Evaluating the Outcome and Patient Safety of Methotrexate, Doxorubicin, and Cisplatin Regimen for Chemotherapy in Osteosarcoma: A Meta-Analysis

Document Type : Systematic Review and Meta-analysis


1 Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.

2 Department of Orthopaedic and Traumatology, Faculty of Medicine, Udayana University, Denpasar, Indonesia.

3 Faculty of Medicine, Maranatha Christian University, Bandung, Indonesia.


Background: Several studies of multi-drug regimens for osteosarcoma have shown different efficacies and are still controversial. Meanwhile, chemotherapy options have remained largely unchanged over a couple of decades. This study is designed to ascertain the outcome and safety of Methotrexate, Doxorubicin, and Cisplatin regimen for chemotherapy in osteosarcoma patients through the utilization of meta-analysis. Methods: We interrogated trials that compared the MAP regimen with other regimens as chemotherapy for osteosarcoma from several databases encompassing PubMed, Science Direct, and grey literature (Google Scholar) until December 2022. The analyzed outcomes including Event-Free Survival (EFS), Overall Survival (OS), Tumor Necrosis (TN) rate, and Adverse Event (AE) were then analyzed using RevMan 5.4 software in fixed or random effect models. Results: Our meta-analysis comprised 8 prospective articles that evaluated a cumulative number of 2920 OS patients. The analysis results indicated no meaningful difference in 5-year EFS (OR=0.99, 95% CI=0.77–1.27, [P = 0.91]) and neoadjuvant chemotherapy response (TN) (OR=0.76, 95% CI=0.49-1.17, [P = 0.22]) between the MAP and control groups. Furthermore, 5-year OS analysis revealed a significant association in the control group (OR=0.82, 95% CI=0.68-0.99, [P = 0.04]). However, the control group was associated with statistically meaningful AE compared to the MAP group, particularly in thrombocytopenia (OR=0.46, 95% CI=0.23-0.90, [P = 0.02]) and fever (OR=0.34, 95% CI=0.26-0.46, [P < 0.00001]). Conclusion: The present meta-analysis showed that the MAP regimen remains preferable in treating osteosarcoma patients despite no significant outcome compared to the other regimens considering the less frequent AE in the MAP regimen.


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