Dosing and side-effects of ifosfamide plus mesna

Area of Science:

• Oncology
• Pharmacology
• Clinical Toxicology

Background:

• Ifosfamide (IFO) is a widely used chemotherapy agent for adult and pediatric tumors.
• Current clinical practice primarily uses short-time infusions of IFO over 2-5 days.
• Continuous intravenous infusion of IFO/mesna is an experimental but promising approach.

Purpose of the Study:

• To evaluate the toxicity profile of ifosfamide (IFO) and mesna in cancer treatment.
• To understand the relationship between IFO dosage, administration schedules, and adverse events.
• To identify risk factors for CNS and renal toxicity associated with IFO therapy.

Main Methods:

• Review of clinical practice and ongoing studies involving ifosfamide (IFO) and mesna.
• Analysis of dose-escalation and varied scheduling of IFO/mesna administration.
• Examination of reported cases of central nervous system (CNS) and renal toxicity, including Fanconi renal syndrome.

Main Results:

• Increased IFO doses (up to 16 g/m2) and varied schedules enhance CNS and renal toxicity.
• CNS toxicity appears linked to oral IFO dosing, with renal dysfunction and prior cisplatin use as predisposing factors.
• Nephrotoxicity, including Fanconi renal syndrome, is associated with cumulative IFO dose, prior cisplatin, and pediatric age.

Conclusions:

• Optimizing IFO/mesna dosage and schedules is crucial to minimize toxicity while maintaining efficacy.
• Further research is needed to establish the least nephrotoxic regimen for IFO/mesna.
• Dose-dependent side effects like leucopenia and thrombopenia occur with both short-time and continuous IFO infusions.