herceptin & tykerb not my miracle combo

[Pam P]

Very discouraging news. After my 1st month of herceptin & tykerb my ca 2729 tumor marker has jumped up another 200 points in one month. My onc. said I can add aromasin to the mix so will start that now too and see if that makes a difference. He wants me to stay on this combo at least another month then review & depending on the marker maybe switch to herceptin/xeloda. I had good luck with that combo a few years ago, but of course no promise that it will work this time. So disappointing and scary to see that tumor number keep rising. It's up to 1691!

[Midwest Alice]

Oh Pam, I am so sorry. Xeloda worked before and I'm praying this combo will start those numbers back down.

[Rich66]

Seems to be more out there on combining Letrozole(Femara) with her2 therapy.

But if going aromasin route...


Tumori. 2009 Nov-Dec;95(6):804-7.
Inhibition of HER2/estrogen receptor cross-talk, probable relation to prolonged remission of stage IV breast cancer: a case report.

Tisman G.
Whittier Cancer Research Building, 13025 Bailey Street, Suite A, Whittier, CA 90601, USA. glennmd@gmail.com
Metastatic breast cancer to the liver is considered incurable. Though many patients with liver metastases may enjoy response to chemo-, immuno- and hormonal therapy, those so inflicted rarely remain disease-free from the time of diagnosis for longer than 6-11 months. New laboratory and clinical research identified that cross-talk between activation of the epidermal growth factor family of tyrosine kinase transduction pathways (EGF/HER2) and estrogen receptor (ER) activation plays a role in resistance to hormonal therapy. A 59-year-old woman with a 4.5-cm invasive ductal, ER-positive/PR-negative, grade III adenocarcinoma of the breast was treated with mastectomy. Staging revealed biopsy-proven liver metastases. Surgery was immediately followed with vinorelbine, trastuzumab, tamoxifen and exemestane. The patient underwent a bone scan and PET/CT documented complete remission. She has remained in complete remission for 7 years. It is proposed that a possible mechanism for prolonged remission of stage IV breast cancer in this patient may be related to suppression of EGF/HER2 by trastuzumab, thus inhibiting cross-talk-associated tamoxifen/estrogen withdrawal resistance.

PMID: 20210247 [PubMed - in process]
Quote:
Tamoxifen and exemestane were started after discontinuation of vinorelbine after only 6 weeks of therapy due to a vinorelbine-induced rash. Complete clinical response was confirmed after 2 months from the start of therapy. The patient has remained free of disease for 7 years and receives trastuzumab 6 mg/kg every 6 weeks, tamoxifen 20 mg daily, and exemestane 25 mg daily.
Quote:
The ATAC study reported less than optimal activity for the combination of tamoxifen and anastrozole when compared to the AI alone20. It was decided, however, to continue this patient on the combination of tamoxifen plus AI because of the early success of therapy.
Quote:
It is conjectured that this patient’s prolonged complete remission of 7+ years may represent the result of inhibition of EGFR/HER2-ER cross-talk, thus prolonging benefit from hormonal therapy. However, it is also possible – though less likely – that the independent effects of trastuzumab, tamoxifen and exemestane inhibition of tumor growth is responsible as well.

Maybe the interaction is different between Tam+Anastrazole vs TAM+Exemestane:

Clin Cancer Res. 2005 Dec 15;11(24 Pt 1):8722-7.
Effect of exemestane on tamoxifen pharmacokinetics in postmenopausal women treated for breast cancer.

Hutson PR, Love RR, Havighurst TC, Rogers E, Cleary JF.
School of Pharmacy, University of Wisconsin, Madison, Wisconsin 53705-2222, USA. prhutson@pharmacy.wisc.edu
PURPOSE: Rodent models of human breast cancer suggest that the combination of the steroidal aromatase inhibitor exemestane with tamoxifen may have additive activity. Clinical trials combining tamoxifen with letrozole or anastrazole have shown minor pharmacokinetic drug interactions. We did an open-label crossover clinical trial of the effect of exemestane on tamoxifen pharmacokinetics. DESIGN: Thirty-two postmenopausal women who were clinically disease-free following primary treatments for breast cancer receiving tamoxifen for at least 3 months were studied. Blood was collected for pharmacokinetic analysis after at least 4 months of receiving 20 mg tamoxifen daily. Subjects then began 8 weeks of oral exemestane (25 mg daily), followed by another set of blood samples. RESULTS: There were no serious toxicities noted when the two drugs were combined. There was no significant effect of exemestane on the area under the plasma concentration versus time curve (AUC) of tamoxifen at steady state before [3.04 mg h/L; 90% confidence interval (90% CI), 2.71-3.44] and during exemestane treatment (3.05 mg h/L; 90% CI, 2.72-3.41). There were no significant changes in the formation of primary tamoxifen metabolites. Oral clearance of exemestane averaged 602 L/h based on an average plasma exemestane AUC of 41.5 microg h/L (90% CI, 36.7-62.6). Plasma concentrations of estradiol, estrone, and estrone sulfate decreased when exemestane was begun; estradiol concentrations consistently decreased below the limit of quantitation. CONCLUSIONS: There is no pharmacokinetic interaction between tamoxifen and exemestane. No modification in the standard regimen of either drug seems to be indicated if they are used in combination. The combination of the two drugs was well tolerated during the 8-week evaluation period.

PMID: 16361559 [PubMed - indexed for MEDLINE]

[Jackie07]

Aromasin® is the trade name of Exemestane:

http://www.nlm.nih.gov/medlineplus/d...s/a607006.html

[mmoons]

Pam-

I am sorry you got that news. Please stay stong. Maybe it needs more time. Know that the prayer warriors are lifting you up.

Maureen

[Bill]

Pam, you hang in there. Like Maureen said, maybe it just needs a little more time to work. It sounds like you have a good onc. And I know for sure that you have a good, strong family here sending plenty of prayers and well-wishes your way. Love, Bill

[Ceesun]

Pam, Not sure if this helps, but I am on that combo and my onc gave it almost 4 months before he did scans to look at things...maybe a little more time will work...and perhaps your onc will add to the mix. Hang in there. Ceesun

[Pam P]

Thank you all for your well wishes and encouragement. It keeps me going! Rich - my onc. wanted to use aromasin instead of femara because I'd used femara before and it didn't work for me. So he thought a 'cousin' of it might do better.

[ElaineM]

I am sorry Pam.
I wonder if a chemo can be added to the Herceptin, Tykerb and Aromasin (or Femara)?
Try to stay positive !!

[Rich66]

Ok. Depending on your status, might still be worth considering blocking the estrogen receptor as well as aromatase. I will also throw in my pitch for adding metformin and green tea supplements. If you need to add xeloda, seems worth trying to keep Tykerb and an aromatase inhibitor.

[Pam P]

Rich - The onc. has already said no to the metformin. (of course I could bring it up again in future). Guess I can look for green tea suppl & start them. It sounded like if my onc. adds xeloda he'll drop the tykerb & keep the herceptin with it. Aromasin too I assume if it seems to be helping.

[Mary Anne in TX]

Just want you to know you have my prayers and positive thoughts, Pam. ma

[Shobha]

Dear Pam,

Please know I am praying for you and sending lots of positive thoughts your way!

hugs,
shobha

[Becky]

Dear Pam

I also am thinking about you. See if you can stay on all three targeted therapies (Tykerb, Herceptin, Aromosin) and add the Xeloda too!

[Patb]

Just know you are in my thoughts and prayers and
I hope the combo will work for you.
patb

pam I'm with becky, see how many of those suckers you can block. hang in there sister, we want to see you in Santa Cruz soon!

chrisy

[michka]

Pam I am sorry H and T are not working yet. I agree with Becky , if it doesn't improve and you have to add Xeloda, why abandon Tykerb (if you can sand it)? You are in my thoughts. Hugs. Michka

[Pam P]

Thank you to all of you who hold me up with your encouragement and help.

Chrisy - I hope to be in Santa Cruz later this summer if all goes well. My son is getting married June 26, so no plans will be made until after the wedding is over. But my heart (my butt?) is longing for my favorite rock along the cliff at Pleasure Point.

[Ellie F]

Hi Pam
Sorry that I have no words of wisdom about the combo except that waiting a while longer seems sensible.
Hopefully T-DM1 is around the corner for you girls in the States so this will definitely give you a range of more options.

Love Ellie

[Adriana Mangus]

Tykerb did not do anything for me either.

Why wait? If it does not work, switich to something else.

Ask your onc again. I do not agree with his decision to continue--it seems sensless.

Love,

Adriana