Multinational, double-blind, phase III study of prednisone and either satraplatin or placebo in patients with castrate-refractory prostate cancer progressing after prior chemotherapy: the SPARC trial.

Abstract

PURPOSE:

This multinational, double-blind, randomized, placebo-controlled, phase III trial assessed the efficacy and tolerability of the oral platinum analog satraplatin in patients with metastatic castrate-refractory prostate cancer (CRPC) experiencing progression after one prior chemotherapy regimen.

PATIENTS AND METHODS:

Nine hundred fifty patients were randomly assigned (2:1) to receive oral satraplatin (n = 635) 80 mg/m(2) on days 1 to 5 of a 35-day cycle and prednisone 5 mg twice daily or placebo (n = 315) and prednisone 5 mg twice daily. Primary end points were progression-free survival and overall survival (OS). The secondary end point was time to pain progression (TPP).

RESULTS:

A 33% reduction (hazard ratio [HR] = 0.67; 95% CI, 0.57 to 0.77; P < .001) was observed in the risk of progression or death with satraplatin versus placebo. This effect was maintained irrespective of prior docetaxel treatment. No difference in OS was seen between the satraplatin and placebo arms (HR = 0.98; 95% CI, 0.84 to 1.15; P = .80). Compared with placebo, satraplatin significantly reduced TPP (HR = 0.64; 95% CI, 0.51 to 0.79; P < .001). Satraplatin was generally well tolerated, although myelosuppression and GI disorders occurred more frequently with satraplatin.

CONCLUSION:

Oral satraplatin delayed progression of disease and pain in patients with metastatic CRPC experiencing progression after initial chemotherapy but did not provide a significant OS benefit. Satraplatin was generally well tolerated. These results suggest activity for satraplatin in patients with CRPC who experience progression after initial chemotherapy.

• Authors: Cora N Sternberg, Daniel P Petrylak, Oliver Sartor, J Alfred Witjes, Tomasz Demkow, Jean-Marc Ferrero, Jean-Christophe Eymard, Silvia Falcon, Fabio Calabrò, Nicholas James, Istvan Bodrogi, Peter Harper, Manfred Wirth, William Berry, Michael E Petrone, Thomas J McKearn, Mojtaba Noursalehi, Martine George, Marcel Rozencweig
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 27 Issue 32 Pg. 5431-8 (Nov 10 2009) ISSN: 1527-7755 [Electronic] United States
• PMID: 19805692 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Organoplatinum Compounds
• satraplatin
• Prednisone

Topics

• Administration, Oral
• Adult
• Aged
• Aged, 80 and over
• Anemia (chemically induced)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Constipation (chemically induced)
• Diarrhea (chemically induced)
• Disease Progression
• Double-Blind Method
• Drug Administration Schedule
• Humans
• Male
• Middle Aged
• Nausea (chemically induced)
• Neoplasm Metastasis
• Orchiectomy
• Organoplatinum Compounds (administration & dosage, adverse effects)
• Prednisone (administration & dosage, adverse effects)
• Prostatic Neoplasms (drug therapy, pathology, surgery)
• Survival Analysis
• Thrombocytopenia (chemically induced)
• Treatment Outcome