Ian Judson 1 , Michelle Scurr 2 , Kate Gardner 2 , Elizabeth Barquin 2 , Marcelo Marotti 3 , Barbara Collins 3 , Helen Young 3 , Juliane M Jürgensmeier 3 , Michael Leahy 4 Show Affiliations »
Abstract
PURPOSE: Cediranib is a potent VEGF signaling inhibitor with activity against all three VEGF receptors and KIT. This phase II study evaluated the antitumor activity of cediranib in patients with metastatic gastrointestinal stromal tumor (GIST) resistant/intolerant to imatinib, or metastatic soft-tissue sarcomas (STS; ClinicalTrials.gov, NCT00385203). EXPERIMENTAL DESIGN: Patients received cediranib 45 mg/day. Primary objective was to determine the antitumor activity of cediranib according to changes in 2[18F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)FDG-PET) tumor uptake in patients with GIST using maximum standardized uptake values (SUVmax). Secondary objectives included objective tumor response and tolerability in patients with GIST/STS. RESULTS: Thirty-four of 36 enrolled patients were treated (GIST n = 24; STS n = 10). At day 29, five patients had confirmed decreases in SUVmax (≥10% from day 8) and two had confirmed partial metabolic responses (≥25% decrease), but arithmetic mean percentage changes in SUVmax, averaged across the cohort, were not significant at day 8 [6.8%; 95% confidence interval (CI), 19.95-33.54) or day 29 (4.6%; 95% CI, 8.05-17.34). Eleven patients with GIST achieved a best objective tumor response of stable disease; eight achieved stable disease ≥16 weeks. In patients with STS, four of six with alveolar soft-part sarcoma (ASPS) achieved confirmed and durable partial responses. The commonest adverse events were diarrhea (85%), fatigue (74%), and hypertension (68%). CONCLUSIONS: In patients progressing on imatinib/sunitinib, cediranib 45 mg/day demonstrated evidence of activity by (18)FDG-PET, but did not reduce average SUVmax. Evidence of antitumor activity was seen in ASPS. ©2014 American Association for Cancer Research.
PURPOSE: Cediranib is a potent VEGF signaling inhibitor with activity against all three VEGF receptors and KIT . This phase II study evaluated the antitumor activity of cediranib in patients with metastatic gastrointestinal stromal tumor (GIST) resistant/intolerant to imatinib , or metastatic soft-tissue sarcomas (STS; ClinicalTrials.gov, NCT00385203). EXPERIMENTAL DESIGN: Patients received cediranib 45 mg/day. Primary objective was to determine the antitumor activity of cediranib according to changes in 2[18F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)FDG-PET) tumor uptake in patients with GIST using maximum standardized uptake values (SUVmax). Secondary objectives included objective tumor response and tolerability in patients with GIST/STS. RESULTS: Thirty-four of 36 enrolled patients were treated (GIST n = 24; STS n = 10). At day 29, five patients had confirmed decreases in SUVmax (≥10% from day 8) and two had confirmed partial metabolic responses (≥25% decrease), but arithmetic mean percentage changes in SUVmax, averaged across the cohort, were not significant at day 8 [6.8%; 95% confidence interval (CI), 19.95-33.54) or day 29 (4.6%; 95% CI, 8.05-17.34). Eleven patients with GIST achieved a best objective tumor response of stable disease; eight achieved stable disease ≥16 weeks. In patients with STS, four of six with alveolar soft-part sarcoma (ASPS ) achieved confirmed and durable partial responses. The commonest adverse events were diarrhea (85%), fatigue (74%), and hypertension (68%). CONCLUSIONS: In patients progressing on imatinib /sunitinib , cediranib 45 mg/day demonstrated evidence of activity by (18)FDG-PET, but did not reduce average SUVmax. Evidence of antitumor activity was seen in ASPS . ©2014 American Association for Cancer Research.
Entities: Chemical
Disease
Gene
Species
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Year: 2014
PMID： 24714778 DOI： 10.1158/1078-0432.CCR-13-1881
Source DB: PubMed Journal: Clin Cancer Res ISSN： 1078-0432 Impact factor: 12.531