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

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


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 ( identifier: NCT02495415) is ongoing. Clin Cancer Res; 23(16); 4550-5. ©2017 AACR.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • California
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Resistance, Neoplasm
  • Female
  • Fenretinide / administration & dosage
  • Fenretinide / pharmacokinetics
  • Fenretinide / therapeutic use*
  • Hematologic Neoplasms / drug therapy*
  • Hematologic Neoplasms / pathology
  • Humans
  • Infusions, Intravenous
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Remission Induction
  • Thrombocytopenia / chemically induced
  • Young Adult


  • Antineoplastic Agents
  • Fenretinide

Associated data