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FLLoriK

Angel
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Posts: 568
Reply with quote  #1 
Hi Edge...
Does it matter if you have Gemzar for 3 weeks and have one week off or have Gemzar every other week?
I tried to have:
week 1 Gemzar/Avastin
week 2 Gemzar/Zometa
blood and platelet counts too low for chemo
week 3 Gemzar/Avastin

My doctor wants to change the routine.
I'm concerned!!!
What doyou think?

edge

Chief of Research
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Posts: 1,129
Reply with quote  #2 
Lori:

The FDA-approved schedule for gemcitabine (Gemzar) dosing is 2 weeks on one week off (1250 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle), officially coadministered with paclitaxel (Taxol) although in a metastatic setting, Gemzar is flexibly combined off-protocol with a broad menu of agents, including with all the taxanes, with bevacizumab (Avastin), and with other third generation new cytotoxics like vinorelbine (Navelbine). The operating guideline is for patients should be monitored prior to each dose with a complete blood count, including differential counts (the goal being to maintain an absolute granulocyte count of 1500 x 106/L and a platelet count ¡Ý 100,000 x 106/L prior to each cycle), and Gemzar dosage adjustments for hematological toxicity are made based on the granulocyte and platelet counts taken on Day 8 of therapy: if marrow suppression is detected, Gemzar dosage is adjusted by 25% decrements depending on the count values, and it's dropped by 50% for any severe (Grade 3 or 4) non-hematological toxicity, although each clinician plays this by individual judgement.
 
As to schedules other than the label use of 2 weeks on / one week off, these are being explored in clinical trials currently recruiting by Lilly, so the optimal schedule hasn't been as yet settled. And although therefore no decisive determination has been established, I would hazard that a week on / week off schedule may be of higher benefit, extrapolating from emerging results with capecitabine (Xeloda) scheduling. I base this on the pioneer research being done by the Norton / Hudis teams at Memorial Sloan-Kettering Cancer Center (MSKCC), which although not yet reported, has found both dramatically superior efficacy and superior tolerability for this DD-CAP (dose-dense capecitabine (Xeloda)), and although of course gemcitabine (Gemzar) is not the same drug as capecitabine (Xeloda), both are prodrugs of 5-FU and so share some pharmacodynamics. We'll know when the Lilly trial reports but in the meantime, that would be my motivated preference, and it's based also on a complex but well-established mathematical model of metastatic progression and drug resistance.
 

Finally, I believe from your postings that the main target of your current therapy is liver metastases. In that context, I am in some agreement with Nancy Lin at Dana-Farber who stated her (extensive) experience in this arena in a recent interview earlier this year of treating most triple negative patients with multiple liver metastases with the well-established Miller protocol of paclitaxel (Taxol) + bevacizumab (Avastin), but Gemzar is a reasonable substitution for Taxol if there were previous progression on taxane therapy. Where I would differ, as Gina also has expressed, would be to favor nab-paclitaxel (Abraxane) in any regimen that includes a taxane, as it appears to be superior to both paclitaxel (Taxol) and docetaxel (Taxotere), and as I documented in my triple negative disease review, it has some molecular advantage (via the caveolin pathway) over the classical taxanes.

 
Where I would more significantly differ in judgment would be in a context where a patient was refractory / resistance to anthracyclines and taxanes, which I believe your clinical history might suggest. If this were indeed the case, then I would strongly favor the new recently approved fourth generation regimen of the epothilone ixabepilone (Ixempra) + capecitabine (Xeloda), which has uniquely shown for the first time a survival advantage in triple negative disease, and field experiences reported to me which I am aggregating in a case series sometimes show extensive reversal of metastatic disease, including hepatic, pleural and other distant involvement, even by as little as the third week, with good tolerability (and Xeloda dosing down to 825 mg/m2 twice daily is feasible for enhanced tolerability without efficacy compromise). And when there is multiple distal site involvement, I would favor a next-line optimal triplet regimen if there is not significant remission or stabilization after 4 - 6 weeks on the doublet regimen, leaving the Avastin to yield ixabepilone (Ixempra) + capecitabine (Xeloda) + bevacizumab (Avastin), to allow rapid and aggressive targeting of all disease, but a short trial of the ixabepilone (Ixempra) + capecitabine (Xeloda) doublet can tried first. Given the remarkable efficacy of Ixempra in triple negative disease, and the highly promising emerging results from other epothilones in trial, epothilone therapy appears to be emerging as a major breakthrough in triple negative disease.
 
As to timing, your oncologist may want to complete a short trial of dose-dose (week on / week off) Gemzar + Avastin therapy but stipulate some terminus condition by which to either see significant remission or stabilization, or to move on to another option as described above; I don't know how long you've already been on Gemzar (with interruptions), but it would probably be prudent to have in mind a cutoff so as to allow opportunity to explore other potentially effective interventions.
 
Hope this helps clarify both the dosing issue and the potential options at this juncture. Best fortune to you.
 


Constantine Kaniklidis
Breast Cancer Watch
edge@evidencewatch.com

FLLoriK

Angel
Registered:
Posts: 568
Reply with quote  #3 

Thank you for your reply. I agreed to do this regiment for 3 months. I think that is ample time to see some changes. Don't you?

edge

Chief of Research
Registered:
Posts: 1,129
Reply with quote  #4 

Lori:

My guideline is to give it 14 weeks, about 3 and a half months - I published data that shows that TTR (time to response) with both traditional chemotherapy and endocrine therapy runs about at this mean TTR value. Three months (12 weeks) is often just shy of the beginning of objective response and may prematurely and falsely declare inefficacy.


Constantine Kaniklidis
Breast Cancer Watch
edge@evidencewatch.com

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