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AlaskaDeb

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Reply with quote  #1 

I need some help with some research.  I am on Avastin, Taxol and Zometa.  My mets are in my lymph system and "widespread" in my bone marrow, but with no visible lesions in the bone.

I have done my first 2 chemo treatments, the first one with all three drugs, last week, just Taxol.  I got my blood drawn yesterday and my white count is down to 2.9 and my nurtofills (sp) are down to 1.6

when I was on Taxol the first time I got cancer my counts did NOT go down.

Now for the questions.....

I have read that Nulasta can feed cancers in the bone.  Does anyone have a link to reasearch showing that?

Also, it makes sense to me that if the cancer is in my marrow, the bones will have a harder time making the white cells, so they may recover slower.  Does anyone know if that is really true?

We are drawing labs again today and are doing the chemo either way, but my doc thought we would do Nulasta if the counts drop....I'm not sure I want to do that.

Any info you can point me to would be appreciated.

Thanks

Deb C

 

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suzfive

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Reply with quote  #2 
Hi Deb,

I just Googled Neulasta and bone marrow mets and could not find anything that said that it could feed the cancer. I have heard just recently that cancer patients might want to think twice about getting Epogen or Aranesp for red cell counts because these two DO seem to feed the cancer (FDA just recently made them put a black box warning on these two). I started out very anemic and had to get Aranesp every two weeks throughout chemo - wish I had this information then.  I also Googled Avastin and low counts are one of the side effects listed so maybe that is what is causing you to have low counts now - the double whammy of both Avastin and Taxol.

I hope this helps.

Hugs,
Suz

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edge

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Reply with quote  #3 

Deb:

I am really impressed that you are aware of this issue, good for you!

The Issue of G-CSF-Induced Bone Tumor Promotion
The issue concerns the use of
G-CSF (granulocyte colony-stimulating factor) during chemotherapy via agents such as pegfilgrastim (Neulasta), filgrastim (Neupogen), and lenograstim (Granocyte). The study you're thinking of is an animal model that was conducted by senior author Katherine Weilbaecher and her colleagues at WUSM (Washington University School of Medicine) [Hirbe AC, Uluçkan O, Morgan EA, et al. Granulocyte colony-stimulating factor enhances bone tumor growth in mice in an osteoclast-dependent manner. Blood. 2007 Apr 15;109(8):3424-31 (use this link if you want to access the full text version)]. The WUSM team found that G-CSF administration induced:

  1. an increase in bone resorption (process of absorption and removal of old bone tissue) markers;
  2. an increase in osteoclastogenesis, which is the generation of osteoclasts, the cells associated with the bone resorption ("breakdown") process, inself part of the normal process of bone turnover (removal of old bone cells by new ones)
  3. promotion of significant bone loss, comparable in level and impact to that of oophorectomy in post-menopausal women,
  4. promotion of tumor growth in the bone marrow cavity.

Although the study explored G-CSF activity in the absence of concomitant chemotherapy, unlike the clinical practice of coadministration to ward off or mitigate the risk of (febrile) neutropenia (depressed white blood cell (WBC) levels) and associated risk of infection or sepsis, we already knew from previous studies that osteoclastogenesis appears to not only promote osteoporosis and increased risk of fracture, but also enhance tumor cell growth within bone (probably through disruption of a receptor called CXCR4). Indeed, bisphosphonates like zoledronic acid (Zometa), alendronate (Fosamax) and others work to decrease tumor burden within the bone by disrupting osteoclastogenesis which otherwise directly promotes tumor cell survival and growth.

To date the weight of the evidence, including this study, suggests that anything - like G-CSF - that encourages bone breakdown (resorption) or osteoporosis (a disorder of bone resorption) or decreases bone density, could potentially enhance tumor growth in bone, in this case by G-CSF–induced osteoclastogenesis which increases bone tumor burden.

Clinical Implications
What's not clear is whether G-CSF administration would have the same adverse effect in the presence of concurrent chemotherapy, since as the researchers acknowledge, it's theoretically possible that the increased osteoclastogenesis mediated by G-CSF might actually enhance the effectiveness of cytotoxic chemotherapy by increasing tumor cell proliferation and entry into the cell cycle in the bone marrow. This is suggested as a definite possibility by the authors since several RCTs studying G-CSF concomitantly with, and in support of, chemotherapy have not evidenced any adverse effect on survival or on bone metastases, in fact suggesting that women undergoing dose-dense chemotherapy with G-CSF support have increased DFS (disease-free survival) compared with standard - non dose-dense - chemotherapy dosing without G-CSF.

However, this is unconvincing: it strikes me on the evidence that this is almost certainly due more to the dose-density of the chemotherapy than to any contribution from the accompanying administration of G-CSF: after all, we know from the Norton-Hudis-Theodoulou-Triana research at MSKCC that dose-dense chemotherapy increases efficacy without increasing, generally minimizing, toxicity and tolerability. In addition, if bone metastases are involved, patient will almost invariably be on bisphosphonate therapy which inhibits osteoclastogenesis and hence it too, like dose-dense chemotherapy, may be overwhelming the negative impact of G-CSF in promotion bone marrow tumor growth, leading to overall favorable findings, which however may have been even more favorable had there been no accompanying G-CSF.

Clinical Pearl: What's It All Mean
Thus, this would suggest that patients be administered G-CSF therapy only for the shortest effective duration during dose-dense chemotherapy, and otherwise avoided, and wherever possible with concurrent active bisphosphonate therapy if motivated by patient bone health, to assist in overcoming any potentially adverse effects of G-CSF on osteoclastogenesis and bone tumor promotion. It also further strikes me that antibiotic prophylaxis along with G-CSF may help enhance the anti-neutropenic efficacy of G-CSF and hence help to shorten time on G-CSF or possibly even allow for somewhat lower dosing, as we know from recent findings from the GEPARTRIO study, among others, that pegfilgrastim (Neulasta) is more effective when supplemented with ciprofloxacin (Cipro) (500 mg orally twice daily on days 5–14 ). And my research in lung cancer also supports these findings: a recent EORTC study found that antibiotic prophylaxis with ciprofloxacin (Cipro) plus roxithromycin (Rulide), without any accompanying G-CSF, reduced the incidence of chemotherapy-induced infections and associated hospitalization by 50%, also reducing associated mortality; and the recent SIGNIFICANT (Simple Investigation in Neutropenic Individuals of the Frequency of Infection after Chemotherapy ± Antibiotic in a Number of Tumours) Trial at the University of Birmingham established that prophylactic levofloxacin (Levaquin) on cycle 1 only of myelosuppressive cancer chemotherapy (and on subsequent cycles after a cycle-1 fever) effectively reduced the incidence of febrile episodes regardless of age, performance status, or tumor type (including breast cancer).
 
My Guidance in Your Case
In your case, you're fortunately on bisphosphonate therapy in any case and that, coupled with being on active chemotherapy while G-CSF may be administered, should minimize the risk of any aggregate G-CSF-induced bone tumor promotion, although even here it is wise to use G-CSF only if absolutely necessary given the balance of the evidence suggesting potential bone tumor-stimulative activity.


Constantine Kaniklidis
Breast Cancer Watch
edge@evidencewatch.com

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