title: Treatment of advanced, high-grade soft-tissue sarcoma with ifosfamide and continuous-infusion etoposide.
abstract: A total of 33 patients (median age, 44 years) with high-grade, adult soft-tissue sarcoma were treated with etoposide given at 600 mg/m2 in a 72-h continuous infusion and ifosfamide given at 1500 mg/m2 per day for 3 days every 3 weeks. Dose escalation/reduction was protocolled depending on the level of hematological toxicity observed in the preceding course. Overall, 90% of patients had metastatic disease, and the most common histologies were malignant fibrous histiocytoma and leiomyosarcoma. A median of 5 (range, 1-9) courses were given. Of 30 patients who were evaluable for response, 12 (40%) obtained a partial remission, and the median time to progression was 8 (range, 4-13) months. Grade 3-4 leukopenia and thrombocytopenia were seen after 89% and 8% of the courses, respectively; neutropenic fever was seen in half of the patients (15% of courses); and 32% of courses had to be postponed by 7 days or more due to myelosuppression. Dose reduction to below the standard had to be performed in 46% of courses, and dose escalation was achieved in only 13%. The reduced toxicity seen after the addition of granulocyte colony-stimulating factor (G-CSF) in five patients indicates that growth-factor support may enhance the dose intensity of the regimen. The results indicate significant activity for this regimen in adult soft-tissue sarcoma, which may in part be a result of the escalated dose and prolonged mode of administration of the phase-specific agent etoposide. As a result of this pilot series, a phase II study with ifosfamide, etoposide, and G-CSF in advanced adult soft-tissue sarcoma has been initiated by the Scandinavian Sarcoma Group.
authors.affiliation: Department of Medical Oncology and Radiotherapy, Norwegian Radium Hospital, Oslo.
authors.forename: G
authors.initials: G
authors.lastname: Saeter
authors.forename: K
authors.initials: K
authors.lastname: Talle
authors.forename: O P
authors.initials: OP
authors.lastname: Solheim
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001803:Blood Transfusion; D005047:Etoposide / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D007970:Leukopenia / Q000139:chemically induced / Q000517:prevention & control; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control; D013997:Time Factors
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D007069:Ifosfamide