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

Abstract

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.

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

“…Neoadjuvant and adjuvant chemotherapy combined with resection has become the basic strategy for the treatment of osteosarcoma [47]. Neoadjuvant chemotherapy includes the addition of chemotherapy drugs before resection, and this regimen has the following advantages: (1) It can control the primary tumor and reduce the chance of surgical tumor invasion.…”

Deep RNA sequencing reveals the dynamic regulation of miRNA, lncRNAs, and mRNAs in osteosarcoma tumorigenesis and pulmonary metastasis

“…Osteosarcoma (OS) is one of the main primary malignant bone tumor subtypes which mostly occurs in adolescents at sites of rapid bone growth 1 . Although intensive efforts to improve both chemotherapeutics and surgical management have been made, the high local aggressiveness and rapid metastasizing potential to lung results in poor survival for patients with OS.…”

Combination of Osthole and Cisplatin Against Rhabdomyosarcoma TE671 Cells Yielded Additive Pharmacologic Interaction by Means of Isobolographic Analysis

“…cancers of soft tissue, bones (2), muscles, and sarcomas (3), including rhabdomyosarcoma (RMS) (4). RMS originating from mesenchymal stem cells develop malignant tumors of soft tissues located often in the head/neck and genitourinary system in children and adolescents causing aggressive disease and clinical complications (5).…”