Efficacy Comparison of Six Chemotherapeutic Combinations for Osteosarcoma and Ewing's Sarcoma Treatment: A Network Meta‐Analysis

Abstract

This study aimed to address the insufficiency of traditional meta-analysis and provide improved guidelines for the clinical practice of osteosarcoma treatment. The heterogeneity of the fixed-effect model was calculated, and when necessary, a random-effect model was adopted. Furthermore, the direct and indirect evidence was pooled together and exhibited in the forest plot and slash table. The surface under the cumulative ranking curve (SUCRA) value was also measured to rank each intervention. Finally, heat plot was introduced to demonstrate the contribution of each intervention and the inconsistency between direct and indirect comparisons. This network meta-analysis included 32 trials, involving a total of 5,626 subjects reported by 28 articles. All the treatments were classified into six chemotherapeutic combinations: dual agent with or without ifosfamide (IFO), multi-agent with or without IFO, and dual agent or multi-agent with IFO and etoposide. For the primary outcomes, both overall survival (OS) and event-free survival (EFS) rates were considered. The multi-agent integrated with IFO and etoposide showed an optimal performance for 5-year OS, 10-year OS, 3-year EFS, 5-year EFS, and 10-year EFS when compared with placebo. The SUCRA value of this treatment was also the highest of these six interventions. However, multi-drug with IFO alone had the highest SUCRA value of 0.652 and 0.516 when it came to relapse and lung-metastasis. It was efficient to some extent, but no significant difference was observed in both outcomes. Chemotherapy, applied as induction or adjuvant treatment with radiation therapy or surgery, is able to increase the survival rate of patients, especially by combining multi-drug with IFO and etoposide, which demonstrated the best performance in both OS and EFS. As for relapse and the lung-metastasis, multiple agents with IFO alone seemed to have the optimal efficiency, although no significant difference was observed here.

Mediating effect assessment of ifosfamide on limb salvage rate in osteosarcoma: A study from a single center in China

“…Ifosfamide has also been responsible for a series of more specific, potentially life-threatening toxicities: hemorrhagic cystitis, nephropathy, encephalopathy, and cardiac toxicity (29-32). Zhang T et al found that the MAPIE regimen may perform well in OS and EFS, and it seemed to have the optimal efficiency in relapse and the lung-metastasis osteosarcoma (33). To sum up, most of the current studies on osteosarcoma focus on how to improve the long-term survival of patients with osteosarcoma, but, up until now, there is little research on the relationship between the neoadjuvant chemotherapy regimen and its influence on the surgical options of limb salvage or amputation.…”

Nano-Based Drug Delivery Systems: Potential Developments in the Therapy of Metastatic Osteosarcoma—A Narrative Review

“…Innovations in chemotherapeutic strategies for metastatic osteosarcoma have come to the fore recently. Specifically, the introduction of ifosfamide and etoposide into treatment regimens has garnered significant attention and optimism within the oncological sphere [ 68 , 69 , 70 , 71 , 72 , 73 ]. These agents have demonstrated promising results, particularly in patients who had limited or unfavorable responses to initial chemotherapy phases.…”

Cellular toxicology and mechanism of the response to silver-based nanoparticle exposure in Ewing’s sarcoma cells

“…However, the benefits of this therapeutic strategy remain controversial because of the conflicting results obtained [10]. In chemotherapy protocols, combinations of two or more chemotherapeutic agents with different mechanisms of action, for example, vincristine, dactinomycin, doxorubicin, cyclophosphamide and isophosphamide, are usually prescribed [11]. Several studies have been conducted using various combinations of chemotherapeutic agents; however, even combinations with good initial responses do not improve the survival rate or the tumor recurrence rate in the long term [10].…”