Conclusions: Pemetrexed treatment of CRPC patients after docetaxel therapy was associated with only modest clinical activity. Further investigation of pemetrexed as a single agent in a nonenriched CRPC population is unlikely to add significant clinical benefit over that seen with traditional second-line chemotherapy agents such as mitoxantrone.

AB - Background: No standard therapy exists for post-docetaxel castrate-resistant prostate cancer (CRPC) patients. This trial aimed to determine the safety and efficacy of pemetrexed in post-docetaxel CRPC patients. Materials and methods: CRPC patients with progression after docetaxel (Taxotere) therapy received pemetrexed (500 mg/m2) i.v. every 3 weeks. The primary end point was prostate-specific antigen (PSA) response. A pharmacogenetic analysis of the reduced folate carrier-1 gene (RFC1) G80A polymorphism was also carried out. Results: Forty-nine patients were enrolled: median age 68 years, median baseline PSA 72 ng/ml, and median Karnofsky performance status of 90. Grade 3 or 4 toxicity occurred in 20 (43%) and four patients (8%), respectively. Confirmed >50% PSA decline occurred in four patients (8%), stable PSA lasting at least 12 weeks in 10 patients (20%). A significant relationship was observed between time from prior docetaxel therapy and overall survival. Pharmacogenetic analyses of RFC1 G80A genotype frequencies showed no relationship between genotypes and clinical efficacy. Conclusions: Pemetrexed treatment of CRPC patients after docetaxel therapy was associated with only modest clinical activity. Further investigation of pemetrexed as a single agent in a nonenriched CRPC population is unlikely to add significant clinical benefit over that seen with traditional second-line chemotherapy agents such as mitoxantrone.

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KW - Pemetrexed

KW - Pharmacogenomics

KW - Post-docetaxel

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KW - Second line

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