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FLLoriK

Angel
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Reply with quote  #1 
Well CT scans and bone scans are back.
Mets to liver, bone, lung, and kidney(new)

So off Ixempra I go and onto Doxil. Scared about that! But I only have Doxil, Abraxane, and Taxatore left as arsenal.

Taking a morphine pill and off to bed! 
DoreenF

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Reply with quote  #2 
Lori - I'm sooo sorry to read this sucky news ...  I'm confident that your doctors will find something that will help with your mets.  Have you thought about doing a trial ?  Has Constantine weighed in on what your other chemo options might be ?
Sending your lots of love, support and prayers for you and for your doctors!
Doreen


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Calico

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Reply with quote  #3 
Lori,
big hugs and lots of extra prayers for you!!!!
That sucks the big one.
Doxil should be kinder than Adriamycin I think, a better drug!!! revised.
How often will they check while you are on chemo, to see if it works?


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LisaSDCA

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Reply with quote  #4 
Lori -
I am betting this Doxil will kick butt! 
edge

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Reply with quote  #5 

[Posting repeated from The Cutting Edge forum for convenience ]

Lori:

 

A this point, I would agree to terminate ixabepilone  (Ixempra), but only because it was monotherapy (single-agent) in the first place: as you might know from my writings and my previous guidance, I do not ever advise monotherapy in progressive metastatic disease, and favor only multi-agent regimens (doublets and triplets typically).  The Cochrane meta-analysis by Cue Carrick and colleagues1 at the NHMRC Clinical Trials Centre (University of Sydney) of 28 randomized trials comparing single agent chemotherapy with combination therapy in women with MBC found a significant improvements in response rates and time-to-progression (TTP), along with a modest overall survival  advantage for combination chemotherapy compared to single-agent (mono)therapy, a finding that has been since confirmed.   

 

However, I would now prefer a new regimen than attempting to re-activate Ixempra with a combination approach.  And I am a strong advocate of the pegylated liposomal anthracycline Doxil, which is highly effective and with minimal cardiotoxicity.   But I especially advise it for another reason besides high response and effective outcome: as my latest review has documented, Doxil (as also capecitabine (Xeloda) is capable of crossing the blood-brain barrier and hence may be beneficial in mitigating against the development of CNS (brain and spinal) metastases.  

 

Designing an Optimal Oncotherapy Regimen

As to what to add to Doxil, there are three attractive options:

 

  1. As I recall, you are confirmably not a BRCA-mutation carrier (neither BRCA1 nor BRCA2), so a taxane is viable (in BRCA1 carriers, taxanes are of significantly compromised efficacy as I have documented), and the clear choice would be DD-Abraxane, that is, dose-dense, namely weekly, nab-paclitaxel (Abraxane) which is dramatically more effective than the standard taxanes (paclitaxel (Taxol) and docetaxel (Taxotere). 
  2. Despite having been used in the past gemcitabine (Gemzar) is still attractive, as there is a synergy with Doxil, and agents may be effective in combination regimens even if of limited value as single-agents, and GD (Gemzar + Doxil) has been used successfully in metastatic disease  by Edgardo Rivera and colleagues2at MD Anderson, achieving a high overall response rate of 58%, and the triplet of GDT (Gemzar + doxorubicin + Taxol) pushes the objective response rate to an extraordinary 82.9%, with a highly remarkable 43.9% complete response (no evidence of remaining disease), with tolerable toxicity, as Pedro Sanchez-Rovira and colleagues3 at the Hospital Ciudad de Jaén have recently shown, and indeed if GDT were implemented as Gemzar + Doxil + Abraxane, the expectation would be at least non-inferior, likely superior, results.
  3. As I again recall, you are endocrine-responsive, so a final attractive option is to add an endocrine agent with known efficacy in the metastatic setting, and I would strongly favor letrozole (Femara) as my first choice (with either the excellent antiestrogen toremifene (Fareston) or fulvestrant (Faslodex) as fallback).  Your progression on chemotherapy-only may be in part secondary to the absence of an endocrine component against endocrine-responsive disease such as yours.

 

Summary of Options
So in sum, the options I have outlined above are:

 

  1. Doxil + Abraxane
  2. Doxil + Gemzar (with or without a taxane component (Abraxane))
  3. Doxil + Femara

However, I would actually favor a fourth "cross-modality" approach of chemoendocrine therapy in the form of:

  1. Doxil + Abraxane + Femara

 

which I believe stands a superior chance of combating progression and remitting significant tumor burden, and with acceptable tolerability and high efficacy.


  1. Carrick S, Parker S, Wilcken N, et al. Single agent versus combination chemotherapy for metastatic breast cancer. Cochrane Database Syst Rev 2005: 2:CD003372.
  2. Rivera E, Valero V, Arun B, et al. Phase II study of pegylated liposomal doxorubicin in combination with gemcitabine in patients with metastatic breast cancer. J Clin Oncol 2003 Sep 1; 21(17):3249-54.
  3. Sánchez-Rovira P, Anton A,Margeli, M, et al.

Biweekly gemcitabine, doxorubicin and paclitaxel (GAT) regimen as neoadjuvant chemotherapy (NC) in locally advanced breast cancer (LABC) patients: Final results from 2002–01 GEICAM study. Proc Am Soc Clin Oncol. 2005;23:16s. Abstract 842.

 


Constantine Kaniklidis
Breast Cancer Watch
edge@evidencewatch.com 

 

nosurrender

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Reply with quote  #6 


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FLLoriK

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Reply with quote  #7 

Dear Edge, I am presently taking Zometa and Tomoxifen with the Ixempra. I wasn't addressed whether to stay on Zometa and Tomoxifen while on Doxil. Should I address it?

edge

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Reply with quote  #8 

Lori:

 

The Zometa should certainly be continued, but as there appears to be progression while on tamoxifen, and given that you already were exposed to Aromasin, my advice would be a switch to letrozole (Femara) which has an impressive reputation (with robust evidence) of efficacy in advanced and metastatic disease.  

 


Constantine Kaniklidis
Breast Cancer Watch
edge@evidencewatch.com 

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