Standard treatment for relapsed or refractory follicular lymphoma has not been established. Doxorubicin (DXR) is often administered during the initial treatment. The dosage or drugs chosen for salvage therapy are limited by DXR-induced cardiomyopathy. Pirarubicine (THP) was developed in Japan as a less cardiotoxic and highly effective anti-neoplastic drug. We previously reported that the THP-COPBLM regimen, in which THP was used instead of DXR, showed the same degree of efficacy as the COP-BLAM regimen and that cardiac sympathetic dysfunction and cardiac mitochondrial damage were less common with THP than with DXR (
). The R-EPOCT (rituximab with etoposide, vincristine, THP, cyclophosphamide, and prednisone) regimen, in which less cardiotoxic THP is used instead of DXR, with 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. Adverse reactions occurred in 14 of the 20 patients, and mainly consisted of grade 3/4 hematological toxicity. In the evaluation of cardiotoxicity, the BNP level was slightly elevated in 2 patients before the treatment (22.4 pg/ml and 25.6 pg/ml; normal, less than 20 pg/ml). After 4 cycles of treatment, the BNP level in these two patients increased to 26.8 pg/ml and 28.8 pg/ml, respectively, but it returned to approximately the previous level one month after completion of 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 FcγRI expression on neutrophils and ADCC activity. Upon G-CSF administration during the second cycle of treatment, the level of FcγR1 (CD64) expression on neutrophils increased from 60.1 ± 3.6 (MFI) before G-CSF administration to 324.7 ± 33.2 (p = 0.0005) after 9 days of administration of 2 μg/kg G-CSF. After 11 days of G-CSF administration, the level of FcγR1 expression was 346.2 ± 24.2. The expression of FcαRI (CD89) on neutrophils was examined in a similar fashion. There was no remarkable change in the level of FcαRI expression before and after G-CSF administration. 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.
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