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Agent Tested in Metastatic Breast Cancer

CancerWise - May 2007

Researchers are studying whether there are any benefits to combining a protein that boosts the immune system with the drug trastuzumab (Herceptin®) in women with metastatic breast cancer who have not responded to trastuzumab alone or with chemotherapy.

Goal of the study

The protocol is not expected to eliminate advanced disease, but researchers are studying whether the experimental treatment will prolong survival, says the study’s principal investigator, Naoto Ueno, M.D., Ph.D., an associate professor in
M. D. Anderson’s Department of Breast Medical Oncology and Department of Stem Cell Transplantation and Cellular Therapy.

The primary objective of the study is to measure the patient’s tumor response rate and one-year progression-free survival.

Significance of the study

The M. D. Anderson study is the first phase II clinical trial to pair trastuzumab with granulocyte-macrophage colony-stimulating factor (GM-CSF), a protein that stimulates the production of white blood immune cells.

“This is an interesting use of trastuzumab because it tests the notion that trastuzumab may work in part by activating the immune system,” Ueno says. “Trastuzumab is typically used to inhibit tumor growth by binding to the outside of tumor cells. In this study, it combines with GM-CSF, another powerful immune stimulant, to rev up the body’s own ability to destroy unwanted cells.”

Study description

The 38 participants in the study will receive:

  • Trastuzumab weekly by intravenous (IV) infusion
  • GM-CSF daily by injection

Doses of GM-CSF may change depending on response. The experimental treatment will continue until diagnostic images show that tumors are growing and the disease is progressing.

Participants must be able to visit Houston for periodic treatments, and
M. D. Anderson oncologists also will work with a patient’s physician to ensure study medications are being administered, Ueno says.


To be considered for this study, patients must have:

  • Stage IV HER2-positive breast cancer
  • Measurable disease
  • Cancer that has progressed after treatment with either:
    • Trastuzumab
    • Trastuzumab plus chemotherapy
  • No active cancer that has spread to the brain


This trial is based on a pilot study conducted by Ueno, results of which were presented at the 2005 conference of the American Society of Clinical Oncology. The study found that cancer stabilized for a period of time in some patients with metastatic HER2-positive breast cancer.

The idea to pair trastuzumab with GM-CSF was borrowed from the use of GM-CSF with rituximab (Rituxan®), a drug approved by the U.S. Food and Drug Administration for the treatment of several types of non-Hodgkin’s lymphoma, Ueno says.

Trastuzumab and rituximab are monoclonal antibodies, proteins that cover the surface of cancer cells “like a sugar coating, making them attractive to the immune system,” Ueno says.

“Rituximab triggers an adaptive immune response called antibody-dependent cell-mediated cytotoxicity (ADCC), in which the immune system attacks a target cell bound by specific antibodies," he says. "Now, we are testing whether trastuzumab promotes ADCC, and if so, what the therapeutic benefit is.”

For more information, call askMDAnderson at 1-877-632-6789 and ask about protocol DM 01-0100.


© 2015 The University of Texas MD Anderson Cancer Center