Doxorubicin and cisplatin with granulocyte colony-stimulating factor as adjuvant chemotherapy for osteosarcoma: phase II trial of the European Osteosarcoma Intergroup

J Clin Oncol. 1994 Sep;12(9):1842-8. doi: 10.1200/JCO.1994.12.9.1842.

Abstract

Purpose: This report describes the toxicity and feasibility of administering doxorubicin (DOX) and cisplatin (CDDP) at 2-week intervals with granulocyte colony-stimulating factor (G-CSF) to patients with osteosarcoma and the compatibility of this regimen with endoprosthetic surgery performed after three cycles.

Patients and methods: Twenty-four patients with biopsy-proven osteosarcoma were treated with three preoperative cycles of DOX 25 mg/m2/d on days 1 to 3 and CDDP 100 mg/m2 on day 1 with G-CSF 5 micrograms/kg/d on days 4 to 14. Surgery was scheduled at week 6 to be followed by three further cycles of chemotherapy at 2-week intervals.

Results: Two-week chemotherapy was feasible, but delays and dose reductions only allowed 74% and 78% of the intended dose-intensity of DOX and CDDP to be administered. Thrombocytopenia accounted for 50% of delays. Significant toxicity included neutropenic sepsis, severe mucositis, prolonged nausea and vomiting, and electrolyte disturbances. Twenty-one limb-salvage procedures and one amputation were performed. There were eight episodes of excessive perioperative bleeding.

Conclusion: Intensive 2-week chemotherapy with intercurrent surgery is feasible and allows a greater dose-intensity of chemotherapy to be administered compared with the same regimen administered at 3-week intervals without G-CSF. The toxicity is considerable, but manageable.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Neoplasms / surgery
  • Bone Neoplasms / therapy*
  • Chemotherapy, Adjuvant
  • Child
  • Child, Preschool
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Europe
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Neutropenia / chemically induced
  • Neutropenia / prevention & control
  • Osteosarcoma / surgery
  • Osteosarcoma / therapy*
  • Thrombocytopenia / chemically induced

Substances

  • Granulocyte Colony-Stimulating Factor
  • Doxorubicin
  • Cisplatin