Myeloprotective effect of early primary granulocyte-colony stimulating factor during six courses of intensified 5-fluorouracil, epirubicin and cyclophosphamide (120FEC) chemotherapy for advanced breast cancer. Cooperative Group of Study and Treatment of Breast Cancer.
OBJECTIVE
The neutropenia induced by six courses of an intensified FEC regimen is expected to be checked by early primary administration of G-CSF which is stopped eight days before the next chemotherapy course. Less information is available about megakaryocytic and erythroid toxicity over six courses.


METHODS
Sixty-six consecutive patients with metastatic breast cancer completed six courses of a randomized treatment with two FEC regimens administered every 21 days, in which 600 mg/m2 of cyclophosphamide and 5-FUwas associated with 60 or 120 mg/m2 of epirubicin (60FEC, 35 patients, vs 120FEC, 31 patients). 120FEC was supported by early primary G-CSF (days 4 to 13). Blood counts were obtained seven times during each course.


RESULTS
The non-hematologic toxicity over 364 courses was similar in 60FEC and 120FEC. No cumulative hematologic toxicity was observed for white blood cells (WBC) and platelets (PLT), while for hemoglobin (Hb) a somewhat higher cumulative toxicity was observed with 120FEC than with 60FEC. WBC, PLT and Hb grade III-IV toxicity occurred in 40.1% and 45.6% (P=ns), in 23.1% and 0.8% (P <.0001) and in 15.6% and 3.0% (P <.005) of the two regimens, respectively. There were no febrile or hemorrhagic episodes. The epirubicin relative dose intensity delivered was 1.95 in 120FEC with respect to 60FEC.


CONCLUSIONS
Our G-CSF schedule permitted to deliver six courses of 120FEC without any clinically relevant side effects. Grade III-IV leukopenia was similar with 120FEC and 60FEC, while grade III-IV thrombocytopenia and anemia occurred more often with 120FEC than with 60FEC.
Riccardi
A
A
Medicina Interna e Oncologia Medica, Università and IRCCS Policlinico San Matteo, Pavia, Italy. riccardi@mbox.medit.it
Brugnatelli
S
S
Giordano
M
M
Danova
M
M
Pugliese
P
P
Tinelli
C
C
Klersy
C
C
Richetti
A
A
Fava
S
S
Nastasi
G
G
Rinaldi
E
E
Fregoni
V
V
De Monte
A
A
Trotti
G
G
Bovio
A
A
Ascari
E
E
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001853:Bone Marrow / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome
D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil