Format

Send to

Choose Destination
Clin Cancer Res. 2017 Aug 15;23(16):4550-4555. doi: 10.1158/1078-0432.CCR-17-0234. Epub 2017 Apr 18.

Phase I Study of Fenretinide Delivered Intravenously in Patients with Relapsed or Refractory Hematologic Malignancies: A California Cancer Consortium Trial.

Author information

1
Division of Hematology, Keck School of Medicine, University of Southern California, Los Angeles, California.
2
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
3
Division of Cancer Treatment and Diagnosis, NCI, NIH, Bethesda, Maryland.
4
John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey.
5
Cancer Center and Departments of Cell Biology and Biochemistry and Pharmacy, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas.
6
Cancer Center and Departments of Cell Biology and Biochemistry, Pediatrics, and Medicine, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas.
7
Department of Cancer Biology, City of Hope Comprehensive Cancer Center, Duarte, California.
8
Cancer Center and Departments of Cell Biology and Biochemistry, Pediatrics, and Medicine, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas. barry.maurer@ttuhsc.edu.

Abstract

Purpose: A phase I study was conducted to determine the MTD, dose-limiting toxicities (DLT), and pharmacokinetics of fenretinide delivered as an intravenous emulsion in relapsed/refractory hematologic malignancies.Experimental Design: Fenretinide (80-1,810 mg/m2/day) was administered by continuous infusion on days 1 to 5, in 21-day cycles, using an accelerated titration design.Results: Twenty-nine patients, treated with a median of three prior regimens (range, 1-7), were enrolled and received the test drug. Ninety-seven courses were completed. An MTD was reached at 1,280 mg/m2/day for 5 days. Course 1 DLTs included 6 patients with hypertriglyceridemia, 4 of whom were asymptomatic; 2 patients experienced DLT thrombocytopenia (asymptomatic). Of 11 patients with response-evaluable peripheral T-cell lymphomas, two had complete responses [CR, progression-free survival (PFS) 68+ months; unconfirmed CR, PFS 14+ months], two had unconfirmed partial responses (unconfirmed PR, PFS 5 months; unconfirmed PR, PFS 6 months), and five had stable disease (2-12 cycles). One patient with mature B-cell lymphoma had an unconfirmed PR sustained for two cycles. Steady-state plasma levels were approximately 10 mcg/mL (mid-20s μmol/L) at 640 mg/m2/day, approximately 14 mcg/mL (mid-30s μmol/L) at 905 mg/m2/day, and approximately 22 mcg/mL (mid-50s μmol/L) at 1,280 mg/m2/day.Conclusions: Intravenous fenretinide obtained significantly higher plasma levels than a previous capsule formulation, had acceptable toxicities, and evidenced antitumor activity in peripheral T-cell lymphomas. A recommended phase II dosing is 600 mg/m2 on day 1, followed by 1,200 mg/m2 on days 2 to 5, every 21 days. A registration-enabling phase II study in relapsed/refractory PTCL (ClinicalTrials.gov identifier: NCT02495415) is ongoing. Clin Cancer Res; 23(16); 4550-5. ©2017 AACR.

PMID:
28420721
PMCID:
PMC5559312
DOI:
10.1158/1078-0432.CCR-17-0234
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center