The role of chemotherapy in the management of non-metastatic operable extremity osteosarcoma.

Original articles published between 1991-1996 were selected according to specified criteria, and reviewed to provide answers to nine important questions about the role of chemotherapy in the management of non-metastatic extremity osteosarcoma: (1) Does adjuvant chemotherapy improve survival? (2) Are the results of the Rosen T10 protocol reproducible in different settings? (3) Is chemotherapy with two of the most active drugs (DOX/DDP) an effective adjuvant treatment, and comparable to other multiagent regimens? (4) Does histological response to neoadjuvant chemotherapy correlate with reduced local recurrence and/or improved survival? (5) Does a change of chemotherapy for patients whose tumors show a poor histological response to chemotherapy improve survival? (6) Does chemotherapy given before surgery (neoadjuvant) improve survival? (7) Are certain drugs, or their method of administration (route, duration, total dose, dose intensity, pharmacokinetics) important in determining outcomes? (8) Can new agents such as Ifosfamide be incorporated into intensive multi-agent chemotherapy, and does this improve pathological response and/or survival? (9) Can dose intensity of treatment be increased with G-CSF? The brief answers to questions 1-3 and 7-9 are "Yes"; question 4 "Yes, but may be changing"; and questions 5, 6 "Not proven," and these are expanded in the text. Future directions for treatment of osteosarcoma are covered under the headings identification of new agents, dose intensification, circumvention of drug resistance, immunotherapy, and insulin-like growth factor.