The online version of this article (doi:10.1186/s13018-017-0544-9) contains supplementary material, which is available to authorized users.
Osteosarcoma 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.
We 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.
We 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.
We 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.
Additional file 1: Figure S1. Risk of bias graph of each included study. (EPS 2203 kb)13018_2017_544_MOESM1_ESM.eps
Additional file 2: Table S1. The league table of the network for the progression-free survival estimates the treatments according to their relative effects. (DOCX 19 kb)13018_2017_544_MOESM2_ESM.docx
Additional file 3: Figure S2. Comparison-adjusted funnel plots for assessing all outcomes. a. Progression-free survival; b. Overall survival, part one; c. Overall survival, part two. (EPS 888 kb)13018_2017_544_MOESM3_ESM.eps
Additional file 4: Table S2. The league table of the network for the overall survival estimates the treatments according to their relative effects for first part. (DOCX 14 kb)13018_2017_544_MOESM4_ESM.docx
Additional file 5: Table S3. The league table of the network for the overall survival estimates the treatments according to their relative effects for second part. (DOCX 14 kb)13018_2017_544_MOESM5_ESM.docx
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- Effectiveness of multi-drug regimen chemotherapy treatment in osteosarcoma patients: a network meta-analysis of randomized controlled trials
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