autologous blood and marrow transplantation - Blog Science ...

322 Chapter 6: Breast Cancer
Table 6. Response to high-dose therapy
Pretransplant
response to Evaluable for Posttransplant status
conventional-dose response after CR
chemotherapy transplant CR (+bone scan) PR RR Stable Prog NE
Sensitive «=25 22 10 7 5 22/22 3*
(100%)
Resistant «=14 10 1 3 3 7/10 2 1 4t
(70%)
NE «=3 1 n 2
Total «=42 33 11/33 10/33 9/33 29/33 2/33 1/33
(33%) (30%) (27%) (88%) (6%) (3%)
*Three yet to complete planned treatment; fthree patients had locally advanced disease,
were refractory to conventional-dose chemotherapy, and had disease surgically resected
before high-dose therapy; one patient died of transplant-related toxicity and was not évalu­
able for response; tpatient had measurable disease before transplant, had mobilization
chemotherapy, and went directly to transplant (i.e., sensitivity to conventional-dose therapy
was not assessed).
promising, 26-28
our protocol did not incorporate these agents since we predicted
that the population of patients in our study were likely to have failed an anthracycline-based
regimen. Indeed this was the case, with 70% having received a prior
anthracycline. Instead, we designed a protocol incorporating conventional doses of
paclitaxel while focusing on the dose-escalation of the alkylating agents.
Ifosfamide dose-escalation. We selected two alkylating agents for our regimen;
ifosfamide and thiotepa. Ifosfamide has efficacy in advanced breast carcinoma, 29-33
and we anticipated that a number of patients eligible for this study would have
failed prior cyclophosphamide treatment. Although there is to date no conclusive
evidence that ifosfamide is superior to cyclophosphamide in the treatment of breast
cancer, preclinical data suggest it has potential advantages. 31,34-37
Taken together,
we believed it rational to use ifosfamide in our cohort of heavily pretreated
patients. High-dose ifosfamide has been used extensively as part of high-dose
conditioning regimens (usually with etoposide and carboplatin in the ICE regimen)
for the treatment of various malignancies. In these regimens, doses of 12.5-21 g/m 2
have been administered as part of a single transplant regimen, with doses of
10-12.5 g/m 2
used in double-transplant procedures. A major toxicity is the cortical
neurotoxicity (or ifosfamide-encephalopathy) which is caused by the metabolic
product of ifosfamide, chloracetaldehyde. Other toxicities include hemorrhagic
cystitis and renal tubular acidosis.