Long-Term Follow-Up of Desmoid Fibromatosis Treated with PF-03084014, an Oral Gamma Secretase Inhibitor
| Autor: | Patrick J. Blatchford, Victor M. Villalobos, Francis Hall, Wells A. Messersmith, Brianna Hoffner, Rossano Cesari, Lia Gore, Kenneth A. Kern, Antonio Jimeno, Jeffrey Schowinsky, Bo Huang, Anthony D. Elias |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Target lesion medicine.medical_specialty Time Factors Tetrahydronaphthalenes Administration Oral Gastroenterology 03 medical and health sciences 0302 clinical medicine Internal medicine Biopsy Medicine Humans Retrospective Studies medicine.diagnostic_test business.industry Fibromatosis Magnetic resonance imaging Retrospective cohort study Valine medicine.disease Prognosis Confidence interval Surgery Discontinuation Fibromatosis Aggressive 030104 developmental biology Oncology Tolerability 030220 oncology & carcinogenesis Amyloid Precursor Protein Secretases business Follow-Up Studies |
| Zdroj: | Annals of surgical oncology. 25(3) |
| ISSN: | 1534-4681 |
| Popis: | Desmoid fibromatosis is a fibroblastic neoplasm driven by aberrations within the WNT pathway, exhibiting mutations in β-catenin or APC. We review the long-term follow-up of patients in a phase I study treated with an oral gamma secretase inhibitor, PF-03084014. PF-03084014 was administered orally at doses ranging from 20 to 330 mg twice daily. Tumor assessments were performed using computed tomography/magnetic resonance imaging (CT/MRI) within 4 weeks of study entry, and every other cycle through cycle 9. After cycle 9, patients were evaluated as clinically indicated. Seven patients with desmoid fibromatosis were treated between December 2009 and December 2016 at the University of Colorado. Five patients (71.4%, 95% confidence interval [CI] 29.0–96.3%) achieved a partial response (PR), with a mean time to achieving response of 11.9 months (95% CI 2.5–21.4 months). All patients who achieved a PR continue to maintain responses between 47.9 and 73+ months. Four patients stopped treatment yet remain free of progression between 11 and 53+ months. One patient had PFS of 42+ months, with a 17% decrease in the target lesion. A biopsy performed at the end of the study showed decreased tumoral cellularity compared with previous biopsies. Effective treatment doses ranged from 80 to 330 mg administered orally twice daily. PF-03084014 was effective in treating desmoid tumors, with an objective response rate of 71.4% (95% CI 29.0–96.3%) in this small cohort of patients. PF-03084014 exhibits promising activity, even at relatively low doses (80 mg twice daily), with high tolerability leading to prolonged disease control even after therapy discontinuation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink