Treatment of refractory osteosarcoma with fractionated cyclophosphamide and etoposide

J Pediatr Hematol Oncol. 2002 May;24(4):250-5. doi: 10.1097/00043426-200205000-00006.


Purpose: Standard multiagent chemotherapy for osteosarcoma may include platinum compounds, doxorubicin, and high-dose methotrexate. By identifying new chemotherapeutic strategies, the outcome of these patients can be improved and the toxicity of treatment regimens decreased.

Patients and methods: The authors evaluated the activity of the combination of cyclophosphamide (500 mg/m2 per day for 5 days) and etoposide (100 mg/m2 per day for 5 days) given with granulocyte colony-stimulating factor (G-CSF) to children with osteosarcoma unresponsive to conventional treatment.

Results: Fourteen patients with refractory osteosarcoma were treated with this combination. Twelve patients had been previously treated with a multiagent regimen that included carboplatin, ifosfamide, methotrexate, and doxorubicin. Seven of 11 evaluable patients had a poor histologic response in their primary tumor at the time of definitive surgery (Huvos grade 1 or 2). Sites of relapse included lung, bone, and brain. A total of 47 courses were given. An overall response rate of 28.5% was achieved. A complete response was obtained in one patient (7.1%), a partial response was obtained in three patients (21.4%), and stable disease for 1 to 4 months was achieved in five patients (35.7%). Five patients (35.7%) had progressive disease. Grade 4 neutropenia was the primary form of toxicity observed; the median duration of absolute neurophil count less than 500/microL was 4 days.

Conclusions: The combination of cyclophosphamide and etoposide resulted in a response rate of 28.5% in patients with refractory or relapsed osteosarcoma, and its incorporation into front-line therapies deserves further evaluation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Neoplasms / drug therapy*
  • Child
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Dose-Response Relationship, Drug
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Female
  • Humans
  • Male
  • Neoplasm Recurrence, Local / drug therapy
  • Osteosarcoma / drug therapy*
  • Retrospective Studies
  • Survival Rate
  • Treatment Outcome


  • Etoposide
  • Cyclophosphamide