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Selinexor (KPT-330), an oral Selective Inhibitor of Nuclear Export (SINE) compound, in combination with FOLFOX in patients with metastatic colorectal cancer (mCRC) : final results of the phase I Trial SENTINEL
- Source :
- Current cancer drug targets
- Publication Year :
- 2020
-
Abstract
- Background: Selinexor is an oral Selective Inhibitor of Nuclear Export compound that specifically blocks Chromosomal Region Maintenance protein 1. Objective: To evaluate the safety and tolerability of escalating doses of selinexor plus 5-fluorouracil, leucovorin and oxaliplatin (mFOLFOX6) in metastatic colorectal cancer (mCRC) patients. Methods: In this multicenter phase I trial, mCRC patients, eligible for oxaliplatin-based treatment, were enrolled to receive oral selinexor on days 1, 3, and 8 plus mFOLFOX6 every two weeks. Primary endpoint was the maximum tolerated dose. Secondary endpoints were toxicity, overall response rate, progression free survival, and overall survival. Results: Overall, 10 patients were enrolled, who had prior treatment with oxaliplatin (6/10), irinotecan (8/10), bevacizumab (6/10) or anti-EGFR therapy (5/10). Four consecutive patients received 40 mg selinexor plus mFOLFOX6. All four experienced dose-limiting toxicities and withdrew from the study after a median of two cycles. Thus, this dose level was regarded as toxic and no further patients were evaluated at this dose. Six patients were enrolled with 20 mg selinexor plus mFOLFOX6. Despite better tolerability, four patients withdrew (patient wish) after the first cycle and only two patients continued until disease progression. Most commonly reported treatment emergent adverse events were nausea (80%), diarrhea (70%), vomiting (60%), fatigue (60%), anorexia (40%), and impaired vision (40%). Due to the short treatment exposure, no relevant clinical activity was observed. Conclusion: In patients with metastatic colorectal cancer, selinexor on this dose schedule plus mFOLFOX6 was not tolerable. Other dosing schedules or combinations may be evaluated. Clinical trial identifier NCT02384850.
- Subjects :
- 0301 basic medicine
Oncology
Male
Cancer Research
medicine.medical_specialty
Bevacizumab
Maximum Tolerated Dose
Active Transport, Cell Nucleus
Leucovorin
Phases of clinical research
03 medical and health sciences
0302 clinical medicine
FOLFOX
Internal medicine
Drug Discovery
Antineoplastic Combined Chemotherapy Protocols
Medicine
Humans
Progression-free survival
Neoplasm Metastasis
Aged
Pharmacology
business.industry
Middle Aged
Triazoles
Prognosis
Oxaliplatin
Irinotecan
Survival Rate
030104 developmental biology
Hydrazines
Tolerability
030220 oncology & carcinogenesis
Chromosomal region
Female
Fluorouracil
Human medicine
business
Colorectal Neoplasms
medicine.drug
Follow-Up Studies
Subjects
Details
- Language :
- English
- ISSN :
- 15680096
- Database :
- OpenAIRE
- Journal :
- Current cancer drug targets
- Accession number :
- edsair.doi.dedup.....b2cdeae5acb8e7f3029853bf8c22497a