Journal of Clinical Oncology, Vol 12, 1842-1848, Copyright © 1994 by American Society of Clinical Oncology
Doxorubicin and cisplatin with granulocyte colony-stimulating factor as adjuvant chemotherapy for osteosarcoma: phase II trial of the European Osteosarcoma Intergroup
D Ornadel, RL Souhami, J Whelan, M Nooy, C Ruiz de Elvira, J Pringle, I Lewis, WP Steward, R George and J Bridgewater
Department of Oncology, Middlesex Hospital, London, United Kingdom.
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.