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Attention Newbies: Important New Chemo Study

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dmwolf View Drop Down
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    Posted: Jan 12 2011 at 5:40pm

Newbies: you might want to discuss this study with your doctor as you work together to come up with a treatment plan.


Chemotherapy Sequence Affects Early Breast Cancer Outcomes

Elsevier Global Medical News. 2011 Jan 7, B Jancin

SAN ANTONIO (EGMN) — The sequence in which paclitaxel and anthracyclines are given for treatment of early breast cancer makes a big difference in long-term outcomes.

That's the conclusion reached in what is believed to be the largest-ever retrospective study of the clinical impact of the sequencing of taxanes and anthracyclines. The study involved 3,010 early breast cancer patients who were treated during 1994-2009 and entered into the prospective online database at the University of Texas M.D. Anderson Cancer Center, Houston.

The clear winner was paclitaxel, followed by anthracycline-based therapy with 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide or 5-fluorouracil, epirubicin, and cyclophosphamide, Dr. Ricardo H. Alvarez reported at the San Antonio Breast Cancer Symposium.

Starting with paclitaxel rather than an anthracycline-first regimen led to better long-term results in the settings of adjuvant chemotherapy and primary systemic (or neoadjuvant) therapy.

The adjuvant chemotherapy analysis included 1,596 women, three-quarters of whom received paclitaxel followed by anthracyclines. The 5-year relapse-free survival rate with this regimen was 88.8%, compared with 79.5% when anthracyclines were followed by paclitaxel. The 10-year relapse-free survival rates were 81.8% and 73.5%, respectively.

Five-year overall survival was 93.1% with paclitaxel followed by anthracyclines, compared with 83.2% for the reverse. The 10-year overall survival rates were 83.9% and 65.6%, respectively.

In a multivariate analysis that was stratified for potential confounders, including age, clinical stage, hormone receptor status, tumor grade, and era of diagnosis, the anthracyclines-first sequence was associated with a 67% increased risk of relapse (P less than .0001) and a 2.5-fold greater risk of mortality (P = .001), according to Dr. Alvarez, a medical oncologist at M.D. Anderson.

Among 1,414 patients who underwent neoadjuvant therapy, the 5-year relapse-free survival rate was 79.0% with the paclitaxel-first regimen vs. 61.2% with the anthracyclines-first regimen. Ten-year relapse-free survival occurred in 61.7% and 50.5%, respectively, of these patients.

Overall survival was 84.2% and 66.2% at 5 and 10 years, respectively, in patients who received paclitaxel followed by anthracyclines, compared with 71.3% and 53.4% in those who got anthracyclines first.

In a multivariate analysis, the anthracyclines-followed-by-paclitaxel sequence of neoadjuvant chemotherapy was associated with an adjusted 49% higher risk of relapse (P = .01) and a nonsignificant 28% increase in risk of all-cause mortality (P = .17), compared with the paclitaxel-first strategy.

The mechanism that accounts for the increased efficacy of taxane-first regimens for treatment of breast cancer is unclear, according to Dr. Alvarez.



Edited by dmwolf - Feb 16 2011 at 2:35pm
DX 2/08@43 stg II IDC; gr2,0 nodes. Neoadj chemo, first ACx2 (fail) then CarboTaxotereX6(better). Lump, Rads done 11/08; Clodronate. False alarm queen: PetCT lung & TM marker. NED. PBM w/recon 9/10.
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123Donna View Drop Down
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Jan 12 2011 at 7:28pm
Denise,

Thanks for posting this article.  It's the total opposite of what is usually prescribed.  Maybe tx protocol will change.

Donna
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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Post Options Post Options   Thanks (0) Thanks(0)   Quote tAugusta Quote  Post ReplyReply Direct Link To This Post Posted: Jan 12 2011 at 7:38pm
I scheduled to start chemo.  So scared. Told Dr. that my insurance wouldn't start tell Feb 1. she just called
today and said "changed my mind, won't treat, come back Feb 1" Just Don't wait for chemo!

Maybe blessing as her protocol was taxol last.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote zoomommy2 Quote  Post ReplyReply Direct Link To This Post Posted: Jan 12 2011 at 7:43pm
Thanks, Densie.  Like Donna said, it's the opposite of what most of us have gotten in the past!  Hmm, things are always changing thanks to studies that we participate in!
Lee in Denver
dx6/09,stageII,gr3,(L)mastectomy 7/09,ACx4,Taxolx7,Avastin study,gall bladder surgery 1/10,4/11 Stage 4, mets to lung, 4/11 Started Taxotere and Xeloda, 5/11 Taxotere stopped, off Xeloda
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Post Options Post Options   Thanks (0) Thanks(0)   Quote dmwolf Quote  Post ReplyReply Direct Link To This Post Posted: Jan 12 2011 at 8:16pm
It would be great if there was a way to 'pin' this thread so that it doesn't get lost with time.   Most oncologists will NOT be familiar with this result, probably for years until it makes its way into the guidelines, so it will be up to us to educate new patients so they can educate their doctors.  The gain in survival odds with this simple change in protocol is just huge. 

d


DX 2/08@43 stg II IDC; gr2,0 nodes. Neoadj chemo, first ACx2 (fail) then CarboTaxotereX6(better). Lump, Rads done 11/08; Clodronate. False alarm queen: PetCT lung & TM marker. NED. PBM w/recon 9/10.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote The Texas Woman Quote  Post ReplyReply Direct Link To This Post Posted: Jan 12 2011 at 8:50pm
MDAnderson does Taxol first. I started treatment Sept. '09 so they've been doing it that way for at least that long. Can't recommend them enough!

cher
Dx: 7/09 TN IDC Stage llB, T2, N1, Grade 3 and associated DCIS, BRCA Neg, Taxol x 12, FAC x 4, left mastectomy March 2010
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Post Options Post Options   Thanks (0) Thanks(0)   Quote mom&grandma Quote  Post ReplyReply Direct Link To This Post Posted: Jan 12 2011 at 9:46pm

This is so disturbing!  MD Anderson has known about this since at least 9/2009 but Dana Farber had my daughter do AC then T.  So annoying....

Bonnie, mom of Heather, age 32, Dx on 9/1/09 TN IDC Stage 1, 1.4 c, lumpectomy, 10/8/09, DD AC & T, 3/9/10 bilateral mastectomy and immediate reconstruction, BRCA 1/2-
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Jan 12 2011 at 9:48pm
If the data was available since 2009, why did it take over a year to publish the results? 


DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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Post Options Post Options   Thanks (0) Thanks(0)   Quote mom&grandma Quote  Post ReplyReply Direct Link To This Post Posted: Jan 12 2011 at 9:56pm
Just noticed patients who also had cytoxan were excluded.  Wonder why?
Bonnie, mom of Heather, age 32, Dx on 9/1/09 TN IDC Stage 1, 1.4 c, lumpectomy, 10/8/09, DD AC & T, 3/9/10 bilateral mastectomy and immediate reconstruction, BRCA 1/2-
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Post Options Post Options   Thanks (0) Thanks(0)   Quote The Texas Woman Quote  Post ReplyReply Direct Link To This Post Posted: Jan 12 2011 at 10:10pm
tAugusta, I waited five weeks to get into MDA, with the tumor visibly growing that whole time. Drove me crazy. Feb. 1 isn't so far away so hang in there. It is SO expensive to do on your own. And when you do get the insurance going, insist on Taxol first.

I'm sorry, Mom&Grandma, that your daughter's doctor did things differently. As much as I recommend MDA, my onc and I had to insist on radiation after surgery and chemo. The surgeon didn't think I needed it - and he is one of their top guys! That's why I haunt the boards, so I KNOW what I want to do. I am in charge of my own treatment! 

Good luck, everyone.

cher
Dx: 7/09 TN IDC Stage llB, T2, N1, Grade 3 and associated DCIS, BRCA Neg, Taxol x 12, FAC x 4, left mastectomy March 2010
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Jan 12 2011 at 11:06pm
Bonnie,

Cyclophosphamide is the generic for Cytoxan.


DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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Post Options Post Options   Thanks (0) Thanks(0)   Quote mom&grandma Quote  Post ReplyReply Direct Link To This Post Posted: Jan 12 2011 at 11:45pm
Is this the same study?
 
Clinical Outcome of Two Sequences of Administering Paclitaxel (P) and Anthracyclines (A) as Primary Systemic Therapy (PST) and Adjuvant Chemotherapy (ACT) in Breast Cancer (BC) Patients: A Retrospective Analysis from the M. D. Anderson Cancer Center (MDACC).

Alvarez RH, Bianchini G, Hsu L, Cristofanilli M, Esteva FJ, Pusztai L, Buzdar AU, Hortobagyi GN, Valero V. The University of Texas, M.D. Anderson Cancer Center, Houston; Fondazione IRCCS- Istituto Nazionale dei Tumori, Milan, Italy


Background: P- and A-based regimens are widely used as PST and ACT of early BC. It is unknown whether the efficacy of such combinations is affected by their sequence of administration. The purpose of this retrospective analysis was to assess the clinical outcome of two different sequences of P and A in pts receiving PST and ACT.
Methods: We analyzed 3,010 pts (1,414 PST and 1,596 ACT) with stage I - III BC treated between 1994 -2009. These pts were identified through our prospective online MDACC breast cancer database. Pts treated with trastuzumab, docetaxel or adriamycin/cyclophosphamide-regimen were excluded. Pathological complete response (pCR) was defined as no residual invasive disease in breast and ipsilateral axillary lymph nodes.
Results: PST cohort included 1.071 pts (75%) with clinical stage I-IIIA and 343 (24.2%) stage IIIB-IIIC BC; 1,188 pts (84%) received the sequence P→A and 226 pts (16%) A→P. In the PST cohort 958 pts (67.7%) and 161 (11.3%) had hormone-receptor (HR) positive (+) and HER-2 + BC, respectively. ACT cohort consisted of 1,503 pts (94%) with pathological stage I-IIIA and 93 (5.82%) stage IIIB-IIIC. 1,196 pts (75%) received the sequence P→A, and 400 pts (25%) A→P. In the ACT cohort 1,122 (70.3%) and 93 (3.9%) had HR+ and HER2+ BC, respectively. Both cohorts of pts were balanced by HR-status, clinical stage, and menopausal status. The combined p-values for ACT and PST cohorts were calculated and they were significant for both RFS (p=0.022) and OS (p=0.002). In univariate analysis the sequence A→P was associated with inferior outcome. In Cox multivariate analysis, after stratification for period at diagnosis and adjustment for age, clinical stage, HR status, grade, and LVI the A→P sequence administered as PST was associated with significantly higher risk of relapse (HR 1.49; CI 1.10-2.03; p=0.01) but not death (HR 1.28; CI 0.90-1.84; p=0.17). In the ACT cohort, the Cox multivariate analysis, after stratification for age, HR status, HER2 the sequence A→P was significantly associated with higher risk of death (HR 2.02; CI 1.33-3.06; p=0.001) but not relapse (HR 1.21; CI 0.82-1.79; p=0.33).
Conclusions: The P→A sequence compared to the A→P sequence is associated with lower risk of relapse and death in PST and ACT, respectively. This retrospective analysis is hypothesis-generating and should lead to a prospective randomized trial to compare the two sequences as PST or ACT in locally advanced or early BC, respectively.

Bonnie, mom of Heather, age 32, Dx on 9/1/09 TN IDC Stage 1, 1.4 c, lumpectomy, 10/8/09, DD AC & T, 3/9/10 bilateral mastectomy and immediate reconstruction, BRCA 1/2-
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Post Options Post Options   Thanks (0) Thanks(0)   Quote MsBliss Quote  Post ReplyReply Direct Link To This Post Posted: Jan 13 2011 at 5:12am
I've been gone from the forum and just saw this thread which touches on a subject that I have been concerned with for a long time.  I would like to add my two cents.
Here is my understanding of the reasons or mechanisms behind this finding.  Taxol has a tendency to do a few things which are problematic:  yes, it is a brilliant chemotherapy drug which has it's place, but it tends to increase the numbers of circulating tumor cells in cases for which there is tumor mass present; this process has been poorly studied or understood.  Secondarily, taxol, by virtue of it's mechanisms with regard to tubulin, increases the micro tentacles on circulating cancer cells.  The micro tentacles are the mechanism that cancer cells use to anchor into blood vessels and "set up shop".  The University of Maryland School of Medicine has shown that this mechanism happens and is problematic and so there are questions to be answered in this regard.  It may not be that giving taxol first works better as a consequence of sequential treatment; it may be that giving taxol first allows for Adria and Cytoxan to mop up these cells which have acquired unfavorable mechanisms as a direct result of taxol's effects on microtentacles.  If taxol is given last, there is no counter measure should there be circulating cancer cells which have acquired these aggressive mechanisms. 
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Post Options Post Options   Thanks (0) Thanks(0)   Quote krisa Quote  Post ReplyReply Direct Link To This Post Posted: Jan 13 2011 at 7:11am
Ms Bliss-
Fascinating information. For those who have started chemo AC/Taxol - perhaps inquire about adding a carbo after completing Taxol to kill the micro cancer cells.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote outnumbered Quote  Post ReplyReply Direct Link To This Post Posted: Jan 13 2011 at 9:46am
This is very interesting.  Two years ago the buzz was instead of 4 biweekly dose dense AC and 4 biweekly T, to do 4 biweekly AC and 12 weekly T. 
 
It makes a lot of sense what MsBliss says.  This is great for the newbies to have more info and to go to their oncs armed with data. 
 
Thanks!
~Sara

DX @ age 40 6/24/08 Stage 1 Grade 3 BRCA1+ 187delAG

BMX (nipple-areola-sparing) 8/5/08

Redo BMX (remove nipple and areola) w/ Lat Flap 7/6/09

BSO 9/3/09

NED since 08/05/2008
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Post Options Post Options   Thanks (0) Thanks(0)   Quote thenewme Quote  Post ReplyReply Direct Link To This Post Posted: Jan 13 2011 at 10:12am
Wow, definitely interesting information!  The progress in understanding is so encouraging, but if only it would happen faster... !

MsBliss- do you happen to have a link to the study you mention about the taxol micro-tentacles?  I had seen a news press release at http://wearecentralpa.com/fulltext-healthcast/?nxd_id=237187  but I can't seem to find the actual study and I'd love to read more about it.  Does anyone know?
DX: IDC/TNBC 11/08 5-cm Stage IIb Grade 3. Age 39. Double Mast 12/08 (prophy right) with tissue expanders . ACx4-Tx3. Suspicious IM node. 25 Rads. BRCA NEG.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Barbi Quote  Post ReplyReply Direct Link To This Post Posted: Jan 13 2011 at 10:20am
I am getting exactly what Outnumbered mentions above plus (12 weeks of cisplatin, 11 weeks of taxol as neoadjuvant therapy, followed by sx, rads, and 4 treatments of AC - once every 2 weeks).  I have to admit that although the above study indicates that further randomized studies are needed, I am glad to be having my taxol 1st.  And the Outnumbered's info makes me feel even better.  What I'm not sure of, when would you suggest/insist on another Pet/CT. My onc has negated the presx imaging, nobody wants to biopsy my supraclavicular nodes(much less remove them), and I would at some point like to know if all this struggling is worth it if you're not going to at least check to be sure these nodes are responding to tx. 
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lillie Quote  Post ReplyReply Direct Link To This Post Posted: Jan 13 2011 at 11:15am
In 2006 I got 4 dd A/C and then 4 dd Taxol and Gemzar. According to this study I would have benefitted by getting the taxol first. I was in a clinical trial so I will hope that the gemzar did some magic in the last 4 infusions. Any thoughts??

God Bless,
Lillie
Dx 6/06 age 65,IDC-TNBC
Stage IIb,Gr3,2cm,BRCA-
6/06 L/Mast/w/SNB,1of3 Nodes+
6/06 Axl. 9 nodes-
8/8 thru 11/15 Chemo (Clin-Trial) DD A/Cx4 -- DD taxol+gemzar x4
No Rads.
No RECON - 11/2015-9 yrs NED
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Post Options Post Options   Thanks (0) Thanks(0)   Quote godlovinmomof3 Quote  Post ReplyReply Direct Link To This Post Posted: Jan 13 2011 at 12:28pm

WOW, I learn something new every day.  I have just finished my second round of A/C which will be followed by 12 weekly taxol.  I am also in the avastin study, so maybe that will kill any stragglers.  My gut feeling is that I am getting the avastin, but who knows for sure.  Wis I would have known this 3 weeks ago before starting, but I still think there is hope with the avastin.  THANK YOU SO MUCH for posting on this site.  I must admit this site was so helpful and inspiring in the beginning days and weeks of my journey, but the last few weeks have been rough to read with all the recurrance and passing of two amazing ladies.  My husband all but forbid me to get on here again.   LOL  However I am thankful and feel blessed to have found you ALL!!!  Most people do not understand, they try to be comforting by saying "well if you have cancer, Breast is the best to have" and yes they have come a long way, but This TN monster is a whole different ball game so it seems.  THANK YOU ALL FOR POSTING AND FOR THIS SITE!!!

Diag - 11/9/2010
Stage 2b
single mastectomy 11/23/2010
clear margins
3.5cm tumor 2N grade 3
AC biweekly 12/23/2010
T weekly Feb/2011 finished 5/4
begin radiation 6/2/2011
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Post Options Post Options   Thanks (0) Thanks(0)   Quote dmwolf Quote  Post ReplyReply Direct Link To This Post Posted: Jan 13 2011 at 12:53pm
This would upset the clinical trial folk, but if you wanted to you could drop out of the trial, do your 12 taxol now, and then finish up with 2 AC.   It's not too late.
Just a thought,
d

DX 2/08@43 stg II IDC; gr2,0 nodes. Neoadj chemo, first ACx2 (fail) then CarboTaxotereX6(better). Lump, Rads done 11/08; Clodronate. False alarm queen: PetCT lung & TM marker. NED. PBM w/recon 9/10.
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