Combination of cytotoxic-differentiation therapy with 5-fluorouracil and phenylbutyrate in patients with advanced colorectal cancer
- PMID: 17465233
Combination of cytotoxic-differentiation therapy with 5-fluorouracil and phenylbutyrate in patients with advanced colorectal cancer
Abstract
Background: Phenylbutyrate (PB), a histone deacetylase inhibitor (HDACi), has been shown in laboratory studies to potentiate growth inhibition by 5-fluorouracil (FUra) of human colon carcinoma cells.
Patients and methods: Phase I trial of FUra (24-hour continuous intravenous infusion (CIV)) with dose escalation (2 g/m2 to 2.3 g/m2), in combination with PB (120 hour CIV at fixed dose 410 mg/kg/d x 5), repeated weekly, in patients with advanced colorectal cancer.
Results: Nine patients with metastatic colorectal cancer were treated, 8 of whom were evaluable for toxicity. Toxicities were dose-dependent, reversible and included somnolence, fatigue, confusion, hearing loss, triglyceridemia and hyperuricema. Three out of 4 patients who completed at least 8 weeks of treatment had stable disease (SD) lasting 12+, 25 and 54 weeks (2 out of the 3 patients with SD have had multiple prior chemotherapy regimens).
Conclusion: Weekly infusions of FUra followed by PB were fairly well tolerated with disease stabilization in 3/4 (75%) of patients. This is the first report to demonstrate the feasibility of combining a cytotoxic agent with a HDACi as a cancer treatment.
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