Effects of Granulocyte Colony-stimulating Factor (G-CSF), Trastuzumab, and Vinorelbine on Immune Cell Function
Status:
Terminated
Trial end date:
2009-03-01
Target enrollment:
Participant gender:
Summary
Trastuzumab or Herceptin is an antibody directed against Her-2. Her-2 is a growth factor
receptor which is present on the tumors of 25% of patients with breast cancer. The addition
of trastuzumab to chemotherapy has been shown in a randomized clinical trial to increase the
response rate to chemotherapy, the duration of response to chemotherapy, and to improve the
duration of survival of patients with metastatic breast cancer. The anticancer mechanism of
action of trastuzumab is unknown, but it is possible that trastuzumab acts by promoting
antibody-dependent cell mediated cytotoxicity (ADCC), or direct killing of cancer cells by
immune cells, triggered by antibodies bound to the surface of the cancer cell. G-CSF is a
drug which is a growth factor for certain types of immune cells. G-CSF has two favorable
effects on ADCC. G-CSF increases the pool of circulating cancer-killing immune cells, and
G-CSF increases the strength of binding of cancer-killing immune cells to a specific part of
the antibody. Therefore, priming with G-CSF significantly increases the efficiency of ADCC,
and four days of treatment with G-CSF has been shown to optimize ADCC in some studies. Recent
data from the investigators' laboratory indicates that chemotherapy can augment ADCC directed
against tumor cells.
The investigators' hypothesis is that pre-treatment with the drug G-CSF would increase the
effectiveness of chemotherapy given with trastuzumab.