Phase I Study of Fenretinide Delivered Intravenously in Patients with Relapsed or Refractory Hematologic Malignancies: A California Cancer Consortium Trial.
Clin Cancer Res
; 23(16): 4550-4555, 2017 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-28420721
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.ExperimentalDesign:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenretinida
/
Neoplasias Hematológicas
Limite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
America do norte
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article