Intermittent chemotherapy as a platform for testing novel agents in patients with metastatic castration-resistant prostate cancer: A Department of Defense Prostate Cancer Clinical Trials Consortium randomized phase II trial of intermittent docetaxel with prednisone with or without maintenance GM-CSF

Rahul R. Aggarwal, Tomasz M. Beer, Vivian K. Weinberg, Celestia Higano, Mary Ellen Taplin, Charles J. Ryan, Amy M. Lin, Joshi Alumkal, Julie N. Graff, Luke T. Nordquist, Isheen Herrera, Eric J. Small

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5 Scopus citations

Abstract

Abstract Background Immunotherapy with granulocyte-macrophage colony-stimulating factor (GM-CSF), an agent that previously demonstrated antitumor activity, was evaluated within an intermittent chemotherapy framework of docetaxel with prednisone (D+P) in metastatic castration-resistant prostate cancer (mCRPC). Patients and Methods mCRPC patients with ≥ 50% prostate-specific antigen (PSA) decline after 6 cycles of D+P were randomized to either GM-CSF or observation (Obs). At disease progression (PD), D+P was reinitiated for 6 cycles followed by the same "off chemotherapy" regimen in patients eligible for chemotherapy interruption. The sequence was repeated until PD during chemotherapy, lack of PSA response to chemotherapy, or unacceptable toxicity. The primary end point was time to chemotherapy resistance (TTCR). Results Of 125 patients enrolled, 52 (42%) experienced ≥ 50% PSA decline on induction D+P and were randomized to GM-CSF (n = 27) or Obs (n = 25). The median time to PD was 3.3 months (95% confidence interval [CI], 2.4-3.5) and 1.5 months (95% CI, 1.5-2.4) during the initial course of GM-CSF and Obs, respectively. Twelve of 26 (46%) patients responded to a second course of D+P. Eleven randomized patients (21%) experienced PD during chemotherapy, precluding accurate assessment of TTCR. The remaining 41 randomized patients discontinued study for lack of PSA response to chemotherapy (n = 8), patient choice to not restart chemotherapy with PSA PD (n = 13), toxicity (n = 7), or study withdrawal (n = 13). Conclusion Conducting a prospective study in mCRPC with maintenance immunotherapy within the framework of intermittent chemotherapy was feasible. The use of PSA instead of radiographic end points limited the number of evaluable patients. This study provides important insight into designing contemporary intermittent chemotherapy trials with maintenance immunotherapy in patients with advanced prostate cancer.

Original languageEnglish (US)
Article number349
Pages (from-to)e191-e198
JournalClinical Genitourinary Cancer
Volume13
Issue number3
DOIs
StatePublished - Jun 1 2015

Bibliographical note

Funding Information:
Tomasz M. Beer has received research funding from Sanofi. The remaining authors have no conflicts of interest to disclose.

Publisher Copyright:
© 2015 Elsevier Inc.

Keywords

  • Granulocyte macrophage colony stimulating factor
  • Immunotherapy
  • Maintenance therapy
  • Prostatic neoplasm
  • Taxane-based chemotherapy

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