Platinum-based chemotherapy for variant castrate-resistant prostate cancer

Ana M. Aparicio, Andrea L. Harzstark, Paul G. Corn, Sijin Wen, John C. Araujo, Shi Ming Tu, Lance C. Pagliaro, Jeri Kim, Randall E. Millikan, Charles Ryan, Nizar M. Tannir, Amado J. Zurita, Paul Mathew, Wadih Arap, Patricia Troncoso, Peter F. Thall, Christopher J. Logothetis

Research output: Contribution to journalArticle

174 Citations (Scopus)

Abstract

Purpose: Clinical features characteristic of small-cell prostate carcinoma (SCPC), "anaplastic," often emerge during the progression of prostate cancer. We sought to determine the efficacy of platinum-based chemotherapy in patients meeting at least one of seven prospectively defined "anaplastic" clinical criteria, including exclusive visceral or predominantly lytic bone metastases, bulky tumor masses, low prostatespecific antigen levels relative to tumor burden, or short response to androgen deprivation therapy. Experimental Design: A 120-patient phase II trial of first-line carboplatin and docetaxel (CD) and second-line etoposide and cisplatin (EP) was designed to provide reliable clinical response estimates under a Bayesian probability model with early stopping rules in place for futility and toxicity. Results: Seventy-four of 113 (65.4%) and 24 of 71 (33.8%) were progression free after four cycles of CD and EP, respectively. Median overall survival (OS) was 16 months [95% confidence interval (CI), 13.6-19.0 months]. Of the seven "anaplastic" criteria, bulky tumor mass was significantly associated with poor outcome. Lactic acid dehydrogenase strongly predicted for OS and rapid progression. Serum carcinoembryonic antigen (CEA) concentration strongly predicted OS but not rapid progression. Neuroendocrine markers did not predict outcome or response to therapy. Conclusion: Our findings support the hypothesis that patients with "anaplastic" prostate cancer are a recognizable subset characterized by a high response rate of short duration to platinum-containing chemotherapies, similar to SCPC. Our results suggest that CEA is useful for selecting therapy in men with castration-resistant prostate cancer and consolidative therapies to bulky high-grade tumor masses should be considered in this patient population.

Original languageEnglish (US)
Pages (from-to)3621-3630
Number of pages10
JournalClinical Cancer Research
Volume19
Issue number13
DOIs
StatePublished - Jul 1 2013
Externally publishedYes

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docetaxel
Platinum
Prostatic Neoplasms
Drug Therapy
Small Cell Carcinoma
Carboplatin
Carcinoembryonic Antigen
Survival
Prostate
Medical Futility
Neoplasms
Castration
Etoposide
Therapeutics
Tumor Burden
Cisplatin
Androgens
Lactic Acid
Oxidoreductases
Research Design

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Aparicio, A. M., Harzstark, A. L., Corn, P. G., Wen, S., Araujo, J. C., Tu, S. M., ... Logothetis, C. J. (2013). Platinum-based chemotherapy for variant castrate-resistant prostate cancer. Clinical Cancer Research, 19(13), 3621-3630. https://doi.org/10.1158/1078-0432.CCR-12-3791

Platinum-based chemotherapy for variant castrate-resistant prostate cancer. / Aparicio, Ana M.; Harzstark, Andrea L.; Corn, Paul G.; Wen, Sijin; Araujo, John C.; Tu, Shi Ming; Pagliaro, Lance C.; Kim, Jeri; Millikan, Randall E.; Ryan, Charles; Tannir, Nizar M.; Zurita, Amado J.; Mathew, Paul; Arap, Wadih; Troncoso, Patricia; Thall, Peter F.; Logothetis, Christopher J.

In: Clinical Cancer Research, Vol. 19, No. 13, 01.07.2013, p. 3621-3630.

Research output: Contribution to journalArticle

Aparicio, AM, Harzstark, AL, Corn, PG, Wen, S, Araujo, JC, Tu, SM, Pagliaro, LC, Kim, J, Millikan, RE, Ryan, C, Tannir, NM, Zurita, AJ, Mathew, P, Arap, W, Troncoso, P, Thall, PF & Logothetis, CJ 2013, 'Platinum-based chemotherapy for variant castrate-resistant prostate cancer', Clinical Cancer Research, vol. 19, no. 13, pp. 3621-3630. https://doi.org/10.1158/1078-0432.CCR-12-3791
Aparicio AM, Harzstark AL, Corn PG, Wen S, Araujo JC, Tu SM et al. Platinum-based chemotherapy for variant castrate-resistant prostate cancer. Clinical Cancer Research. 2013 Jul 1;19(13):3621-3630. https://doi.org/10.1158/1078-0432.CCR-12-3791
Aparicio, Ana M. ; Harzstark, Andrea L. ; Corn, Paul G. ; Wen, Sijin ; Araujo, John C. ; Tu, Shi Ming ; Pagliaro, Lance C. ; Kim, Jeri ; Millikan, Randall E. ; Ryan, Charles ; Tannir, Nizar M. ; Zurita, Amado J. ; Mathew, Paul ; Arap, Wadih ; Troncoso, Patricia ; Thall, Peter F. ; Logothetis, Christopher J. / Platinum-based chemotherapy for variant castrate-resistant prostate cancer. In: Clinical Cancer Research. 2013 ; Vol. 19, No. 13. pp. 3621-3630.
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