Positive Health Online

Abstract

MAURER and COLLEAGUES,  (1)Department of Cell Biology & Biochemistry, Texas Tech University Health Sciences  Center, Lubbock, Texas; Department of Pediatrics, Texas Tech University Health Sciences Center, Lubbock, Texas; Department of Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas conducted a phase I study of fenretinide in an oral powderized lipid complex in patients with relapsed/refractory neuroblastoma.

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.

Methodology

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.

Conclusion

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.

References

Maurer BJ(1), Kang MH, Villablanca JG, Janeba J, Groshen S, Matthay KK, Sondel PM, Maris JM, Jackson HA, Goodarzian F, Shimada H, Czarnecki S, Hasenauer B, Reynolds CP, Marachelian A. Phase I trial of fenretinide delivered orally in a novel organized lipid complex  in patients with relapsed/refractory neuroblastoma: a report from the New Approaches to Neuroblastoma Therapy (NANT) consortium. Pediatr Blood Cancer: 60(11):1801-8. Nov 2013. doi: 10.1002/pbc.24643. Epub Jun 29 2013.