A phase II study of guadecitabine combined with irinotecan vs regorafenib or TAS-102 in irinotecan-refractory metastatic colorectal cancer patients.
Int J Cancer
; 154(10): 1794-1801, 2024 May 15.
Article
in En
| MEDLINE
| ID: mdl-38312102
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 21 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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Phenylurea Compounds
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Pyridines
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Pyrrolidines
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Rectal Neoplasms
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Azacitidine
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Thymine
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Colorectal Neoplasms
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Trifluridine
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Colonic Neoplasms
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Anemia
Type of study:
Clinical_trials
Limits:
Humans
Language:
En
Journal:
Int J Cancer
Year:
2024
Type:
Article
Affiliation country:
United States