Journal article
Mifamurtide in metastatic and recurrent osteosarcoma: A patient access study with pharmacokinetic, pharmacodynamic, and safety assessments
Pediatric blood & cancer, Vol.61(2), pp.238-244
02/2014
DOI: 10.1002/pbc.24686
PMCID: PMC4533988
PMID: 23997016
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 2 mg/m2 intravenously twice‐weekly ×12 weeks, then weekly ×24 weeks with and without chemotherapy. Serum concentration‐time profiles were collected. Adverse events within 24 hours 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 30 minutes post‐infusion, then in a log‐linear manner 2–6 hours post‐dose; t1/2 was 2 hours. There were no readily apparent relationships between age and BSA‐normalized clearance, half‐life, or pharmacodynamic effects, supporting the dose of 2 mg/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. Pediatr Blood Cancer 2014;61:238–244. © 2013 The Authors. Pediatric Blood & Cancer, published by Wiley Periodicals, Inc.
Details
- Title: Subtitle
- Mifamurtide in metastatic and recurrent osteosarcoma: A patient access study with pharmacokinetic, pharmacodynamic, and safety assessments
- Creators
- P.M Anderson - University of Texas M.D. Anderson Cancer CenterY.M Vyas - University of IowaP Meyers - Memorial Sloan‐Kettering Cancer CenterN Yeager - Ohio State UniversityC Oliva - MD AndersonB Wang - Millennium: The Takeda Oncology CompanyE Kleinerman - University of Texas M.D. Anderson Cancer CenterK Venkatakrishnan - MD AndersonD.P Hughes - University of Texas M.D. Anderson Cancer CenterC Herzog - University of Texas M.D. Anderson Cancer CenterW Huh - University of Texas M.D. Anderson Cancer CenterR Sutphin - MD AndersonV Shen - Childrens Hospital of Orange CountyA Warwick - Uniformed Services UniversityY Liu - Millennium: The Takeda Oncology CompanyA Chou - Memorial Sloan‐Kettering Cancer Center
- Resource Type
- Journal article
- Publication Details
- Pediatric blood & cancer, Vol.61(2), pp.238-244
- DOI
- 10.1002/pbc.24686
- PMID
- 23997016
- PMCID
- PMC4533988
- NLM abbreviation
- Pediatr Blood Cancer
- ISSN
- 1545-5009
- eISSN
- 1545-5017
- Number of pages
- 7
- Grant note
- Haynie Spirit Fund Wilkes Family Sarah's Garden of Hope Curtis family (Distinguished Professor Endowment for Pediatric Cancer Research) Lauren Behr (Sarcoma Research Fund)
- Language
- English
- Date published
- 02/2014
- Academic Unit
- Stead Family Department of Pediatrics
- Record Identifier
- 9984093371602771
Metrics
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