Prolonged disease control after myeloablative chemotherapy, autologous transplantation and immunotherapy in high-risk early breast cancer.
BACKGROUND
Failure to eradicate all cancer stem cells, lymphocytopenia, and high levels of vascular endothelial growth factor (VEGF) may explain the limited efficacy of high dose-chemotherapy (HDCT) with peripheral progenitor cell transplantation (PBPCT) in high-risk early breast cancer with more than 10 axillary nodes (HRBC).


METHODS
With the aim of increasing patient's lymphocyte count and reducing VEGF, wich could translate into an improved immune function and a better clinical outcome, patients with HRBC, received HDCT, PBPCT and immunotherapy with interleukin-2 (IL-2) and 13-cis retinoic acid (RA).


RESULTS
A total of 30 HRBC patients were entered into the study. Grade 4 hematological toxicity was universal, while major adverse effects of IL-2 were fever, rash and autoimmune reactions. After a median follow-up of 61 months, immune function improved with a statistically significant increase of lymphocyte count and a decrease in VEGF levels. This translated into an unexpected 5-year relapse-free and overall survival rates of 76% and 85%, respectively.


CONCLUSIONS
These data show that IL-2 and RA administration after HDCT and PBPCT is feasible and, as well as giving a statistically significant improvement in lymphocyte count and a decrease of VEGF, also seems to improve the expected clinical outcome.
Recchia
Francesco
F
Via Del Castagneto n. 15, 67056 Luco dei Marsi (AQ), Italy. frecchia1946@libero.it
Candeloro
Giampiero
G
Necozione
Stefano
S
Accorsi
Patrizia
P
Recchia
Cornelia Ortensia Carla
CO
Tombolini
Vincenzo
V
Rea
Silvio
S
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016516:CD4-CD8 Ratio; D018270:Carcinoma, Ductal, Breast / Q000276:immunology / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D016896:Treatment Outcome; D014212:Tretinoin / Q000627:therapeutic use*
D007376:Interleukin-2; D015251:Epirubicin; D014212:Tretinoin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate