autologous blood and marrow transplantation - Blog Science ...

Repetitive High-Dose Therapy With
Peripheral Blood Progenitor Cell Support
for Metastatic and Locally Advanced Breast Cancer
H. Miles Prince, Michael J. Millward, David Blakey,
Priscilla Gales, Danny Rischin
Blood and Marrow Transplant Service, Division of Haematology and
Medical Oncology, Peter MacCallum Cancer Institute, Melbourne, Australia
ABSTRACT
We have treated 42 patients as part of phase I or II studies using three cycles of
high-dose chemotherapy delivered every 28 days, with each cycle supported by
peripheral blood progenitor cells (PBPCs) and granulocyte colony-stimulating
factor (G-CSF). Sufficient PBPCs were collected before the first cycle of high-dose
therapy and equally divided to support the consecutive cycles. The purpose of these
studies was to develop a suitable outpatient regimen for a subsequent phase III
study. Patients were prospectively entered into consecutive studies: trial 1 phase I
ITP study («=23), consisting of three cycles of high-dose ifosfamide (7.5-12.5
g/m 2
/cycle), thiotepa (200-350 mg/m 2
/cycle), and paclitaxel (175 mg/m 2
/cycle).
The dose-limiting toxicities were renal tubular acidosis (grade 3) and mucositis
(grade 4). Other relevant but non-dose-limiting toxicities were ifosfamide
encephalopathy (grade 3 and 4), enterocolitis (grade 4), and reversible interstitial
pneumonitis (grade 2). The recommended dose for phase II studies is ifosfamide 10
g/m 2
, thiotepa 350 mg/m 2
, and paclitaxel 175 mg/m 2
. In trial 2 phase II Isolex300i
CD34-selection study, at the doses identified in the phase I study and using
Isolex300i CD34-selection, eight patients have undergone repetitive high-dose
therapy (total of 19 cycles completed to date). Recovery was compared with that of
patients infused with unselected cells. CD34-selected patients had a moderate delay
in recovery to absolute neutrophil count (ANC) >0.5X10 9
/L (/>=0.0387) and
platelets >20X 10 9
/L (/>=0.0305) and >50X 10% (/>=0.0421). In trial 3, CTP study,
patients were treated immediately after determining the maximum tolerated dose
(MTD) of the ITP study. Cyclophosphamide (4 g/m 2
) replaced ifosfamide, since
the major toxicities observed in the ITP study were ifosfamide-related. For the
entire cohort of 42 patients (all studies combined), 109 of the planned 126
treatment cycles have been delivered. The median time to ANC >1.0X10 9
/L was
10 days (range 8-28), with no significant slowing in neutrophil recovery over the
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