| Autor: |
Jan Scicinski, George Fisher, Corey Carter, Cheryl Cho-Phan, Pamela Kunz, Shoucheng Ning, Susan Knox, Bryan Oronsky, Scott Caroen, Christopher Parker, Gary Fanger, Tony Reid |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Předmět: |
|
| Zdroj: |
Redox Biology, Vol 5, Iss , Pp 422- (2015) |
| Druh dokumentu: |
article |
| ISSN: |
2213-2317 |
| DOI: |
10.1016/j.redox.2015.09.035 |
| Popis: |
Background: RRx-001 is a novel NO and hypoxia mediated anticancer agent with epigenetic activity. In the first-in-human, Phase I trial, 5/5 patients who progressed on RRx-001 treatment were resensitized to previously refractory therapy, hinting at a generalized resensitization effect. Aims: A randomized open-label multi-part, multi-center phase II trial of RRx-001 versus regorafenib (ROCKET) has commenced to explore the resensitization and/or ‘episensitization’ potential in irinotecan refractory tumors and its impact on overall survival. Methods: Patients with irinotecan-refractory metastatic colorectal cancer with an ECOG PS 0–1 who progressed on oxaliplatin-, and irinotecan-based regimens with or without bevacizumab, cetuximab or panitumumab are randomized 2:1 to receive RRx-001 16.5mg/m2 IV 1x/week or regorafenib 160mg orally 21 of 28 days until progression or unacceptable toxicity followed by treatment with refractory irinotecan-based therapies. Results: To date, 26 patients have been randomized with 18 patients evaluable for resensitization. Post RRx-001 patients demonstrated marked decreases in CEA in 12/13 patients as compared to 5 patients receiving regorafenib who were too systemically unwell to proceed to subsequent treatment. Progression free survival (ongoing) for RRx-001+irinotecan is 4.9 months compared 1.8 months on Regorafenib+irinotecan. Conclusion: Early results in the ROCKET study suggest that RRx-001-mediated resensitization to previously refractory therapies may have a generalized effect, independent of KRAS or p53 status. These early results are intriguing, suggesting improved QOL and overall survival over currently approved therapy in the chemotherapy refractory colorectal cancer. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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