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.
Prostate
; 76(3): 286-93, 2016 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-26493492
ABSTRACT
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Quinazolinas
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Centros Médicos Acadêmicos
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Benzodioxóis
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Neoplasias de Próstata Resistentes à Castração
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Metástase Neoplásica
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Antineoplásicos
Tipo de estudo:
Clinical_trials
Limite:
Aged
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Aged80
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Humans
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Male
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Middle aged
País como assunto:
America do norte
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article