Intensified chemotherapy supported by DMSO-free peripheral blood progenitor cells in breast cancer patients.
BACKGROUND
The majority of high-dose chemotherapy (HDC)-related complications results from bone marrow aplasia, but the graft infusion per se may cause adverse reactions due to the injection of both dimethyl sulfoxide (DMSO) and cell lysis products. We evaluated the feasibility of a two-step chemotherapy regimen with peripheral blood progenitor cell (PBPC) support in association with a novel procedure to remove DMSO and products of cell lysis from the cryopreserved cells.


METHODS
Stage III and IV breast cancer patients received induction chemotherapy with three cycles of CEF (cyclophosphamide 600 mg/m2, epirubicin 100 mg/m2, 5-fluorouracil 600 mg/m2) followed by three cycles of HDC consisting of escalating doses of cyclophosphamide (dose range 1200 3000 mg/m2) and carboplatin (dose range 600-1000 mg/m2), supported by DMSO-free PBPC reinfusion. DMSO was removed by a washing/enzymatic digestion procedure.


RESULTS
Twenty patients received induction chemotherapy and eighteen completed the entire chemotherapy program; a total of fifty-four cycles of HDC were administered. Dose limiting toxicity of HDC was long-lasting grade 4 neutropenia associated with documented infection. The maximum tolerated dose (MTD) was cyclophosphamide 3000 mg/m2 and carboplatin 600 mg/m2. No side effects related to PBPC reinfusion were observed.


CONCLUSIONS
The proposed two-step chemotherapy regimen, associated with a novel washing/enzymatic digestion procedure, is feasible in advanced breast cancer patients in the absence of complications related to the specific toxicity of PBPC reinfusion.
Del Mastro
L
L
Department of Medical Oncology, National Cancer Research Institute, Genoa, Italy. ldelmast@hp380.ist.unige.it
Venturini
M
M
Viscoli
C
C
Bergaglio
M
M
Signorini
A
A
Bighin
C
C
Bertelli
G
G
Semino
C
C
Pietra
G
G
Bertoglio
S
S
Sertoli
M R
MR
Lambiase
A
A
Rosso
R
R
Melioli
G
G
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D016190:Carboplatin / Q000627:therapeutic use*; D002498:Centrifugation; D003131:Combined Modality Therapy; D003451:Cryoprotective Agents / Q000378:metabolism*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004121:Dimethyl Sulfoxide / Q000378:metabolism*; D015251:Epirubicin / Q000627:therapeutic use*; D005260:Female; D000069585:Filgrastim; D005472:Fluorouracil / Q000627:therapeutic use*; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011994:Recombinant Proteins; D012074:Remission Induction / Q000379:methods; D016896:Treatment Outcome
D003451:Cryoprotective Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D003520:Cyclophosphamide; D016190:Carboplatin; D000069585:Filgrastim; D005472:Fluorouracil; D004121:Dimethyl Sulfoxide