A phase II study of guadecitabine combined with irinotecan vs regorafenib or TAS-102 in irinotecan-refractory metastatic colorectal cancer patients Journal Article
| Authors: | Lee, V.; Parkinson, R.; Zahurak, M.; Cope, L.; Cercek, A.; Verheul, H.; Gootjes, E.; Lenz, H. J.; Iqbal, S.; Jones, P.; Baylin, S.; Rami, V.; Ahuja, N.; El Khoueiry, A.; Azad, N. S. |
| Article Title: | A phase II study of guadecitabine combined with irinotecan vs regorafenib or TAS-102 in irinotecan-refractory metastatic colorectal cancer patients |
| 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. |
| Keywords: | adult; controlled study; treatment outcome; aged; survival rate; major clinical study; overall survival; clinical feature; clinical trial; neutropenia; cancer combination chemotherapy; dose response; drug efficacy; pyridines; antineoplastic agent; progression free survival; phase 2 clinical trial; anemia; randomized controlled trial; antineoplastic combined chemotherapy protocols; colonic neoplasms; drug effect; pathology; risk factor; irinotecan; colorectal neoplasms; drug combination; colorectal tumor; colon tumor; open study; clinical effectiveness; drug combinations; rectal neoplasms; rectum tumor; phase ii; azacitidine; pyridine derivative; pyrrolidines; thymine; metastatic colorectal cancer; comparative effectiveness; epigenetic therapy; metastatic colon cancer; regorafenib; phenylurea compounds; carbanilamide derivative; humans; human; male; female; article; pyrrolidine derivative; guadecitabine; tipiracil plus trifluridine; trifluridine; trifluridine tipiracil drug combination |
| Journal Title: | International Journal of Cancer |
| Volume: | 154 |
| Issue: | 10 |
| ISSN: | 0020-7136 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2024-05-15 |
| Start Page: | 1794 |
| End Page: | 1801 |
| Language: | English |
| DOI: | 10.1002/ijc.34845 |
| PUBMED: | 38312102 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
