Oral Fenretinide in biochemically recurrent prostate cancer: A California cancer consortium phase II trial

Eric Cheung, Jacek Pinski, Tanya Dorff, Susan Groshen, David I. Quinn, C. Patrick Reynolds, Barry J. Maurer, Primo N Lara, Denice D. Tsao-Wei, Przemyslaw Twardowski, Gurkamal Chatta, Mark McNamara, David R Gandara

Research output: Contribution to journalArticle

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Abstract

Background: Fenretinide is a synthetic retinoid that is cytotoxic to a variety of cancers. We conducted a phase II trial of oral fenretinide in patients with biochemically recurrent prostate cancer. Patients and Methods: Eligible patients had histologically confirmed prostate cancer and a confirmed rising prostate-specific antigen (PSA) ≥ 2 ng/mL following either radical prostatectomy and/or pelvic radiation therapy, without clinical or radiographic evidence of metastasis. The primary endpoint was PSA response, which was defined as a confirmed decrease by ≥ 50%, and ≥ 5 ng/mL, from the pretreatment value. Treatment comprised oral fenretinide 900 mg/m 2 twice daily for 1 week, every 3 weeks, for 1 year. Results: After a median follow-up of 17.7 months, out of 23 patients, 7 (30%) patients had PSA stable disease (SD), 11 (48%) patients had PSA progression within 3 months, 4 patients had minimal increases over 3 months that did not qualify as SD or progression (17%), and one patient (4%) was not evaluable. Median time to PSA progression was 4.6 months (95% Cl, 3.2-8.2 months). Observed grade 3 toxicities included fatigue, pain, hypermagnesemia, a rise in lipase, and nyctalopia. Conclusion: Although well-tolerated, oral fenretinide did not meet prespecified PSA criteria for response in biochemically recurrent prostate cancer; however, 30% of patients had SD, which suggests modest single-agent clinical activity. The role of different formulations of fenretinide, which might allow for higher serum concentrations of the drug, is currently under investigation.

Original languageEnglish (US)
Pages (from-to)43-50
Number of pages8
JournalClinical Genitourinary Cancer
Volume7
Issue number1
DOIs
StatePublished - 2009

Fingerprint

Fenretinide
Prostatic Neoplasms
Prostate-Specific Antigen
Neoplasms
Night Blindness
Retinoids
Prostatectomy
Lipase
Fatigue
Disease Progression
Radiotherapy
Neoplasm Metastasis

Keywords

  • 4-HPR
  • Alanine aminotransferase
  • Aspartate aminotransferase
  • Prostate-specific antigen

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Oral Fenretinide in biochemically recurrent prostate cancer : A California cancer consortium phase II trial. / Cheung, Eric; Pinski, Jacek; Dorff, Tanya; Groshen, Susan; Quinn, David I.; Reynolds, C. Patrick; Maurer, Barry J.; Lara, Primo N; Tsao-Wei, Denice D.; Twardowski, Przemyslaw; Chatta, Gurkamal; McNamara, Mark; Gandara, David R.

In: Clinical Genitourinary Cancer, Vol. 7, No. 1, 2009, p. 43-50.

Research output: Contribution to journalArticle

Cheung, E, Pinski, J, Dorff, T, Groshen, S, Quinn, DI, Reynolds, CP, Maurer, BJ, Lara, PN, Tsao-Wei, DD, Twardowski, P, Chatta, G, McNamara, M & Gandara, DR 2009, 'Oral Fenretinide in biochemically recurrent prostate cancer: A California cancer consortium phase II trial', Clinical Genitourinary Cancer, vol. 7, no. 1, pp. 43-50. https://doi.org/10.3816/CGC.2009.n.008
Cheung, Eric ; Pinski, Jacek ; Dorff, Tanya ; Groshen, Susan ; Quinn, David I. ; Reynolds, C. Patrick ; Maurer, Barry J. ; Lara, Primo N ; Tsao-Wei, Denice D. ; Twardowski, Przemyslaw ; Chatta, Gurkamal ; McNamara, Mark ; Gandara, David R. / Oral Fenretinide in biochemically recurrent prostate cancer : A California cancer consortium phase II trial. In: Clinical Genitourinary Cancer. 2009 ; Vol. 7, No. 1. pp. 43-50.
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abstract = "Background: Fenretinide is a synthetic retinoid that is cytotoxic to a variety of cancers. We conducted a phase II trial of oral fenretinide in patients with biochemically recurrent prostate cancer. Patients and Methods: Eligible patients had histologically confirmed prostate cancer and a confirmed rising prostate-specific antigen (PSA) ≥ 2 ng/mL following either radical prostatectomy and/or pelvic radiation therapy, without clinical or radiographic evidence of metastasis. The primary endpoint was PSA response, which was defined as a confirmed decrease by ≥ 50{\%}, and ≥ 5 ng/mL, from the pretreatment value. Treatment comprised oral fenretinide 900 mg/m 2 twice daily for 1 week, every 3 weeks, for 1 year. Results: After a median follow-up of 17.7 months, out of 23 patients, 7 (30{\%}) patients had PSA stable disease (SD), 11 (48{\%}) patients had PSA progression within 3 months, 4 patients had minimal increases over 3 months that did not qualify as SD or progression (17{\%}), and one patient (4{\%}) was not evaluable. Median time to PSA progression was 4.6 months (95{\%} Cl, 3.2-8.2 months). Observed grade 3 toxicities included fatigue, pain, hypermagnesemia, a rise in lipase, and nyctalopia. Conclusion: Although well-tolerated, oral fenretinide did not meet prespecified PSA criteria for response in biochemically recurrent prostate cancer; however, 30{\%} of patients had SD, which suggests modest single-agent clinical activity. The role of different formulations of fenretinide, which might allow for higher serum concentrations of the drug, is currently under investigation.",
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AU - Quinn, David I.

AU - Reynolds, C. Patrick

AU - Maurer, Barry J.

AU - Lara, Primo N

AU - Tsao-Wei, Denice D.

AU - Twardowski, Przemyslaw

AU - Chatta, Gurkamal

AU - McNamara, Mark

AU - Gandara, David R

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N2 - Background: Fenretinide is a synthetic retinoid that is cytotoxic to a variety of cancers. We conducted a phase II trial of oral fenretinide in patients with biochemically recurrent prostate cancer. Patients and Methods: Eligible patients had histologically confirmed prostate cancer and a confirmed rising prostate-specific antigen (PSA) ≥ 2 ng/mL following either radical prostatectomy and/or pelvic radiation therapy, without clinical or radiographic evidence of metastasis. The primary endpoint was PSA response, which was defined as a confirmed decrease by ≥ 50%, and ≥ 5 ng/mL, from the pretreatment value. Treatment comprised oral fenretinide 900 mg/m 2 twice daily for 1 week, every 3 weeks, for 1 year. Results: After a median follow-up of 17.7 months, out of 23 patients, 7 (30%) patients had PSA stable disease (SD), 11 (48%) patients had PSA progression within 3 months, 4 patients had minimal increases over 3 months that did not qualify as SD or progression (17%), and one patient (4%) was not evaluable. Median time to PSA progression was 4.6 months (95% Cl, 3.2-8.2 months). Observed grade 3 toxicities included fatigue, pain, hypermagnesemia, a rise in lipase, and nyctalopia. Conclusion: Although well-tolerated, oral fenretinide did not meet prespecified PSA criteria for response in biochemically recurrent prostate cancer; however, 30% of patients had SD, which suggests modest single-agent clinical activity. The role of different formulations of fenretinide, which might allow for higher serum concentrations of the drug, is currently under investigation.

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KW - 4-HPR

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KW - Aspartate aminotransferase

KW - Prostate-specific antigen

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