Mifamurtide in metastatic and recurrent osteosarcoma: A patient access study with pharmacokinetic, pharmacodynamic, and safety assessments Journal Article
| Authors: | Anderson, P. M.; Meyers, P.; Kleinerman, E.; Venkatakrishnan, K.; Hughes, D. P.; Herzog, C.; Huh, W.; Sutphin, R.; Vyas, Y. M.; Shen, V.; Warwick, A.; Yeager, N.; Oliva, C.; Wang, B.; Liu, Y.; Chou, A. |
| Article Title: | Mifamurtide in metastatic and recurrent osteosarcoma: A patient access study with pharmacokinetic, pharmacodynamic, and safety assessments |
| Abstract: | Purpose: This non-randomized, patient-access protocol, assessed both safety and efficacy outcomes following liposomal muramyl-tripeptide-phosphatidylethanolamine (L-MTP-PE; mifamurtide) in patients with high-risk, recurrent and/or metastatic osteosarcoma. Methods: Patients received mifamurtide 2mg/m2 intravenously twice-weekly ×12 weeks, then weekly ×24 weeks with and without chemotherapy. Serum concentration-time profiles were collected. Adverse events within 24hours of drug administration were classified as infusion-related adverse events (IRAE); other AEs and overall survival (OS) were assessed. Results: The study began therapy in January 2008; the last patient completed therapy in October 2012. Two hundred five patients were enrolled; median age was 16.0 years and 146/205 (71%) had active disease. Mifamurtide serum concentrations declined rapidly in the first 30minutes post-infusion, then in a log-linear manner 2-6hours post-dose; t1/2 was 2hours. There were no readily apparent relationships between age and BSA-normalized clearance, half-life, or pharmacodynamic effects, supporting the dose of 2mg/m2 mifamurtide across the age range. Patients reported 3,679 IRAE after 7,482 mifamurtide infusions. These were very rarely grade 3 or 4 and most commonly included chills+fever or headache+fatigue symptom clusters. One- and 2-year OS was 71.7% and 45.9%. Patients with initial metastatic disease or progression approximated by within 9 months of diagnosis (N=40) had similar 2-year OS (39.9%) as the entire cohort (45.9%) Conclusions: Mifamurtide had a manageable safety profile; PK/PD of mifamurtide in this patient access study was consistent with prior studies. Two-year OS was 45.9%. A randomized clinical trial would be required to definitively determine impact on patient outcomes. © 2013 Wiley Periodicals, Inc. |
| Keywords: | osteosarcoma; biologic therapy; pharmacokinetics; mifamurtide; macrophage activation; l-mtp-pe |
| Journal Title: | Pediatric Blood and Cancer |
| Volume: | 61 |
| Issue: | 2 |
| ISSN: | 1545-5009 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2014-02-01 |
| Start Page: | 238 |
| End Page: | 244 |
| Language: | English |
| DOI: | 10.1002/pbc.24686 |
| PROVIDER: | scopus |
| PUBMED: | 23997016 |
| PMCID: | PMC4533988 |
| DOI/URL: | |
| Notes: | Export Date: 3 February 2014 -- CODEN: PBCEA -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work