Interest for Stage IV Patients

tousled1 · 05-02-2007, 09:11 AM

Agent Tested in Metastatic Breast Cancer
Patients Resistant to Herceptin Take GM-CSF

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.

Criteria

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

Background

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-MDA-6789 (1-877-632-6789) and ask about protocol DM 01-0100.

StephN · 05-02-2007, 10:17 AM

Thought some of you might like to know that I took this combination along with Taxol and Navelbine for my very extensive liver mets.

The GM-CSF, otherwise known as Neupogen was part of ALL my treatments as part of the trials in 2001 and 2002. Without this white cell count builder I would have had to take less of my drugs and less often. With this added to my treatment I was able to stay on weekly infusion schedule for my mets.

My med onc considered the nightly injections (which I did) as an important part of my treatment.

I am not sure if I had mets again I would want ONLY Herceptin and the GM-CSF without some other kind of bomb for the active cancer. Their end point as stated in the article is ONE YEAR without progression. MY end point is a LIFETIME without my cancer progressing!

Becky · 05-02-2007, 07:36 PM

Actually GM-CSF is Leukine. Neopogen is G-CSF. It is Leukine that has the "macrophage" stimulation that is necessary for a self or pro vaccinating activity by boosting all components of the white blood cell system. Neopogen (and its sister Neulasta) only boost neutrophils.

Look at www.leukine.com to learn about this interesting drug. My use of it is in my signature. Since I was denied Herceptin at first, I depended on Leukine to give me that edge and who knows, maybe it did.

StephN · 05-03-2007, 12:11 AM

Now you made me go and dig around in my fridge.
I actually have a couple vials left of the "investigational drug" called Filgrastim or RHG-CSF by Amgen. This is the last that I used when fighting my mets.

So, this is not the same as Leukine (sargramostim).

Still, I am not sure I would personally want to fight mets with only Herceptin and the Leukine unless there were only a couple of small places. But that is not how my cancer moves when it activates! Can't help feeling that agressive mets needs an aggressive "push back."

Thanks for setting me straight.

Julie2 · 08-21-2007, 08:43 PM

Hi Becky,

I am interested to know about Lukine. Is this more expensive than Neulasta? Will the insurance companies allow the use of this drug instead of Neulasta without any problem?

Thanks,
Julie

Becky · 08-23-2007, 05:27 PM

My insurance company gave me no problem. It is not more or less expensive than Neulasta or Neupogen. It does have to be given daily vs Neulasta which is one shot that lasts 10 days. Neupogen has to be given daily too.

For more technical information www.leukine.com

It boosts the dendrites and the whole immune system. Too bad I didn't get taxol and herceptin together as I would have had leukine shots too and that would have been a great combo. Oh well! Glad to have gotten Herceptin no matter which way.

If you have to take a white blood cell booster - take Leukine. It has been used in bc metastatic settings and gave improved results.

If you take it, let me know - getting a hive or 2 at the injection site after the 6-10 dose is a good sign - shows that there is an immune responce. Good luck!