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Increase in Breast Cancer treatment related MDS when GCSF given with Chemo
By Dross at 2007-02-07 05:00
Increase in Breast Cancer treatment related MDS when GCSF given with Chemo

Please read the About Us section if you have been diagnosed with Treatment related MDS. Leave your questions in the forums and I will be happy to help you with the latest research.

 

    Women with breast cancer who receive compounds that stimulate white blood cell production to help their bodies better tolerate chemotherapyterm are at an increased risk of developing a type of leukemiaterm or a condition called myelodysplastic syndrome, according to a new study in the February 7 Journal of the National Cancer Institute.

 

The authors note that the absolute risk of the conditions is very small, but that risk should still be taken into consideration when making treatment decisions. The growth factors granulocyte or granulocyte-macrophage colony-stimulating factor (G-CSF or GM-CSF) have been used to reduce the risk of infections from neutropenia, an abnormally low count of a certain type of white blood cell that helps control infections. Chemotherapy destroys these cells, and it is difficult for the body to quickly replace them. However, there is some concern that these growth factors may keep cells alive that have been mutated by chemotherapy.

 

Ordinarily, certain cell processes would recognize such damage and instruct the cell to die, but growth factors may save the mutant cell, allowing it to develop into a cancer called acute myelocytic leukemia (AML). There's also concern about the risk of a disease called myelodysplastic syndrome (MDS), in which the bone marrow, which produces blood cells, does not function normally. Indeed, some studies have hinted that cancer patients who receive growth factors with chemotherapy may have an increased risk of these two diseases.

 

Dawn Hershman, M.D., of the Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center and New York Presbyterian Hospital, and colleagues set out to determine the association between G-CSF or GM-CSF use and the risk of AML or MDS among women treated with chemotherapy for early-stage breast cancer. Using a database that links cancer registry data from the Surveillance, Epidemiology, and End Results (SEER) program with data from Medicare, the researchers identified 5,510 women age 65 and older who were diagnosed with breast cancer and treated with chemotherapy between 1991 and 1999. A total of 906 (16%) were treated with at least one course of G-CSF (832), GM-CSF (29), or both (49). Among these 906 patients, 16 (1.77%) developed AML or MDS; among the 4,604 women who didn't get growth factor treatment, 48 (1.04%) developed one of the diseases. The authors calculated that women who received GM-CSF or G-CSF had twice the risk of developing AML or MDS as women not treated with the growth factors.

 

"Our study demonstrates that the elevated risk of AML or MDS associated with adjuvant chemotherapy may be further increased by the concurrent use of growth factors," the authors write. "It is unclear if the growth factors cause an increased risk or if the requirements for their use cause an increased risk; however, the absolute overall risk appeared to be small, even among the elderly patients we studied. Nevertheless, if further research confirms this finding, this risk should be factored into clinical decisions with regard to the use of growth factors." In an editorial, Ivo P. Touw, Ph.D., and Marijke Bontenbal, of the Erasmus University Medical Center Rotterdam in the Netherlands, review the possible biologic mechanisms for the increased risk, and point out that growth factor use has increased in recent years. They also note that the benefits of adjuvant chemotherapy for breast cancer may far outweigh any risk of a second cancer. "In clinical practice,  the benefits of adjuvant chemotherapy are of a different order of magnitude than the risk of secondary MDS or AML," they write. "Furthermore, given all the unknown factors, associations could be found that have no causal relationship. The evidence for a potential role of G-CSF in the onset of AML/MDS, derived from only a few retrospective studies, thus has to be qualified as hypothesis generating rather than conclusive."

 



4 comments | 8247 reads

by gdpawel on Tue, 2012-07-17 23:33
EPO is a natural substance made by the kidney. It stimulates the bone marrow to make red blood cells (it is literally a "growth factor"). Healthy adults are usually at about 15 grams a deciliter. When normal people take it, their blood gets too "thick" and they die of heart attacks and strokes.

But it now looks as if increasing the hemoglobin level above 12 is very risky with pharmaceutical EPO. Pharmaceutical EPO makes sludgy blood.

The anemia drugs, which boosts patients' counts of hemoglobin (a protein that carries oxygen in the blood), raise the danger of heart attacks, strokes and death at "high" doses. The FDA has said there is "serious" cardiovascular risks for patients who took "higher than recommended" doses of these drugs. Also, patients who don't respond well to initial anemia therapy (hyporesponders) are exposed to the highest heart risks.

These anemia drugs are approved to treat patients whose weakness and fatigue is caused by chronic kidney disease or by the side effects of cancer chemotherapy. They stimulate production of oxygen-carrying red blood cells, which can boost patients' energy and strength. The issue is over the drugs' safety on how big a dose to use to boost concentrations of hemoglobin. The FDA-approved level is doses sufficient to increase hemoglobin to a maximum of 12 grams a deciliter.

Blood transfusions are generally needed when patients slip to less than 8 grams. The adage of some physicians was that if some improvement in hemoglobin was good, higher levels of hemoglobin would even be better. However, clinical trials have shown the drugs can reduce the need for blood transfusions and improve the quality of life when used within the "original" dosing range.

New studies have raised questions whether these drugs might be harming patients. Those study results suggest the drugs may make the cancer worse. One such study published in the New England Journal of Medicine found that patients treated aggressively with Procrit had a higher risk of heart problems or death than those treated less aggressively.

And now there is emerging evidence that pharmaceutical EPO can feed the growth of tumors in cancer patients (it IS a "growth factor" afterall).

A “growth factor” is about twenty small proteins that attach to specific receptors on the surface of stem cells in bone marrow and promote differentiation and maturation of these cells into morphotic constituents of blood. And blood is a circulating tissue composed of fluid plasma and cells (red blood cells, white blood cells, platelets). Problems with blood composition or circulation can lead to downstream tissue (which is made up of cells) dysfunction.

The problem is that few drugs work the way oncologists think and few of them take the time to think through what it is they are using them for.

[url]http://cancerfocus.org/forum/showthread.php?t=294

by gdpawel on Wed, 2012-07-18 00:43
Breast cancer patients given colony stimulating factors to overcome chemotherapy-driven neutropenia have an increased risk of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), according to researchers.

When a patient undergoes chemotherapy, all dividing cell types are affected. Cancers are rapidly dividing cells and this is the property that chemotherapy looks to exploit. Unfortunately, since this is a non-targeted approach, several other dividing cells types in the body are also affected. White blood cells are one such affected group of cells along with Red blood cells and platelets (which are all derived from the Bone Marrow, which is a rapidly dividing cell type). This depression of WBC numbers is known as the Myelosuppressive effect. This usually ends up being the limiting factor on how much dosage a patient can withstand. If too many WBCs are destroyed, then it will lead to a weakened immune system and that will lead to secondary infections and sepsis. So to counter this, patients undergoing chemotherapy to treat breast cancer are given a supplement of a certain kind of growth factors called Cytokines that stimulate the growth of subtypes of white blood cells.

G-CSF (Granulocyte - Colony Stimulating Factor) and GM-CSF (Granulocyte Macrophage CSF) are commonly used to boost the numbers of Neutrophils and Macrophages. This approach is called Adjuvant Chemotherapy. Boosting the immune system this way provides the advantage that a higher chemotherapeutic dosage can be tolerated by the patient leading to higher chances of cancer remission. However, the long term effects of such treatments had not been studied until now. In a recent issue of the Journal of the National Cancer Institute, Dr. Dawn Hershman and colleagues report that there is an increased risk for certain types of white blood cell related cancers in patients that have undergone adjuvant chemotherapy. They found that "The hazard rate ratio for AML or MDS among those treated with G-CSF or GM-CSF compared with those who were not was 2.14 (95% confidence interval [CI] = 1.12 to 4.08)". What this means is that adjuvant chemotherapy roughly doubles the chance of developing AML (Acute Myeloid Leukemia) or MDS (Myelodysplastic Syndrome). The authors point out that the benefits of adjuvant chemotherapy massively outweigh the risks. The absolute risk of developing secondary cancer in patients that undergo regular chemotherapy is very low to start with (about 1%) and doubling a low risk still remains a low risk (2%).

References:

1. Hershman D, Neugut AI, Jacobson JS, Wang J, Tsai W-Y, McBride R, et al. Acute myeloid leukemia or myelodysplastic syndrome following use of granulocyte colony-stimulating factors during breast cancer adjuvant chemotherapy. J Natl Cancer Inst 2007;99:196205.

2. I. P. Touw and M. Bontenbal Granulocyte Colony-Stimulating Factor: Key (F)actor or Innocent Bystander in the Development of Secondary Myeloid Malignancy? J Natl Cancer Inst, February 7, 2007; 99(3): 183 - 186.

[url]http://www.medpagetoday.com/HematologyOncology/BreastCancer/5007

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