Phase I trial of intravenous fenretinide (4-HPR) plus safingol in advanced malignancies.
Cancer chemotherapy and pharmacology
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).
Boulter, Alexis C; Maurer, Barry J; Pogue, Meredith; Kang, Min H; Cho, Hwangeui; Knight, Amanda; Reynolds, C Patrick; Quick, Donald; Awasthi, Sanjay; and Gerber, David E, "Phase I trial of intravenous fenretinide (4-HPR) plus safingol in advanced malignancies." (2023). Articles, Abstracts, and Reports. 7317.