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.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.|Division of Hematology/Oncology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
Edwin M
EM
Posadas
Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.|Division of Hematology/Oncology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
Rafi S
RS
Ahmed
Biostatistics, Department of Health Service, University of Chicago, Chicago, Illinois.
Theodore
T
Karrison
Genitourinary Oncology Program, Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, Illinois.
Russell Z
RZ
Szmulewitz
Genitourinary Oncology Program, Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, Illinois.
Peter H
PH
O'Donnell
Cancer Care Specialists of Central Illinois, S.C, Decatur, Illinois.
James L
JL
Wade
Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.|Division of Hematology/Oncology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
James
J
Shen
Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Murali
M
Gururajan
Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Margarit
M
Sievert
Genitourinary Oncology Program, Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, Illinois.
Walter M
WM
Stadler
D000046:Academic Medical Centers; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D052117:Benzodioxoles / Q000627:therapeutic use*; D002641:Chicago; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000175:diagnosis* / Q000188:drug therapy*; D011799:Quinazolines / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D052117:Benzodioxoles; D011799:Quinazolines; C515233:saracatinib
Fyn; azd0530; castration-resistant; prostate cancer; saracatinib