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Mifamurtide in metastatic and recurrent osteosarcoma: A patient access study with pharmacokinetic, pharmacodynamic, and safety assessments
Author(s) -
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.
Publication year - 2014
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.24686
Subject(s) - medicine , chills , adverse effect , pharmacokinetics , cohort , pharmacodynamics , neutropenia , osteosarcoma , chemotherapy , surgery , pathology
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/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; t 1/2 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. Pediatr Blood Cancer 2014;61:238–244. © 2013 The Authors. Pediatric Blood & Cancer , published by Wiley Periodicals, Inc.