Saracatinib as a metastasis inhibitor in metastatic castration-resistant prostate cancer: A University of Chicago Phase 2 Consortium and DOD/PCF Prostate Cancer Clinical Trials Consortium Study

Fyn is a kinase that is upregulated in a subset of metastatic castration-resistant prostate cancer. Saracatinib potently inhibits Fyn activation. We have noted a relationship between Fyn expression and directional motility, a cellular process related to metastasis.

As such we hypothesized that treatment with saracatinib would increase the time required to develop new metastatic lesions.

Patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel were eligible for enrollment. This study was executed as a randomized discontinuation trial. During a lead-in phase of two 28-Day cycles, all patients received saracatinib. Afterward, patients with radiographically stable disease were randomized to either saracatinib or placebo. Patients continued treatment until evidence of new metastasis.

Thirty-one patients were treated. Only 26% of patients had stable disease after 8 weeks and thus proceeded to randomization. This required early termination of the study for futility. The 70% of patients who progressed after the lead-in phase exhibited expansion of existing lesions or decompensation due to clinical progression without new metastatic lesions. Fatigue was reported in more than 25% of patients (all grades) with only two patients experiencing grade 3 toxicity. Other grade 3 adverse events included dehydration, thrombocytopenia, and weakness.

This study was unable to determine if saracatinib had potential as metastasis inhibitor. Metastasis inhibition by saracatinib may still be viable in an earlier time in the disease history. Prostate © 2015 Wiley Periodicals, Inc.

The Prostate. 2015 Oct 23 [Epub ahead of print]

Edwin M Posadas, Rafi S Ahmed, Theodore Karrison, Russell Z Szmulewitz, Peter H O'Donnell, James L Wade, James Shen, Murali Gururajan, Margarit Sievert, Walter M Stadler

Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California. , Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California. , Biostatistics, Department of Health Service, University of Chicago, Chicago, Illinois. , Genitourinary Oncology Program, Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, Illinois. , Genitourinary Oncology Program, Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, Illinois. , Cancer Care Specialists of Central Illinois, S. C, Decatur, Illinois. , Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California. , Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California. , Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California. , Genitourinary Oncology Program, Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, Illinois.

PubMed

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