Reduction of ifosfamide toxicity using dose fractionation

Area of Science:

• Oncology
• Pharmacology
• Nephrology

Background:

• Ifosfamide is a chemotherapy agent used in cancer treatment.
• High doses of ifosfamide can lead to significant renal and bladder toxicity.
• Dose fractionation strategies are explored to mitigate chemotherapy-induced side effects.

Purpose of the Study:

• To investigate if dose fractionation of ifosfamide can reduce its toxicity.
• To evaluate the antitumor efficacy of fractionated ifosfamide administration.
• To assess the incidence of specific toxicities, including hematuria and azotemia.

Main Methods:

• Administered ifosfamide intravenously (IV) at doses of 600-1200 mg/sq m/day for 5 days to 32 refractory cancer patients.
• Monitored patients for renal function (azotemia) and bladder toxicity (hematuria).
• Assessed myelosuppression and other adverse events like nausea and confusion.

Main Results:

• Microscopic hematuria occurred in 14% and gross hematuria in 10% of patient trials.
• No instances of azotemia were observed.
• Reversible myelosuppression was comparable to existing data.
• Antitumor effects were observed in 7 out of 27 evaluable patients.
• Nausea and mental confusion were infrequent side effects.

Conclusions:

• Administering ifosfamide via IV infusions of 1-2 hours daily for 5 days substantially reduces renal and bladder toxicity.
• Dose fractionation appears to be an effective strategy for improving the safety profile of ifosfamide.
• The fractionated regimen demonstrated manageable toxicity and retained antitumor activity in refractory cancer patients.