Increasing dose of continuous infusion ifosfamide and fixed dose of bolus epirubicin in soft tissue sarcomas. A study of the Italian group on rare tumors

• Published in: Tumori 1999-07, Vol.85 (4), p.229-233
• Main Authors: Frustaci, S, Buonadonna, A, Romanini, A, Comandone, A, Dalla Palma, M, Gamucci, T, Verusio, C, Lionetto, R, Dani, C, Casali, P, Santoro, A
• Format: Article
• Language: English
• Subjects: Adult; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - adverse effects; Antineoplastic Agents, Alkylating - administration & dosage; Antineoplastic Agents, Alkylating - adverse effects; Dose-Response Relationship, Drug; Drug Administration Schedule; Epirubicin - administration & dosage; Epirubicin - adverse effects; Female; Humans; Ifosfamide - administration & dosage; Ifosfamide - adverse effects; Infusions, Intravenous; Injections, Intravenous; Italy; Kidney - drug effects; Leukopenia - chemically induced; Male; Mesna - therapeutic use; Middle Aged; Peripheral Nervous System - drug effects; Protective Agents - therapeutic use; Sarcoma - drug therapy; Sarcoma - secondary; Thrombocytopenia - chemically induced; Treatment Outcome
• ISSN: 0300-8916; 2038-2529
• DOI: 10.1177/030089169908500403

To evaluate the maximum tolerated doses (MTD) of ifosfamide when given as a continuous infusion and in combination with fixed doses of bolus 4'-epidoxorubicin in advanced previously untreated adult soft tissue sarcoma patients. Treatment consisted of epidoxorubicin, 60 mg/m2 days one and two, and ifosfamide, 1.5 g/m2 every 12 hrs as a 72-hr infusion, at the first level. Further levels of ifosfamide were defined as increments of 12 hrs of the same infusion program. G-CSF 300 microg/die was administered from days +7 to +14. Dose-limiting toxicity (DLT) was defined as: G4 leukopenia or thrombocytopenia of > or =5 days; any G3 neuro or nephrotoxicity; G4 toxicity of any kind. Patients had to complete at least 2 consecutive cycles, and MTD was defined as the level in which 20% of patients developed a DLT; 10-15 patients were entered in each level. First level: overall, 13 patients entered, 3 were not assessable for MTD, and only one developed a DLT. Second level: 18 patients entered, 3 were not assessable for MTD. Hematologic DLT was observed in 3/15 assessable patients. Therefore, the MTD was found at the ifosfamide level of 10.5 g/m2 given in 84 hrs. Eight patients of 29 assessable for response achieved an objective response: 1 complete and 7 partial. The overall response rate was 28% (95% CI: 13-47%). If we accept 4-day G4 leukopenia as a reliable cutoff for safety, ifosfamide intensification cannot be substantially exploited over already available schedules with the combination of ifosfamide and anthracyclines.