Abstract | PURPOSE: METHODS: Patients received mifamurtide 2 mg/m(2) 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/m(2) 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.
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Authors | P M Anderson, P Meyers, E Kleinerman, K Venkatakrishnan, D P Hughes, C Herzog, W Huh, R Sutphin, Y M Vyas, V Shen, A Warwick, N Yeager, C Oliva, B Wang, Y Liu, A Chou |
Journal | Pediatric blood & cancer
(Pediatr Blood Cancer)
Vol. 61
Issue 2
Pg. 238-44
(Feb 2014)
ISSN: 1545-5017 [Electronic] United States |
PMID | 23997016
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2013 Wiley Periodicals, Inc. |
Chemical References |
- Immunologic Factors
- Phosphatidylethanolamines
- mifamurtide
- Acetylmuramyl-Alanyl-Isoglutamine
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Topics |
- Acetylmuramyl-Alanyl-Isoglutamine
(administration & dosage, analogs & derivatives, pharmacokinetics, pharmacology)
- Adolescent
- Adult
- Bone Neoplasms
(drug therapy, mortality, pathology)
- Child
- Child, Preschool
- Drug-Related Side Effects and Adverse Reactions
- Female
- Follow-Up Studies
- Humans
- Immunologic Factors
(administration & dosage, pharmacokinetics, pharmacology)
- Male
- Middle Aged
- Neoplasm Grading
- Neoplasm Metastasis
- Neoplasm Recurrence, Local
(drug therapy, mortality, pathology)
- Osteosarcoma
(drug therapy, mortality, pathology)
- Phosphatidylethanolamines
(administration & dosage, pharmacokinetics, pharmacology)
- Prognosis
- Safety
- Survival Rate
- Tissue Distribution
- Young Adult
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