A phase I study of prolonged ambulatory infusion of Ifosfamide with oral mesna.
BACKGROUND
Oral mesna allows investigation of ifosfamide as a prolonged ambulatory infusion for dose-intense out-patient use.


METHODS
Cohorts of 3 patients received escalating doses of ifosfamide from 200 to 1,000 mg/m2/day as continuous ambulatory infusion with oral mesna at 30% of the ifosfamide dose every 6 h commencing 2 h prior to ifosfamide infusion as uroprotection on a 14-day schedule with cycles repeated every 28 days.


RESULTS
Fifteen patients received a median of three cycles. Dose-limiting toxicities with cycle 1 were lethargy and hepatotoxicity at 1,000 mg/m2/14 days. Transient transaminase elevation was seen at all dose levels. The other grade 3 toxicities were single episodes of anaemia, granulocytopenia, nausea and hypotension. The best response was stable disease in a patient with thyroid cancer.


CONCLUSIONS
Ambulatory infusion of 600 mg/m2 ifosfamide with 180 mg/m2 oral mesna was considered suitable for phase II trials and delivers dose-intense out-patient therapy without urotoxicity.
Olver
Ian
I
Royal Adelaide Hospital Cancer Center, Adelaide, Australia.
Keefe
Dorothy
D
Myers
Melinda
M
Caruso
Diana
D
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000553:Ambulatory Care / Q000379:methods*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000627:therapeutic use; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage* / Q000627:therapeutic use; D007262:Infusions, Intravenous; D008297:Male; D015080:Mesna / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D020011:Protective Agents / Q000008:administration & dosage* / Q000627:therapeutic use
D018906:Antineoplastic Agents, Alkylating; D020011:Protective Agents; D015080:Mesna; D007069:Ifosfamide