Bioavailability of subcutaneous ifosfamide and feasibility of continuous outpatient application in cancer patients.
The oxazaphosphorine prodrug Ifosfamide (IFO) in conjunction with the uroprotective agent Mesna is becoming a standard alkylating agent. It has an increased therapeutic index when given as a fractionated dosage over 3-5 days. Maximal fractionation is achieved by continuous infusion over several days and has been shown to be less emetic and neurotoxic than regimens with bolus infusions. We have studied in patients with advanced cancer the feasibility and bioavailability of a subcutaneously administered isotonic and neutral (pH 7) IFO solution given continuously over 10 h for up to 5 days. A portable disposable gas-driven infusor syringe was used. Our results show 90-100% bioavailability of sc administered IFO. The isotonic solution of IFO (pH 7) showed no significant local toxicity during or after sc administration. Haematotoxicity was equal for sc and iv application. No uro- or neurotoxicity has been observed in 24 sc cycles. We conclude that this novel continuous sc IFO infusion over several days is a rational, well-tolerated and economical way of delivering this drug on an outpatient basis.
Cerny
T
T
Institut für Medizinische Onkologie, Universität Bern, Switzerland.
Küpfer
A
A
Zeugin
T
T
Brunner
K W
KW
D000368:Aged; D000553:Ambulatory Care; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001682:Biological Availability; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D015918:Infusion Pumps, Implantable; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D015080:Mesna / Q000008:administration & dosage; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D012509:Sarcoma / Q000188:drug therapy* / Q000378:metabolism; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000378:metabolism
D015080:Mesna; D007069:Ifosfamide