Sign up Calendar Latest Topics
 
 
 


Reply
  Author   Comment  
FLLoriK

Angel
Registered:
Posts: 568
Reply with quote  #1 
I was told to switch from Xeloda to either Gemzar or Navelbine. I have mets to bones and liver that I know of...just had CT scans so many there is more.
Do you have any insight about the switch. I was on Xeloda for 11 months and am presently on a three month break. 
nosurrender

Avatar / Picture

Moderator
Registered:
Posts: 7,476
Reply with quote  #2 
I am sure Constantine will be on later to answer this!!!
He is awesome!


__________________


WE WILL PREVAIL





edge

Chief of Research
Registered:
Posts: 1,129
Reply with quote  #3 

Lori:

Gina has unsurprisingly already weighed in on target with invaluable information in answer, in another thread (here), so I'll just add a slightly different perspective to address the issue of their role in metastatic disease. First, it's important to note some fundamentals: these three are known as third-generation cytotoxics (chemotherapy), after first generation regimens like CMF, second generation chemotherapy then being dominated by first anthracyclines (doxorubicin (Adriamycin) and then traditional taxanes (docetaxel (Taxotere) and paclitaxel (Taxol), and now the third generation which includes the three agents you mentioned, capecitabine (Xeloda), gemcitabine (Gemzar) and vinorelbine (Navelbine), as well as nab-paclitaxel (Abraxane) which although a taxane is different by an order of magnitude (if it were more affordable, I would predict use of traditional taxanes would be abandoned tomorrow). And the fourth generation of cytotoxics / chemotherapy just arrived at the beginning of this year with the approval of the first epothilone class agent ixabepilone (Ixempra), with a couple of other epothilones waiting in the wings.

Roughly, second generation agents, the anthracyclines and the taxanes, are more effective than first generation regimens like CMF, and with the taxanes generally being more effective than the anthracyclines. Third generation agents are at least as effective as second generation anthracyclines and taxanes, and Abraxane has been shown superior to traditional taxanes, while the other third generation agents Xeloda, Gemzar, and Navelbine have a well-deserved reputation of efficacy and high objective response in metastatic disease in particular, while the fourth generation Ixempra appears possibly to be evidencing superior benefit in metastatic disease to all previous generations of chemotherapy.

Within the group of Xeloda, Gemzar, and Navelbine, both Xeloda and Gemzar are what's called 5-FU prodrugs, being metabolized in part to the same 5-FU agent (the "F" in the CMF regimen), but although closely related in this way, they don't appears to be cross-resistant, so that someone who has progressed on Xeloda may still gain benefit on Gemzar. My own sense is to follow progression on Xeloda by first trying Navelbine because that is in a wholly different class, called Vinca alkaloids, so that there is an impression it may have a slightly greater likelihood of inducing a response after Xeloda than perhaps Gemzar would.

All three are some of our most effective chemotherapies for metastatic disease, although the evidence, as I presented in one of my newsletter reviews and as well as elsewhere in this forum, would support ixabepilone (Ixempra) as more outcome favorable than even these three exceptional agents. (I just finished a consult on a very advanced case of liver metastasis, one of several with similar positive outcome, that proved refractory to just about every other chemotherapy and was rapidly progressing: I advised ixabepilone (Ixempra) and fortunately the advice was accepted, and after just a few cycles of Ixempra all disease - which was impervious to all previous treatment and kept advancing - was stabilized (including bone mets), and most liver metastases were remitted altogether). I've documented elsewhere in this forum how the evidence supports Ixempra as of unique value in metastatic disease, and the only agent in history to prove effective after progression on our best agents, namely anthracyclines, taxanes and capecitabine (Xeloda). To my mind this represents something of a new era in chemotherapy, and Ixempra unlike other chemotherapy agents shows minimal propensity to drug resistance.

Hope this helps clarify the matter, and frame it in a perspective relevant to the treatment of metastatic disease.


Constantine Kaniklidis
Breast Cancer Watch
edge@evidencewatch.com

FLLoriK

Angel
Registered:
Posts: 568
Reply with quote  #4 
Thank you so much!
So what I think I am reading is that you suggest Xeloda, Navelbine, then Gemzar? correct?

Or should I just insist on Ixempra?

The vanity in me asks, will I lose my hair on Navelbine?
edge

Chief of Research
Registered:
Posts: 1,129
Reply with quote  #5 

Lori:

Actually two guidances:

  1. I favor ixabepilone (Ixempra) over all the other cytotoxics in progressive metastatic disease: in evidence-based oncology we essentially play the odds wherever the odds information (called hazard ratios) are available), and the weight of the evidence clearly establishes the highest likelihood both of getting a response, and of controlling or remitting the progressive disease, with Ixempra deployment.
  2. My second guidance is that whenever there is bone involvement plus at least one organ site (liver, lung or brain), then I favor - and again the weight of the evidence supports - doublet regimens (two agents) over monotherapy, so instead of Ixempra alone, ideally I would push for Ixempra + vinorelbine (Navelbine), and it is known that, like capecitabine (Xeloda), Navelbine can be deployed even when there is some disease-induced liver dysfunction.

If I had to guess, you may be on a three month hiatus in part because of some liver dysfunction (otherwise there would be little motivation to interrupting chemotherapy for this period), and I am also assuming - something you can confirm with your oncologist - that there was progression on capecitabine (Xeloda), and it is for that reason, assuming that is true, that I would favor Ixempra + Navelbine over the FDA prescribed regimen of Ixempra + Xeloda (which would normally otherwise be my first choice).

The goal of doublet therapy is to use an aggressive highly effective high-response combination regimen to control or remit the progressing disease quickly to mitigate the prospects of further organ or visceral involvement, and although aggressive, these doublet regimens are still quite tolerable.

That would be the avenue I would advise you discussing with your oncologist, and I would counsel initiating therapy as soon as possible to avoid having to deal with further disease advancement.

Best fortune to you, hope this helps clarify my position, based on the best evidence available.

Finally, alopecia (hair loss) is virtually unheard of on Navelbine (it is no more than 3% incidence); on Ixempra, it is higher (48% approximately), but it is rarely severe (complete) and generally no more than grade 1/2, meaning light and transient, with full return, and the odds are still in favor of your evading it (hypothermia is one option to reduce likelihood still further, that is, a cold cap).


Constantine Kaniklidis
Breast Cancer Watch
edge@evidencewatch.com

Previous Topic | Next Topic
Print
Reply

Quick Navigation:

Easily create a Forum Website with Website Toolbox.