Creatinine clearance and serum albumin as factors for encephalopathy with ambulatory 14-day infusional ifosfamide for advanced liposarcomas.

Abstract

10087 Background: Ifosfamide (IFO) has recognised activity in soft tissue sarcomas (STS). There is preliminary evidence for improved cytotoxicity utilising a prolonged 14 day infusional regimen of IFO (PIR) compared with the standard 3-day regimen. Since September 2008 the PIR has been used at the Royal Marsden Hospital, principally for advanced de-differentiated liposarcomas (D-LPS) and shows activity. For many pts PIR is well tolerated, however, we noted serious neurotoxicity and this retrospective review was undertaken to more accurately determine the toxicity profile and define potential predictors of toxicity. Methods: A retrospective analysis of the Royal Marsden Hospital sarcoma database was performed to identify all pts who received PIR. IFO was given via central access through an ambulatory pump at 1G/m2/day with mesna, for 14 days every 4 wks. Oral sodium bicarbonate was used to maintain alkaline urine, oral mesna for haematuria and thiamine for symptoms of encephalopathy. Baseline characteristics and toxicities were graded according to CTCAE-4. Baseline serum creatinine (sCr), creatinine clearance (CrCl), albumin, LDH, gender and PS were evaluated as predictors of toxicity. Results: 22 pts were treated with PIR; median age 56yrs (29-76), M:F=11:11, 17 with advanced D-LPS. At baseline: PS (0=1, 1=17, 2=4), sCR (Gr 0=19), CrCl (Gr 0=2, Gr1=11, Gr2=6), albumin (Gr0=14, Gr3=3). Median no cycles 2 (1-8) with 10 pts receiving only 1 cycle (5 stopping due to neurotoxicity). Ten patients developed encephalopathy (Gr3/4=6), 9 in cycle 1. Toxicity was otherwise tolerable, with Gr 2-3 nausea (15 pts) and vomiting (9 pts) and only 2 Gr 3 episodes of myelotoxicity for all cycles. Significant predictors of encephalopathy were decreased CrCl and low albumin. Conclusions: Prolonged infusional ifosfamide is well tolerated for most pts; however a significant number develop neurotoxicity. Baseline CrCl and albumin have both been shown to predict those most at risk. This regimen has significant clinical potential and this study allows early identification of those who may need dose reduction from the outset. These predictors will be incorporated into a phase II study of this regimen.