title: Effectiveness of multi-drug regimen chemotherapy treatment in osteosarcoma patients: a network meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Oncology, the First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, the First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Medical Oncology, the First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Shou
authors.affiliation: Department of Medical Oncology, the First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, China.
authors.forename: Chunming
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Medical Oncology, the First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Miao
authors.affiliation: Department of Thoracic Surgery, the First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, No.157 Jinbi Road, Kunming City, 650032, Yunnan Province, China. wangping8766@sina.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D006801:Humans; D012516:Osteosarcoma / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents
keywords: Chemotherapy drugs; Meta-analysis; Osteosarcoma; Overall survival; Progression-free survival