IFOSFAMIDE TREATMENT AS A 10-DAY CONTINUOUS INTRAVENOUS-INFUSION

Experimental and clinical studies on ifosfamide indicate that fraction ated treatment regimens have a higher efficacy compared to a single sh ort-term infusion. In addition, protracted continuous infusion, in gen eral is often less toxic without loss of antitumour activity. To study the toxicity of a 10-day continuous infusion at increasing dosages of ifosfamide and mesna, 24 patients with a variety of advanced cancers (colon 10, pancreas 5, adenocarcinoma with unknown primary 5, and 4 ot hers) received a total of 60 cycles (range 1-6 cycles, median 2) at 3 to 4 week intervals. The ifosfamide and mesna doses ranged from 654 mg m(-2) day(-1) to 1562 mg m(-2) day(-1) for a total of ten doses. Twen ty-two patients were chemotherapy-naive. Pharmacia-Deltec CADD-1 pumps and Port-a-Cath implantable venous access devices were used. The dose -limiting toxicity was leucopenia without thrombocytopenia. At a dose of 1300 mg m(-2) day(-1) in 30% of the cycles in 7 patients leucopenia of WHO grades 3 and 4 was observed, while at higher dosages this perc entage increased to Haemoglobin values usually decreased during the in fusion with a mean of 1 mmol/l (range 0.3-2.5 mmol/l), frequently with partial or full recovery by the next cycle. The next most disturbing side-effect was fatigue (50% of patients WHO grades 2 and 3), and naus ea and vomiting requiring drug treatment in 75% of patients. Renal fai lure and haematuria did not occur. There were two catheter-related com plications: thrombosis (1 patient) and mechanical obstruction (1 patie nt). One patient developed severe encephalopathy at day 6 (total dose 18 g ifosfamide) with complete recovery after cessation of the infusio n. In summary, a tolerable ifosfamide dose using this regimen in this previously largely untreated patient group appears to be 1200-1300 mg m(-2) day(-1) for 10 days. Fatigue is a frequent complaint and might b e explained as a kind of neurotoxicity. The treatment can be administe red to outpatients.