학술논문
A phase II study of guadecitabine combined with irinotecan vs regorafenib or TAS-102 in irinotecan-refractory metastatic colorectal cancer patients.
Document Type
Academic Journal
Author
Lee V; School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.; Parkinson R; School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.; Zahurak M; School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.; Cope L; School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.; Cercek A; Memorial Sloan Kettering Cancer Center, New York, New York, USA.; Verheul H; Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Gootjes E; Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Lenz HJ; School of Medicine, University of Southern California, Los Angeles, California, USA.; Iqbal S; School of Medicine, University of Southern California, Los Angeles, California, USA.; Jones P; Van Andel Institute, Grand Rapids, Michigan, USA.; Baylin S; School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.; Rami V; School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.; Ahuja N; School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.; El Khoueiry A; School of Medicine, University of Southern California, Los Angeles, California, USA.; Azad NS; School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Source
Publisher: Wiley-Liss Country of Publication: United States NLM ID: 0042124 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-0215 (Electronic) Linking ISSN: 00207136 NLM ISO Abbreviation: Int J Cancer Subsets: MEDLINE
Subject
Language
English
Abstract
DNA methyltransferase inhibitors (DNMTi) have demonstrated benefit in reversing resistance to systemic therapies for several cancer types. In a phase II trial of guadecitabine and irinotecan compared to regorafenib or TAS-102 in pts with advanced mCRC refractory to irinotecan. Patients with mCRC refractory to irinotecan were randomized 2:1 to guadecitabine and irinotecan (Arm A) vs standard of care regorafenib or TAS-102 (Arm B) on a 28-day cycle. Between January 15, 2016 and October 24, 2018, 104 pts were randomized at four international sites, with 96 pts undergoing treatment, 62 in Arm A and 34 in Arm B. Median overall survival was 7.15 months for Arm A and 7.66 months for Arm B (HR 0.93, 95% CI: 0.58-1.47, P = .75). The Kaplan-Meier rates of progression free survival at 4 months were 32% in Arm A and 26% in Arm B. Common ≥Grade 3 treatment related adverse events in Arm A were neutropenia (42%), anemia (18%), diarrhea (11%), compared to Arm B pts with neutropenia (12%), anemia (12%). Guadecitabine and irinotecan had similar OS compared to standard of care TAS-102 or regorafenib, with evidence of target modulation. Clinical trial information: NCT01896856.
(© 2024 UICC.)
(© 2024 UICC.)