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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 4/2021

01-04-2021 | Solid Tumor | Original Article

A phase I study of intravenous fenretinide (4-HPR) for patients with malignant solid tumors

Authors: Jacob S. Thomas, Anthony B. El-Khoueiry, Barry J. Maurer, Susan Groshen, Jacek K. Pinski, Everardo Cobos, David R. Gandara, Heinz J. Lenz, Min H. Kang, C. Patrick Reynolds, Edward M. Newman

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2021

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Abstract

Background

Fenretinide is a synthetic retinoid that can induce cytotoxicity by several mechanisms. Achieving effective systemic exposure with oral formulations has been challenging. An intravenous lipid emulsion fenretinide formulation was developed to overcome this barrier. We conducted a study to establish the maximum tolerated dose (MTD), preliminary efficacy, and pharmacokinetics of intravenous lipid emulsion fenretinide in patients with advanced solid tumors.

Methods

Twenty-three patients with advanced solid tumors refractory to standard treatments received fenretinide as a continuous infusion for five consecutive days in 21-day cycles. Five different dose cohorts were evaluated between doses of 905 mg/m2 and 1414 mg/m2 per day using a 3 + 3 dose escalation design. A priming dose of 600 mg/m2 on day 1 was introduced in an attempt to address the asymptomatic serum triglyceride elevations related to the lipid emulsion.

Results

The treatment-related adverse events occurring in ≥ 20% of patients were anemia, hypertriglyceridemia, fatigue, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) increase, thrombocytopenia, bilirubin increase, and dry skin. Five evaluable patients had stable disease as best response, and no patients had objective responses. Plasma steady-state concentrations of the active metabolite were significantly higher than with previous capsule formulations.

Conclusion

Fenretinide emulsion intravenous infusion had a manageable safety profile and achieved higher plasma steady-state concentrations of the active metabolite compared to previous capsule formulations. Single-agent activity was minimal but combinatorial approaches are under evaluation.
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Metadata
Title
A phase I study of intravenous fenretinide (4-HPR) for patients with malignant solid tumors
Authors
Jacob S. Thomas
Anthony B. El-Khoueiry
Barry J. Maurer
Susan Groshen
Jacek K. Pinski
Everardo Cobos
David R. Gandara
Heinz J. Lenz
Min H. Kang
C. Patrick Reynolds
Edward M. Newman
Publication date
01-04-2021
Publisher
Springer Berlin Heidelberg
Keyword
Solid Tumor
Published in
Cancer Chemotherapy and Pharmacology / Issue 4/2021
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-020-04224-8

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