The use of recombinant human granulocyte-macrophage colony-stimulating factor with combination chemotherapy in the treatment of advanced adult soft-tissue sarcomas: early results from the EORTC Soft-Tissue and Bone Sarcoma Group.
We gave the "optimal" dose of doxorubicin (75 mg/m2) with ifosfamide (5 g/m2), the two most active agents against metastatic soft-tissue sarcomas, in an attempt to determine the feasibility of administration of these doses in combination. To offset complications arising from the myelosuppression associated with this regimen, recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF, 250 micrograms/m2 daily) was given by subcutaneous injection during the intervals between courses of chemotherapy. In all, 111 patients with progressive metastatic soft-tissue sarcoma were entered, 104 of whom were eligible for preliminary analysis. Use of rhGM-CSF allowed full doses of chemotherapy to be given to the majority of patients, although cumulative thrombocytopenia became a dose-limiting toxicity during subsequent courses. Two treatment-related deaths occurred, one from presumed septicemia while the patient was at home and one as a result of cardiac failure. An overall response rate of 45% was achieved. The activity of this high-dose combination (with rhGM-CSF) will be compared with that of standard treatment doses in a future phase III randomized trial.
Steward
W P
WP
Beatson Oncology Centre, Western Infirmary, Glasgow, Scotland.
Verweij
J
J
Somers
R
R
Spooner
D
D
Kerbrat
P
P
Clavel
M
M
Crowther
D
D
Rouesse
J
J
Tursz
T
T
Tueni
E
E
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000517:prevention & control*; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D012509:Sarcoma / Q000188:drug therapy*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
D011994:Recombinant Proteins; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007069:Ifosfamide