871 Low efficacy of 1 hour infusion-high dose ifosfamide (IFO) in previously pretreated sarcoma

Following Antman's report (Sem Onc 1990; 17: 7–15) underlining a better efficacy for fractionnated bolus Ifo infusion modality than the 24 h continuous infusion, as treatment in relapsing sarcoma patients, in October 93 we began a phase II study of high dose (HD) Ifo at 4 g/m 2 (d on 3 consecutive days (12 g/m 2 /cycle) given over 1 hour/d with Mesna (doses × 1. 5) every four weeks until progression. Twelve patients (pts) were entered, their characteristics as follows: median age 40 ys (18–62); sex 5 M/7 W; PS ≤ 1 12/12 pts; histologic types: bone sarcoma (sarc) 3 (2 osteosarc, 1 fibrosarc), soft tissue sarc 9 (synovialosarc 3, liposarc 2, other types 4). Ten pts had metastatic disease and 2 a locally advanced inoperable sarcoma. All pts were pretreated with chemotherapy, (1 regimen, (rg) 6 pts, 2 reg, 6 pts), the MAID regimen in 7 of them. Four/9 pts treated previously with intermediate dose Ifo 9 g/m 2 /cy (IDIFO) had responded to it. Results 35 cycles (cy) were administered, median number of cy/pt = 2 (1–6). All pts were evaluable for response. The only PR (8 weeks duration) was a previous complete responder to IDIFO. Of the 3 minor responders observed (median duration 3 months), one had previously responded to IDIFO. Seven pts had disease progression and there was one stabilisation. Toxicity/cy included: 7 febrile neutropenia episodes during the 1st cy, 2 of them despite G-CSF prophylaxis; all following cycles were administered with G-CSF; 1 grade 3 and 1 grade 2 thrombopenia, 1 grade 3 renal insufficiency, 1 grade 2 haemorrhagic cystitis. CNS toxicity related to treatment was seen in 1 cy (1 transient confusion). There was no dose modification, and no toxic death occurred. All treatment discontinuations were caused by progressive disease, or patient refusal (l pt). Conclusion Our experience with HOIFO (12 g/m 2 Icycle) contrasts with other reports showing a good efficacy of HDIFO in refractory sarcomas (Brain ASCO 95 A1641). Our series consists of pts pretreated with 1DIFO (9 g/m 2 /cycle) and our administration modality (1 hour instead of C. I. V.) may account for the 50% decrease of AUC and half life between the 1st and 3rd treatment days observed in our pharmacokinetic study (Lokiec et al. ASCO 95).