Efficacy and safety of ifosfamide-based chemotherapy for osteosarcoma: a meta-analysis

Fan, Xiao-Liang; Cai, G F; Zhu, Liu-long; Ding, Guoming

doi:10.2147/dddt.s91217

Cited by 25 publications

(20 citation statements)

References 29 publications

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“…This more intensive preoperative regimen comprised two courses of cisplatinum and doxorubicin in addition to a high dose of methotrexate and bleomycin, cyclophosphamide, and dactinomycin [32]; it showed a better effect on prolonging the PFS of patients when combined with ifosfamide or vincristine. However, these results are partially supported by a previous view that ifosfamide-based chemotherapy significantly improves the PFS of osteosarcoma patients [7]. In the secondary outcome analysis, we also observed that the regimens with more types of drugs showed better results, but use of a transfer factor also showed advantages.…”

Section: Discussionsupporting

confidence: 85%

“…Several systematic reviews have examined osteosarcoma chemotherapy, but the results are controversial. A previous study suggested that ifosfamide-based chemotherapy could significantly improve the PFS and OS of osteosarcoma patients [7]. However, recent traditional meta-analyses have not determined whether ifosfamide application and chemotherapy have similar histological response rates and 5-year PFS and OS in non-metastatic and primary osteosarcoma patients; thus, ifosfamide is not recommended [8–10].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effectiveness of multi-drug regimen chemotherapy treatment in osteosarcoma patients: a network meta-analysis of randomized controlled trials

Wang¹,

Hong²,

Shou³

et al. 2017

J Orthop Surg Res

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BackgroundOsteosarcoma is the most common malignant bone tumour. Due to the high metastasis rate and drug resistance of this disease, multi-drug regimens are necessary to control tumour cells at various stages of the cell cycle, eliminate local or distant micrometastases, and reduce the emergence of drug-resistant cells. Many adjuvant chemotherapy protocols have shown different efficacies and controversial results. Therefore, we classified the types of drugs used for adjuvant chemotherapy and evaluated the differences between single- and multi-drug chemotherapy regimens using network meta-analysis. MethodsWe searched electronic databases, including PubMed (MEDLINE), EmBase, and the Cochrane Library, through November 2016 using the keywords “osteosarcoma”, “osteogenic sarcoma”, “chemotherapy”, and “random*” without language restrictions. The major outcome in the present analysis was progression-free survival (PFS), and the secondary outcome was overall survival (OS). We used a random effect network meta-analysis for mixed multiple treatment comparisons.ResultsWe included 23 articles assessing a total of 5742 patients in the present systematic review. The analysis of PFS indicated that the T12 protocol (including adriamycin, bleomycin, cyclophosphamide, dactinomycin, methotrexate, cisplatin) plays a more critical role in osteosarcoma treatment (surface under the cumulative ranking (SUCRA) probability 76.9%), with a better effect on prolonging the PFS of patients when combined with ifosfamide (94.1%) or vincristine (81.9%). For the analysis of OS, we separated the regimens to two groups, reflecting the disconnection. The T12 protocol plus vincristine (94.7%) or the removal of cisplatinum (89.4%) is most likely the best regimen.ConclusionsWe concluded that multi-drug regimens have a better effect on prolonging the PFS and OS of osteosarcoma patients, and the T12 protocol has a better effect on prolonging the PFS of osteosarcoma patients, particularly in combination with ifosfamide or vincristine. The OS analysis showed that the T12 protocol plus vincristine or the T12 protocol with the removal of cisplatinum might be a better regimen for improving the OS of patients. However, well-designed randomized controlled trials of chemotherapeutic protocols are still necessary.Electronic supplementary materialThe online version of this article (doi:10.1186/s13018-017-0544-9) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Effectiveness of multi-drug regimen chemotherapy treatment in osteosarcoma patients: a network meta-analysis of randomized controlled trials

Wang¹,

Hong²,

Shou³

et al. 2017

J Orthop Surg Res

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“…According to the results of this network analysis, chemotherapy improves the life-span of patients, and the multiple drugs integrated with IFO and etoposide showed optimal performance, with the lowest HR value when compared with placebo, and most of the treatment options presented a significant difference, which was also confirmed by its highest SUCRA values for all six indices. This conclusion agreed with the outcome of one previous meta-analysis, but stands in conflict with another at the same time, the reason for which might be the confinement of the latter analysis to preoperative chemotherapy and osteosarcoma of the extremities, having examining their overlapping randomized control trials [Fan et al, 2015;Su et al, 2015]. Furthermore, although there was lack of significant difference, the highest SUCRA value found in multiple drugs with IFO alone illustrated its efficiency in reducing the incidence of relapse and lung-metastasis.…”

Section: Discussionsupporting

confidence: 85%

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

Zhang

Yang

et al. 2017

J of Cellular Biochemistry

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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.

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“…In a phase II study of ifosfamide in the treatment of recurrent sarcomas in young people concluded by Magrath et al [37], patients who experienced relapse after standard therapies have shown remarkable responses when they were subjected to ifosfamide-based chemotherapy. In the meta-analysis of Fan et al [38], ifosfamide-based chemotherapy reduced the risk of death in patients with osteosarcoma by 17% (HR = 0.83, 95% CrI 0.70, 0.99; P = 0.034). Meta-analysis, the highest level of evidence, showed the efficacy of ifosfamide for osteosarcoma.…”

Section: Discussionmentioning

confidence: 98%

The efficacy and safety comparison of first-line chemotherapeutic agents (high-dose methotrexate, doxorubicin, cisplatin, and ifosfamide) for osteosarcoma: a network meta-analysis

Zhang

et al. 2020

J Orthop Surg Res

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Background: Osteosarcoma, a primary malignant bone tumor derived from mesenchymal tissue, is the most common type of pleomorphic tumor that occurs in children and adolescents. The aim of this study was to compare the efficacy and safety of high-dose methotrexate (M), doxorubicin (D), cisplatin (C), and ifosfamide (I) in the management of osteosarcoma. Methods: Electronic databases including PubMed, Cochrane Library, and Embase database were searched for studies published from when the databases were established to July 13, 2019. The network meta-analysis was performed using software R 3.3.2 and STATA version 41.0 after demographic and outcome data extraction. The ranks based on probabilities of interventions for each outcome were performed. In addition, the consistency of direct and indirect evidence was assessed by node splitting. Results: The network meta-analysis results revealed that MDCI had a significant lower hazard risk of overall survival [MDCI vs MDC: HR = 0.74, 95% CrI (0.23, 0.87); MDCI vs DC: HR = 0.60, 95% CrI (0.16, 0.92)]. In addition, MDCI had a clearly longer progression-free survival time than that of DC [MDCI: HR = 0.88, 95% CrI (0.46, 0.98)]. No significant difference was detected in MDC and DC in OS, PFS, and AEs. The probabilities of rank plot showed that MDCI ranked first in OS (73.12%) and PFS (52.43%). DC was the best treatment in safety, ranked first (75.43%). Conclusions: MDCI showed its superiority among all chemotherapeutic agents in relation to efficacy and safety, followed by MDC. In addition, MDCI was associated with an increased risk of AEs. According to our analysis, DC was less effective but safer for MDC and MDCI.

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Efficacy and safety of ifosfamide-based chemotherapy for osteosarcoma: a meta-analysis

Cited by 25 publications

References 29 publications

Effectiveness of multi-drug regimen chemotherapy treatment in osteosarcoma patients: a network meta-analysis of randomized controlled trials

Effectiveness of multi-drug regimen chemotherapy treatment in osteosarcoma patients: a network meta-analysis of randomized controlled trials

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

The efficacy and safety comparison of first-line chemotherapeutic agents (high-dose methotrexate, doxorubicin, cisplatin, and ifosfamide) for osteosarcoma: a network meta-analysis

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