Date of Award

2013

Degree Type

Selective Evidence-Based Medicine Review

Degree Name

Master of Science in Health Sciences - Physician Assistant

Department Chair

John Cavenagh, PhD, PA-C

Abstract

OBJECTIVE: The objective of this selective EBM review is to determine whether or not “Does the addition of muramyl tripeptide to chemotherapy improve overall survival for patients with osteosarcoma?”

STUDY DESIGN: Review of three English language primary randomized controlled trials published between 2005 and 2009.

DATA SOURCES: Randomized controlled trials evaluating the addition of muramyl tripeptide (MTP) to chemotherapy for patients with osteosarcoma were found using Medline/PubMed databases.

OUTCOMES MEASURED: Event-free survival (EFS) and overall survival were the outcome measures used to determine the effectiveness of the additional chemotherapy treatment in osteosarcoma patients. EFS was defined as the time from entry until an adverse event or last patient contact. Overall survival was defined as the time from entry until death or last patient contact.

RESULTS: Three randomized controlled trials were included in this review. A study by Meyers et al could not be analyzed according to its original factorial design due to an interaction between the study interventions. However, a follow up by Meyers et al, reported no evidence of statistically significant interaction between study interventions. The results demonstrated that the addition of MTP to chemotherapy resulted in a trend toward better EFS (p=.08), and improved 6-
year overall survival from 70% to 78% (p=.03). Another study, by Chou et al, looked at the metastatic cohort from Intergroup Study 0133 in isolation, and found that the 5-year EFS for patients who received liposomal MTP was 42% versus 26% for those who did not (RR 0.72; p=.23; 95% CI). The 5-year OS for patients who received MTP versus no MTP was 53% and 40% respectively (RR 0.72; p=0.27; 95% CI).

CONCLUSION: Based on these three trials, it is inconclusive if the addition of MTP to chemotherapy improves overall survival in patients with osteosarcoma. The addition of MTP to chemotherapy has demonstrated a statistically significant improvement in overall survival, as well as a trend toward better EFS, but only in non-metastatic cohorts. The addition of MTP to chemotherapy did not achieve a statistically significant improvement in EFS or overall survival for those with metastatic osteosarcoma. Although the pattern of outcome was similar in all three studies, further research should be aimed at determining a particular chemotherapy plus MTP regimen and a specific patient population for which MTP is most effective.

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