Neoadjuvant high dose chemotherapy plus peripheral blood progenitor cells in inflammatory breast cancer: a multicenter phase II pilot study.
OBJECTIVE
With the introduction of combined modality therapy, approximately 30% of patients with inflammatory breast cancer (IBC) are alive and free of disease at 5 years, but the lack of control of systemic disease continues to be the main reason for treatment failure. The importance of the response to primary chemotherapy and, in particular, complete tumor regression after primary chemotherapy have previously been described to be among the most reliable prognostic factors along with the dose intensity of doxorubicin.


METHODS
To evaluate pathologic response rate and toxicity of neoadjuvant high dose chemotherapy (HDCT) with autologous peripheral blood progenitor cell (PBPC) support in patients affected by IBC, 21 patients were enrolled in a study in which it was planned that they would receive 4 courses of epirubicin 150 mg/m(2) plus granulocyte colony-stimulating factor (G-CSF) as induction and mobilizing chemotherapy. Patients with non-progressive disease were intended to receive 2 consecutive courses of a combination of high doses of mitoxantrone 40 mg/m(2) , thiotepa 500 mg/m(2) and cyclophosphamide 200 mg/kg as a conditioning regimen.


RESULTS
PBPC collection was successful in 20/21 patients. Twelve patients received a single course of HDCT, whereas 7/20 patients underwent a double procedure. At a median follow up of 48 months, 20/21 patients were evaluable for toxicity and 19/21 for response. At surgery 4/19 patients (21%) had no evidence of viable tumor cells in the breast and in axillary nodes, while 4 (21%) and 11 patients (58%) had microscopic and macroscopic disease, respectively. Eight patients have relapsed (35%) so far at a median of 16 months (9-54) from diagnosis. Eleven patients remain alive without evidence of disease. Five out of 20 patients experienced severe cardiotoxicity with congestive heart failure (CHF) which was responsible for the only treatment-related death.


CONCLUSIONS
This neoadjuvant HDCT regimen seems to be very effective in terms of objective responses, but we observed a high rate of cardiotoxicity and only a few patients were able to receive the two planned courses of high dose chemotherapy.
Dazzi
C
C
Oncology and Hematology Department, Ospedale Santa Maria delle Croci, viale Randi 5, 48100 Ravenna, Italy. dazzicla@laserinforma.com
Cariello
A
A
Rosti
G
G
Tienghi
A
A
Molino
A
A
Sabbatini
R
R
Aieta
M
M
Frassineti
G L
GL
Vertogen
B
B
Giovanis
P
P
Marangolo
M
M
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000633:toxicity; D001943:Breast Neoplasms / Q000401:mortality / Q000628:therapy*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D003131:Combined Modality Therapy; D015251:Epirubicin / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000633:toxicity; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007249:Inflammation; D007937:Leukapheresis / Q000592:standards; D008875:Middle Aged; D010865:Pilot Projects; D016896:Treatment Outcome
D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin