title: Adjuvant and neoadjuvant combination chemotherapy for osteogenic sarcoma.
abstract: OBJECTIVE
  The most recent developments regarding chemotherapy treatment of osteogenic sarcoma are reviewed, with special emphasis on prospective clinical trials and evaluations of late effects of chemotherapy.
  
  
  RESULTS
  In recent years, clinical research has essentially focused on possible refinements of the classic four-drug (methotrexate, cisplatin, doxorubicin and ifosfamide) therapy rather than investigating new drugs. It has been demonstrated that dose-intensification does not improve prognosis. Many investigators have evaluated late chemotherapy-related side effects, particularly in terms of cardiac, renal and auditive toxicity, risk of infertility and of second tumors. Recent findings recommend further studies to define the role of the immunostimulating agent muramyl tripeptide-phosphatidilethanolamine in osteosarcoma. Preclinical and phase II studies suggest an activity of mammalian target of rapamycin (mTOR) inhibitors in osteosarcoma, which also deserves further clinical studies.
  
  
  CONCLUSIONS
  At present, patients with nonmetastatic osteosarcoma of the extremity aged less than 40 years have an expected 5-year survival rate of 70% with a chemotherapy regimen based on methotrexate, cisplatin, doxorubicin and ifosfamide. Further improvement cannot be achieved by dose intensification of treatment and new strategies are required. Prolonged follow-up is mandatory due to the risk of late effects, second tumors and late relapse from osteosarcoma.
authors.affiliation: Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy. stefano.ferrari@ior.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
authors.forename: Emanuela
authors.initials: E
authors.lastname: Palmerini
mesh_terms: D000277:Adjuvants, Pharmaceutic; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D004359:Drug Therapy, Combination; D006801:Humans; D007069:Ifosfamide / Q000627:therapeutic use; D020360:Neoadjuvant Therapy; D012516:Osteosarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D013997:Time Factors
chemical_list: D000277:Adjuvants, Pharmaceutic; D018906:Antineoplastic Agents, Alkylating; D007069:Ifosfamide