H Hirte1, S Lheureux2, G F Fleming3, A Sugimoto4, R Morgan5, J Biagi6, L Wang2, S McGill2, S P Ivy7, A M Oza8. 1. Juravinski Cancer Centre, Hamilton, ON, Canada. 2. Princess Margaret Cancer Centre, Toronto, ON, Canada. 3. The University of Chicago Medical Center, Chicago, IL, United States. 4. London Health Sciences Centre, London, ON, Canada. 5. City of Hope Medical Center, Duarte, CA, United States. 6. Cancer Centre of Southeastern Ontario, Kingston, ON, Canada. 7. National Cancer Institute, Bethesda, MD, United States. 8. Princess Margaret Cancer Centre, Toronto, ON, Canada. Electronic address: amit.oza@uhn.ca.
Abstract
PURPOSE: Cediranib is a potent multitargeted inhibitor of vascular endothelial growth factor receptor (VEGFR) 1, 2 and 3. The study was initiated to evaluate the activity of cediranib in patients (pts) with recurrent ovarian, peritoneal or fallopian tube cancer (OC). METHODS: Eligible pts had persistent/recurrent OC following one prior platinum-based chemotherapy with measurable disease or progression based on Gynecologic Cancer Inter Group CA-125 criteria. Because of toxicities observed in the first 23 pts, the initial starting dose of oral daily (od) cediranib was reduced from 45mg to 30mg. The primary endpoint was objective response rate at 16weeks. This study was stratified into two arms: platinum-sensitive (PL-S) and platinum-resistant (PL-R). RESULTS: 74 pts were enrolled; 39 were PL-S and 35 PL-R, with a median age of 58years [31-87]. In PL-S group, 10 (26%) partial responses (PR) and 20 (51%) stable disease (SD) were confirmed while in the PL-R arm there were no confirmed PR and 23 pts (66%) had SD. The main grade 3/4 toxicities observed at the 30 mg starting dose were hypertension (27%), fatigue (20%) and diarrhea (14%). The median progression-free survival for all patients was 4.9months [3.9-7.0], 7.2months [4.3-9] for PL-S and 3.7months [2.6-4.5] for PL-R groups. The median overall survival was 18.9months (95% CI: 13.5-31.5); 27.7months [17.8-43.3] for PL-S and 11.9months [8.1-18.9] for PL-R groups. CONCLUSION: Cediranib shows significant activity in recurrent platinum sensitive OC. The toxicities were expected and manageable at the dose of 30mg od.
PURPOSE:Cediranib is a potent multitargeted inhibitor of vascular endothelial growth factor receptor (VEGFR) 1, 2 and 3. The study was initiated to evaluate the activity of cediranib in patients (pts) with recurrent ovarian, peritoneal or fallopian tube cancer (OC). METHODS: Eligible pts had persistent/recurrent OC following one prior platinum-based chemotherapy with measurable disease or progression based on Gynecologic Cancer Inter Group CA-125 criteria. Because of toxicities observed in the first 23 pts, the initial starting dose of oral daily (od) cediranib was reduced from 45mg to 30mg. The primary endpoint was objective response rate at 16weeks. This study was stratified into two arms: platinum-sensitive (PL-S) and platinum-resistant (PL-R). RESULTS: 74 pts were enrolled; 39 were PL-S and 35 PL-R, with a median age of 58years [31-87]. In PL-S group, 10 (26%) partial responses (PR) and 20 (51%) stable disease (SD) were confirmed while in the PL-R arm there were no confirmed PR and 23 pts (66%) had SD. The main grade 3/4 toxicities observed at the 30 mg starting dose were hypertension (27%), fatigue (20%) and diarrhea (14%). The median progression-free survival for all patients was 4.9months [3.9-7.0], 7.2months [4.3-9] for PL-S and 3.7months [2.6-4.5] for PL-R groups. The median overall survival was 18.9months (95% CI: 13.5-31.5); 27.7months [17.8-43.3] for PL-S and 11.9months [8.1-18.9] for PL-R groups. CONCLUSION:Cediranib shows significant activity in recurrent platinum sensitive OC. The toxicities were expected and manageable at the dose of 30mg od.
Authors: Ilary Ruscito; Maria Luisa Gasparri; Claudia Marchetti; Caterina De Medici; Carlotta Bracchi; Innocenza Palaia; Sara Imboden; Michael D Mueller; Andrea Papadia; Ludovico Muzii; Pierluigi Benedetti Panici Journal: Tumour Biol Date: 2016-01-11
Authors: Joleen M Hubbard; Jun Yin; Erin L Schenk; Rui Qin; Joel M Reid; Carrie Strand; Jack Fiskum; Michael Menefee; Grace Lin; L Austin Doyle; Percy Ivy; Charles Erlichman; Alex Adjei; Paul Haluska; Brian A Costello Journal: Invest New Drugs Date: 2021-09-13 Impact factor: 3.850