The role of granulocyte colony-stimulating factor (filgrastim) in maintaining dose intensity during conventional-dose chemotherapy with ABVD in Hodgkin's disease.
BACKGROUND
The aim of the study was to evaluate the role and potential benefit of granulocyte colony-stimulating factor (G-CSF, Filgrastim), administered following cytotoxic chemotherapy with the ABVD regimen in Hodgkin's disease, in maintaining cycle schedule and dose intensity and in decreasing neutropenia and number of infections.


METHODS
Twenty-two patients affected by high-risk Hodgkin's disease (14 localized and 8 diffuse), aged 15 to 69 years (median, 34), were given ABVD chemotherapy for a total of 6 courses (for the purpose of this study, each single course of chemotherapy was considered as two 15-day periods). No patient was given G-CSF after the first cycle. After each cycle, G-CSF was administered only for: 1)absolute neutrophil count < 1 x 10(9)/L between cycles; 2) delay in cycle schedule due to an absolute neutrophil count < 1 x 10(9)/L on the planned day of treatment; or 3) fever or a documented infection, regardless the absolute neutrophil count. Once administered, G-CSF was maintained in the subsequent cycles.


RESULTS
Seventeen of 22 patients (77%) required the administration of G-CSF (5 micrograms/kg b.w.; a median of 5 doses/cycle); most of them (13/17) before the 5th dose of chemotherapy. The main reason for introducing G-CSF into therapy was neutropenia during the interval between courses (n = 4) or on the planned day of treatment (n = 11). Comparing 112 courses where G-CSF was not administered with 124 where it was, in the latter group we observed: 1) a significantly lower (P = 0.0002) incidence of cycle delays (0 vs 13), with a median delay of 7 days (5 to 11). The main reason for cycle delay was neutropenia (n = 13); 2) a greater dose intensity delivered to the patients while on G-CSF (100% vs 95.2 +/- 8.8%; P = 0.0001); 3) an absolute neutrophil count significantly higher at day 8 (P < 0.0001) and day 15 (P < 0.0001); 4) a significantly lower (P = 0.0003) incidence of neutropenia (2 vs. 17). No difference in the incidence of infections was observed between the two groups of cycles (P = 0.5889), but the duration and severity of the same were greater during chemotherapy without G-CSF, requiring antibiotic therapy and causing cycle delay.


CONCLUSIONS
In conclusion, our data suggest the use of Filgrastim in Hodgkin's disease also during conventional-dose chemotherapy with ABVD. It is not required from the first dose of therapy, but as soon as neutropenia appears between cycles or on the planned day of treatment. Then, its use allows maintenance of the chemotherapy schedule and dose intensity. It also decreases frequency, duration and severity of neutropenia and its sequelae.
Silvestri
F
F
Division of Hematology, University Hospital, Udine, Italy.
Fanin
R
R
Velisig
M
M
Barillari
G
G
Virgolini
L
L
Zaja
F
F
Russo
D
D
Baccarani
M
M
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006689:Hodgkin Disease / Q000188:drug therapy*; D006801:Humans; D017053:Infection Control / Q000379:methods; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome; D014747:Vinblastine; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D011994:Recombinant Proteins; D001761:Bleomycin; D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; D014747:Vinblastine; D003606:Dacarbazine; D004317:Doxorubicin; D000069585:Filgrastim