ICE Chemotherapy and ABMT in Metastatic Breast Cancer 
Over the past year at NCI, we have completed a Phase I study of a 
new combination of high dose ifosfamide, CBDCA and etoposide (ICE) 
with ABMT support in relapsed lymphomas, breast and germ cell 
cancers. The goal of this study was to develop a well-tolerated and 
effective regimen through the selection of better tolerated 
alkylators which have steep dose response curves as well as by 
taking advantage of the potential synergy between etoposide, and 
ifosfamide and CBDCA. In our Phase I study the MTD of ICE was 
found to be ifosfamide 16 g/M2, CBDCA 1.8 g/M2 and etoposide 1.5 
g/M2 because of neurological and renal toxicity. In ICE, the dose of 
CBDCA is 2.7-fold higher than the comparably toxic dose of cisplatin 
used in other ABMT regimens (14). 
Thirty-four patients have undergone transplant over 11 dose levels 
of ICE, with 9 patients transplanted at the MTD. There have been 4 
peri-transplant deaths, with 3 due to chemotherapy toxicity; 2/2 at 
dose level 10 and 1/1 at level 11: 3/3 had grade 2 hepatic toxicity, 
3/3 had grade 3 renal toxicity, and 2/3 had grade 3 CNS toxicity at 
these dose levels (levels 10 and 11). Thus, the dose limiting 
toxicity of ICE is renal, hepatic and neurologic toxicity. Maximum 
toxicities at the MTD (dose level 9) were: 2/6 patients had grade 2 
renal toxicity, 6/6 patients had grade 1 hepatic toxicity, 4/6 
patients had grade 2 diarrhea and 5/6 patients had grade 2 
stomatitis. An encouraging response rate was achieved in the ICE 
Phase I study: 8 of 13 non-Hodgkins's lymphoma patients surviving 
BMT are in CCR with a median follow-up of 10 months; 4 of 5 
Hodgkin’s patients are in CCR with a median follow-up of 5 months; 
6 of 8 breast cancer patients achieved CR/PR; and 4 of 4 testicular 
patients achieved CR/PR. This 75% response rate compares 
favorably to the response rates reported in other ABMT trials (9-11). 
To date, it appears that the response rates and survival obtained 
with the high dose triple alkylator regimens, including cytoxan, 
etoposide, cisplatin, a regimen very similar to ICE, are 
approximately equivalent (9-11). 
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