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

Clin Genitourin Cancer. 2015 Jun;13(3):e191-8. doi: 10.1016/j.clgc.2014.12.004. Epub 2014 Dec 9.


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.

Keywords: Granulocyte macrophage colony stimulating factor; Immunotherapy; Maintenance therapy; Prostatic neoplasm; Taxane-based chemotherapy.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Docetaxel
  • Drug Administration Schedule
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage*
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use
  • Humans
  • Maintenance Chemotherapy
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Prednisone / administration & dosage*
  • Prednisone / therapeutic use
  • Prospective Studies
  • Prostate-Specific Antigen / metabolism
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / metabolism
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Survival Analysis
  • Taxoids / administration & dosage*
  • Taxoids / therapeutic use
  • Treatment Outcome


  • Antineoplastic Agents
  • Taxoids
  • Docetaxel
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Prostate-Specific Antigen
  • Prednisone