Phase I/II study of the rituximab-EPOCT regimen in combination with granulocyte colony-stimulating factor in patients with relapsed or refractory follicular lymphoma including evaluation of its cardiotoxicity using B-type natriuretic peptide and troponin T levels.
OBJECTIVE
Standard treatment for relapsed or refractory follicular lymphoma has not been established. Doxorubicin is often given during the initial treatment. The dosage or drugs chosen for salvage therapy are limited by doxorubicin-induced cardiomyopathy.


METHODS
The R-EPOCT (rituximab with etoposide, vincristine, pirarubicine, cyclophosphamide, and prednisone) regimen, in which less cardiotoxic pirarubicine is used instead of doxorubicin, with granulocyte colony-stimulating factor (G-CSF) was administered to 20 patients with relapsed or refractory follicular lymphoma. The safety (especially cardiotoxicity) and efficacy of this regimen were studied. As markers of cardiotoxicity, serum troponin T and plasma B-type natriuretic peptide (BNP) levels were measured.


RESULTS
Adverse reactions occurred in 14 of the 20 patients and mainly consisted of grade 3/4 hematologic toxicity. In the evaluation of cardiotoxicity, the BNP level was slightly elevated before the treatment in two patients and the BNP level did not significantly increase after R-EPOCT treatment. The troponin T level was undetectable before and after the treatment in all patients. The response rate was 100%, with complete remission in 16 patients (80%). G-CSF administration increased both Fc gamma receptor type I expression on neutrophils and antibody-dependent cellular cytotoxicity activity. There were no significant differences in the levels of Fc gamma receptor type I expression nor antibody-dependent cellular cytotoxicity activity after three or five cycles of the treatment.


CONCLUSIONS
We conclude that the combination of R-EPOCT and G-CSF is well tolerated. This regimen was not cardiotoxic. We are planning a randomized trial to compare the efficacy between R-EPOCT and a combination of R-EPOCT with G-CSF.
Niitsu
Nozomi
N
Department of Hematology and Internal Medicine IV, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara-shi, Kanagawa 228-8555, Japan. nniitsu@med.kitasato-u.ac.jp
Khori
Mika
M
Hayama
Miyuki
M
Kajiwara
Koichi
K
Higashihara
Masaaki
M
Tamaru
Jun-ichi
J
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006331:Heart Diseases / Q000139:chemically induced* / Q000473:pathology; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D011241:Prednisone / Q000008:administration & dosage; D017452:Receptors, IgG / Q000378:metabolism; D012074:Remission Induction; D000069283:Rituximab; D016879:Salvage Therapy; D020107:Troponin T / Q000097:blood*; D014750:Vincristine / Q000008:administration & dosage
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D017452:Receptors, IgG; D020107:Troponin T; D020097:Natriuretic Peptide, Brain; D016179:Granulocyte Colony-Stimulating Factor; D000069283:Rituximab; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; C027260:pirarubicin; D011241:Prednisone