Any info on HKI-272?
 

Hi,

Anyone familiar with HKI-272 which is currently in Phase II trial? This is one of the options that was presented to my sister (stage iv) after she recently progressed on tykerb/herceptin after 4 months of stability. She has done great on it in terms of feeling good so the alternative of another bio treatment vs chemotherapy is a positive for this option. She has not done so well with side effects on prior chemo regimines.

Excerpt from http://pubs.acs.org/cen/coverstory/84/8432cancer.html

As with Tykerb, studies of HKI-272 to date have been conducted with HER2-positive patients who have been previously treated with Herceptin. Early-phase trials have been promising. Of 23 evaluable patients in a Phase I trial to treat breast cancer, seven had confirmed partial responses, "a high rate when you consider all of these patients had multiple prior rounds of therapy, including Herceptin," Rabindran notes.
On the basis of those results, Wyeth launched Phase II trials of HKI-272 to treat metastatic breast cancer in December. The firm has yet to determine a timeline for their completion and the subsequent initiation of Phase III studies.

Hki-272
 

Hi, did your sister start the HKI-272? I have a friend who has been on it 4.5 months. She has extensive mets and seems to be responding to this drug quite well. I also aim to try it once the Seattle study site opens.

Thanks,
Theresa

Hki-272
 

HKI-272 was suggested as a possible next step when/If my mom's cancer became resisant to Herceptin when we visited Dana Farber 2 weeks ago. I researchedit when we got back.

Here is some info from a paper:

Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase.

Rabindran SK, Discafani CM, Rosfjord EC, Baxter M, Floyd MB, Golas J, Hallett WA, Johnson BD, Nilakantan R, Overbeek E, Reich MF, Shen R, Shi X, Tsou HR, Wang YF, Wissner A.

Department of Oncology, Wyeth Research, Pearl River, New York, USA. Rabinds@wyeth.com

HER-2 belongs to the ErbB family of receptor tyrosine kinases, which has been implicated in a variety of cancers. Overexpression of HER-2 is seen in 25-30% of breast cancer patients and predicts a poor outcome in patients with primary disease. Trastuzumab (Herceptin), a monoclonal antibody to HER-2, is specifically approved for HER-2-positive breast cancer but is active only in a subset of these tumors. Blocking HER-2 function by a small molecule kinase inhibitor, therefore, represents an attractive alternate strategy to inhibit the growth of HER-2-positive tumors. HKI-272 is a potent inhibitor of HER-2 and is highly active against HER-2-overexpressing human breast cancer cell lines in vitro. It also inhibits the epidermal growth factor receptor (EGFR) kinase and the proliferation of EGFR-dependent cells. HKI-272 reduces HER-2 receptor autophosphorylation in cells at doses consistent with inhibition of cell proliferation and functions as an irreversible binding inhibitor, most likely by targeting a cysteine residue in the ATP-binding pocket of the receptor. In agreement with the predicted effects of HER-2 inactivation, HKI-272 treatment of cells results in inhibition of downstream signal transduction events and cell cycle regulatory pathways. This leads to arrest at the G(1)-S (Gap 1/DNA synthesis)-phase transition of the cell division cycle, ultimately resulting in decreased cell proliferation. In vivo, HKI-272 is active in HER-2- and EGFR-dependent tumor xenograft models when dosed orally on a once daily schedule. On the basis of its favorable preclinical pharmacological profile, HKI-272 has been selected as a candidate for additional development as an antitumor agent in breast and other HER-2-dependent cancers.

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There is a climical trial at Dana Farber at this link as well:

http://www.dana-farber.org/res/clinical/trials/adult/default.html?n-state=http://www.emergingmed.com/pub_search_trial_detail.asp?i_trial_sys_id%3d22032 %26i_site_sys_id%3d0~~~G!0A1237295D04!LYOMwg4%252b 3NNzpuUVR3A%3d~emed-trials~~~@http://syndicator.www.emergingmed.com/dfci/my-emergingmed-trials-7

Hope this helps.

Hki-272
 

I am newly diagnosed and have had no prior treatment at all but they want to start me out in this trial. Is this a last resort? Everyone else seems to have other treatments and now I am so confused.

Hki-272
 

Hi Joanne

I dont know where you are located or your specific situation but I think it will help if you get a second opinion. I am really worried that they are offering this to you as a first line of treatment. I wonder what in your specific case prompted them to do this.

Dana Farber in Boston is setup to provide second opinions. Please go to their website and DFCI.org and you can see the process laid out. I suggest you atleast get a second opinion if possible by phone from Dr. Karen Anderson at Dana Farber. Her number is 617-632-3495. Best of luck

I have started HKI-272 trial..
 

Hello all, just to let you know I began the Wyeth Phase-II trial of HKI-272 one week ago. I will keep all posted as to results. I have mets in both lungs, extensively in lymph system, in abdomen and on skin. Never responded to anything for even a brief period, with the one exception of lapatinib/xeloda to which i responded for exactly 5 weeks.

Keep your fingers crossed!

Theresa

HKI-272 was a bust for me
 

Hi all, just to update you: I did exactly one month on Wyeth's tyrosine kinase inhibitor HKI-272 in a phase II trial at Seattle. It did not work on me, my lung mets progressed massively in that time and I'm now on oxygen, contemplating Hospice vs one last-ditch effort a chemo, which never helped me before.

Just wanted others contemplating this drug to know of my experience,

Theresa

Update
 

Hi,

I thought I would update you all on my sister's progress. She did go on the HKI trial and did OK on it for ~4 months. There was some slight progression in her latest scans so it is time to look for something new now.

Of course, we would have liked this treatement to work much longer, but the side effects of this drug were minimal. My sense is that her prior treatment (combination of tykerb/herceptin) was more effective for her even though she was on that trial for about the same amount of time.

Jo-Ann, I would seek out another opinion if they are considering starting you out on this drug and you are newly diagnosed. This drug does hold some promise, but it is in the early trial stages. There are many treatments out there to consider with a history of success behind them.

MaggieD

HKI-272 is almost exactly the same as Tykerb, another Tyrosine Kinase Inhibitor. There is some minute difference as per my Onc. So chances are if you fail on HKI, you won't do any better with Tykerb or BIBW-1229 or many of the other Tyrosine Kinase Inhibs now in studies. My friend is on HKI and doing really well, except for Diarhea and rashes, her skin mets and lymph are clearing up. She has been flying to Denver for treatments for 2 months now. Good luck and I hope this works for you. Love, Vickie

I went on the HKI-272 trial in January 2007 for positive nodes in supraclavicular area. The nodes were noticeably smaller by touch within 1 week of starting the drug. I went for 5 months before nodes started to swell again and last petscan showed positive nodes in supraclav again and very small positive node in chest wall near my windpipe. Diarrhea and splitting of fingertips and toes are the only side effects I've had with the HKI but it's been quite manageable. My Onc has also told me that HKI is very similiar to Tykerb(lapatinib) but that Tykerb in combo with chemo drug capecitabine might be the next step for me.