Title

Phase I trial of intravenous fenretinide (4-HPR) plus safingol in advanced malignancies.

Document Type

Article

Publication Date

5-18-2023

Publication Title

Cancer chemotherapy and pharmacology

Keywords

texas; covenant

Abstract

PURPOSE: Fenretinide (4-HPR) is a synthetic retinoid that induces cytotoxicity through dihydroceramide production. Safingol, a stereochemical-variant dihydroceramide precursor, exhibits synergistic effects when administered with fenretinide in preclinical studies. We conducted a phase 1 dose-escalation clinical trial of this combination.

METHODS: Fenretinide was administered as a 600 mg/m

RESULTS: A total of 16 patients were enrolled (mean age 63 years, 50% female, median three prior lines of therapy), including 15 patients with refractory solid tumors and one with non-Hodgkin lymphoma. The median number of treatment cycles received was 2 (range 2-6). The most common adverse event (AE) was hypertriglyceridemia (88%; 38% ≥ Grade 3), attributed to the fenretinide intralipid infusion vehicle. Other treatment-related AEs occurring in ≥ 20% of patients included anemia, hypocalcemia, hypoalbuminemia, and hyponatremia. At safingol dose 420 mg/m

CONCLUSION: Combination fenretinide plus safingol commonly causes hypertriglyceridemia and may be associated with cardiac events at higher safingol levels. Minimal activity in refractory solid tumors was observed.

TRIAL REGISTRATION NUMBER: NCT01553071 (3.13.2012).

Clinical Institute

Cancer

Department

Oncology

Department

Pharmacy

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