title: The metronomic therapy with prednisone, etoposide, and cyclophosphamide reduces the serum levels of VEGF and circulating endothelial cells and improves response rates and progression-free survival in patients with relapsed or refractory non-Hodgkin's lymphoma.
abstract: There is an urgent need for a better strategy in the management of relapsed or refractory non-Hodgkin's lymphoma (NHL). The present study was designed to evaluate the efficacy and safety of the regimen using metronomic prednisone, etoposide, and cyclophosphamide in the treatment of patients with relapsed or refractory NHL, in comparison with conventional salvage chemotherapy.
  
  
  
  Eligible patients were randomized to the test group (n = 23) receiving metronomic prednisone, etoposide, and cyclophosphamide or the control group (n = 21) receiving conventional salvage chemotherapy. The serum levels of circulating endothelial cells (CECs) and vascular endothelial growth factor (VEGF) were measured before and after two cycles of treatment; overall response rate (ORR) and disease control rate (DCR) were evaluated at cycles 2, 4, 6, and 12 months after treatment.
  
  
  
  After two cycles of treatment, the ORRs of the test and control groups were statistically similar, while the DCR of the test group (87.0 %) was significantly higher than that of the control group (57.1 %). At 12 months after treatment, the ORR and DCR of the test group (47.8 and 69.6 %, respectively) were significantly higher than that of the control group (19.0 and 33.3 %, respectively). The serum CECs and VEGF levels in the test group after treatment were significantly lower than that before treatment or that of the control group. In the patients with ORR and DCR in the test group, the serum CECs and VEGF levels remained relatively low at cycles 2, 4, and 6 and at 12 months after treatment. There was a progression-free survival (PFS) benefit of 6.5 months in the test group, compared with the control group.
  
  
  
  Metronomic chemotherapy with prednisone, etoposide, and cyclophosphamide resulted in higher ORR and DCR, fewer adverse effects, and longer PFS in patients with relapsed or refractory NHL, with significant reduction in serum CECs and VEGF levels.
authors: Department of Medical Oncology, Affiliated Hospital of Hainan Medical College, Hainan Medical College Cancer Institute, Haikou, 570102, People's Republic of China.
authors: Jiangzheng
authors: J
authors: Zeng
authors: Department of Hepatobiliary Surgery, Affiliated Hospital of Hainan Medical College, Haikou, 570102, People's Republic of China.
authors: Liangxia
authors: L
authors: Yang
authors: Department of Medical Oncology, Affiliated Hospital of Hainan Medical College, Hainan Medical College Cancer Institute, Haikou, 570102, People's Republic of China.
authors: Fen
authors: F
authors: Huang
authors: Department of Medical Oncology, Affiliated Hospital of Hainan Medical College, Hainan Medical College Cancer Institute, Haikou, 570102, People's Republic of China.
authors: Tao
authors: T
authors: Hong
authors: Department of Medical Oncology, Affiliated Hospital of Hainan Medical College, Hainan Medical College Cancer Institute, Haikou, 570102, People's Republic of China.
authors: Zhihui
authors: Z
authors: He
authors: Department of Medical Oncology, Affiliated Hospital of Hainan Medical College, Hainan Medical College Cancer Institute, Haikou, 570102, People's Republic of China.
authors: Junhua
authors: J
authors: Lei
authors: Department of Medical Oncology, Affiliated Hospital of Hainan Medical College, Hainan Medical College Cancer Institute, Haikou, 570102, People's Republic of China.
authors: Huamao
authors: H
authors: Sun
authors: Department of Medical Oncology, Affiliated Hospital of Hainan Medical College, Hainan Medical College Cancer Institute, Haikou, 570102, People's Republic of China. luyandajx@sina.com.
authors: Yanda
authors: Y
authors: Lu
authors: Department of Medical Oncology, Affiliated Hospital of Hainan Medical College, Hainan Medical College Cancer Institute, Haikou, 570102, People's Republic of China. 59334462@qq.com.
authors: Xinbao
authors: X
authors: Hao
mesh_terms: D059250:Administration, Metronomic; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D042783:Endothelial Cells / Q000187:drug effects*; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D012008:Recurrence; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D018931:Antineoplastic Agents, Hormonal; D000972:Antineoplastic Agents, Phytogenic; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D005047:Etoposide; D003520:Cyclophosphamide; D011241:Prednisone
keywords: Circulating endothelial cells; Metronomic chemotherapy; Relapsed or refractory non-Hodgkin’s lymphoma; Tumor angiogenesis; VEGF