Abstract | BACKGROUND: A phase I study was conducted to determine the maximum-tolerated dose, dose-limiting toxicities (DLTs), and pharmacokinetics of fenretinide (4-HPR) delivered in an oral powderized lipid complex (LXS) in patients with relapsed/refractory neuroblastoma. PROCEDURE: 4-HPR/LXS powder (352-2,210 mg/m(2) /day) was administered on Days 0-6, in 21-day courses, by standard 3 + 3 design. RESULTS: Thirty-two patients (median age = 8 years, range 3-27 years) enrolled with 30 evaluable for dose escalation. Prior therapies included stem cell transplantation/support (n = 26), 13-cis-retinoic acid (n = 22), (125/131) I- MIBG (n = 13), and anti-GD2 antibody (n = 6). 170+ courses were delivered. Course 1 DLTs were a Grade 3 (n = 1) alkaline phosphatase at 352 mg/m(2) /day. Other major toxicities were Grade 4 (n = 1) alkaline phosphatases on Courses 5 and 6 at 774 mg/m(2) /day, and Grade 3 (n = 1) ALT/AST elevation on Course 2 at 1,700 mg/m(2) /day. Of 29 response-evaluable patients, six had stable disease (SD) (4-26 courses); four with marrow- or bone disease-only had complete responses (CR) (10-46 courses). 4-HPR plasma levels were several folds higher (P < 0.05) than previously reported using capsular fenretinide. The Day 6 mean peak 4-HPR plasma level at 1,700 mg/m(2) /day was 21 µM. An MTD was not reached. CONCLUSIONS: 4-HPR/LXS oral powder obtained higher plasma levels, with minimal toxicity and evidence of anti- tumor activity, than a previous capsule formulation. A recommended phase II schedule of 4-HPR/LXS powder is 1,500 mg/m(2) /day, TID, on Days 0-6, of a 21-day course.
|
Authors | Barry J Maurer, Min H Kang, Judith G Villablanca, Jitka Janeba, Susan Groshen, Katherine K Matthay, Paul M Sondel, John M Maris, Hollie A Jackson, Fariba Goodarzian, Hiroyuki Shimada, Scarlett Czarnecki, Beth Hasenauer, C Patrick Reynolds, Araz Marachelian |
Journal | Pediatric blood & cancer
(Pediatr Blood Cancer)
Vol. 60
Issue 11
Pg. 1801-8
(Nov 2013)
ISSN: 1545-5017 [Electronic] United States |
PMID | 23813912
(Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2013 Wiley Periodicals, Inc. |
Chemical References |
- Antineoplastic Agents
- Fenretinide
|
Topics |
- Adolescent
- Adult
- Antineoplastic Agents
(administration & dosage, adverse effects, pharmacokinetics)
- Child
- Child, Preschool
- Female
- Fenretinide
(administration & dosage, adverse effects, pharmacokinetics)
- Humans
- Male
- Maximum Tolerated Dose
- Neoplasm Recurrence, Local
(drug therapy)
- Neuroblastoma
(drug therapy)
- Young Adult
|