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An open‐label, phase 2 trial of RPI.4610 (angiozyme) in the treatment of metastatic breast cancer
Author(s) -
Morrow Phuong Khanh,
Murthy Rashmi K.,
Ensor Joe D.,
Gordon Gilad S.,
Margolin Kim A.,
Elias Anthony D.,
Urba Walter J.,
Weng David E.,
Rugo Hope S.,
Hortobagyi Gabriel N.
Publication year - 2012
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.26730
Subject(s) - medicine , nausea , gastroenterology , phases of clinical research , chemotherapy , adverse effect , vomiting , metastatic breast cancer , progressive disease , breast cancer , cancer , oncology , surgery
BACKGROUND: Serum and plasma levels of vascular endothelial growth factor (VEGF) correlate with prognosis in patients with metastatic breast cancer (MBC). VEGF binds to 2 receptors on endothelial cells, VEGFR‐1 and VEGFR‐2. RPI.4610 (Angiozyme0) is an antiangiogenic ribozyme targeting the VEGFR‐1 mRNA. Preclinical and phase 1 studies suggested that RPI.4610 is a well‐tolerated agent with clinical activity in solid tumors. The authors' trial evaluated the efficacy of RPI.4610 in the treatment of patients with progressive MBC. METHODS: This phase 2, multicenter, single‐arm study was designed to assess the objective response rate of RPI.4610 in patients with MBC who had experienced disease progression with at least 1 course of chemotherapy for MBC. Patients received daily subcutaneous injections of RPI.4610 100 mg/m 2 for 12 weeks. RESULTS: Most patients (93%) had received at least 2 lines of chemotherapy previously; 69% of patients had received at least 3 lines of chemotherapy. Median follow‐up was 2.76 months (range, 0.89‐36.6 months). No partial responses nor complete responses were found. Median progression‐free survival was 1.41 months (95% confidence interval [CI], 1.35‐1.45). The median overall survival from start of treatment was 11.89 months (95% CI, 4.11‐23.66). Treatment‐related adverse events (AEs) were primarily grade 1 to 2 in intensity. Most common AEs were: injection site reactions, abdominal pain, anorexia, chromaturia, constipation, dyspnea, fatigue, headache, pain at the injection site, nausea, vomiting, and fever. CONCLUSIONS: Although RPI.4610 demonstrated a well‐tolerated safety profile, its lack of clinical efficacy precludes this drug from further development. Cancer 2012.© 2012 American Cancer Society.