932 High dose continuous infusion (CI) ifosfamide without hematopoietic support in heavily pretreated breast cancer (BC) and sarcoma (S) patients

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Ifosfamide (IFO) is an oxazophosphorine with a different activity and toxicity profile than cyclophosphamide. Its use together with uroprotective agents has allowed safe administration and dose-escalation. We report the results of a phase II trial of IFO at high doses in heavily pretreated BC and S patients. IFO was administered in a 168 hour CI through a central venous access, for a total dose of 14 g/m2 q3w. MESNA was administered together at equimolar doses. Ondansetron, 8 mg/8 h po was used as antiemetic treatment. No hematopoietic support was used. We included 10 BC and 14 S patients with disease progression during salvage chemotherapy at conventional doses. Mean previous lines of therapy 3 (range 1–5), 20 had received previous treatment with conventional-dose cyclophosphamide or IFO. All had received previous adriamycin. Median age 44 (range 18–62), 12 males and 12 females. Median number of cycle 3 (range 1–8) for a total of 81 cycles of therapy. Worst WHO grade toxic reaction for each patient: grade III–IV leukopenia in 65%, grade III nausea and vomiting in 40%, grade III neurotoxicity in 5%, grade II nephrotoxicity in 5%. Neurologic and renal toxicity were reversible. 9 patients were admitted for neutropenic fever, with two documented septic episodes. Treatment had to be discontinued in 2 patients after 2 cycles (1 renal toxicit); I gastro-intestinal GI-toxicity). 20 patients are evaluable for response (4 did not finish the first cycle of therapy, 3 for early disease progression, 1 for unacceptable GI toxicity). Partial responses in 2/8 (25%) BC, and in 3/12 (25%) S. No complete responses were recorded. 65% had disease stabilization, and 10% had disease progression. 3 with S and 1 BC underwent further high dose chemotherapy with transplantation after assessment of chemotherapy sensitivity with high-dose IFO. Median duration of response was 5 months. Median overall survival was 6 months (range 2–11+). In conclusion, CI of IFO for 168 hours is an active regimen in highly pretreated BC and S. The addition of hematopoietic growth factors and further antiemetic agents could improve the toxicity ofthis regimen. Additionally, this regimen could be combined with non-myelotoxic drugs.