Muramyl tripeptide in chemotherapy improves overall osteosarcoma survival

Study Type: Therapy
OE Level of Evidence: 2
Journal Level of Evidence: N/A
OE EXCLUSIVE
Dr. Paul A. Meyers discusses the addition of muramyl tripeptide to chemotherapy in the treatment of Osteosarcoma.
Synopsis
662 osteosarcoma patients without detectable metastatic disease were either randomized to three drug (cisplatin, doxorubicin, methotrexate) or four drug chemotherapy (cisplatin, doxorubicin, methotrexate, and ifosfamide). A further comparison was conducted on the effects of the addition muramyl tri-peptide (MTP) to both chemotherapy regimens. Four- and six-year Please login to view the rest of this report. Please login to view the rest of this report.
Funding: Non-Industry funded
Sponsor: National Institutes of Health
Conflicts: None disclosed
CONTENT IS LOCKED
Why was this study needed now?
Osteosarcoma (OS) is a malignant tumour of the bone, with 20% of patients having detectable metastatic disease. The established chemotherapy treatment involves doxorubicin, cisplatin, and high-dose methotrexate with leucovorin rescue (HDMTX). However, recent studies have reported ifosfamide may be beneficial following disease relapse. A previous trial also demonstrated that muramyl tri-peptide phosphatidyl-ethanolamine (MTP-PE) may help target the agent to monocytes and macrophages without increasing toxicity or stimulating cytokines. Therefore, further investigation of the addition of ifosfamide and MTP-PE to the 3-drug chemotherapy regimen (cisplatin, doxorubicin, methotrexate) was needed to see each agent's effect on survival rates in patients with osteosarcoma.
What was the principal research question?
How does the 3-drug therapy (cisplatin, doxorubicin, methotrexate) compare to four-drug therapy (cisplatin, doxorubicin, methotrexate, and ifosfamide) in treatment of osteosarcoma, and does the addition of MTP-PE improve event-free survival (EFS) and overall survival of newly diagnosed patients?
Population: 662 patients with resectable osteosarcoma without clinically detectable metastatic disease (361 males and 301 patients females with ages between 1 to 30 years (median age = 13))
Intervention: Chemotherapy A with MTP-PE: Patients were treated with 3-drug chemotherapy of cisplatin, doxorubicin, methotrexate with addition of muramyl tri-peptide (MTP) Chemotherapy B with MTP-PE: Patients were treated with 4-drug chemotherapy of cisplatin, doxorubicin, methotrexate, and ifosfamide, with addition of muramyl tri-peptide (MTP)
Comparison: Chemotherapy A without MTP-PE: Patients were treated with 3-drug chemotherapy of cisplatin, doxorubicin, methotrexate Chemotherapy B without MTP-PE: Patients were treated with 4-drug chemotherapy of cisplatin, doxorubicin, methotrexate, and ifosfamide Further details can be found at Children's Cancer Group (CCG) and the Pediatric Oncology Group Intergroup Study 0133 (CCG-7921, POG-9351)
Outcomes: Event Free Survival (EFS): the time from study entry until adverse event or last patient contact. Overall survival: the time from entry until death or last patient contact. Adverse events were disease progression, diagnosis of second malignant neoplasm, or death before disease progression.
Methods: RCT: 2x2 factorial design
Time: Median duration of follow-up for patients without adverse events was 7.7 years
What were the important findings?
What should I remember most?
How will this affect the care of my patients?
The authors responsible for this critical appraisal and ACE Report indicate no potential conflicts of interest relating to the content in the original publication.