steroid pretreatment used with taxanes found to interfere with herceptin's effective

[Lani]

ness
TAKE A DEEP BREATH AND CONSIDER--
1) IT IS BASED ON WORK IN A PETRI DISH, NOT IN A LIVE HUMAN SO IT IS NOT CERTAIN THE RESULT WOULD BE THE SAME IN A WHOLE HUMAN BEING

HOWEVER, THE TUMOR CELL LINE THEY LOOKED AT WAS A HER2+ER+ CELL LINE (THEY DID NOT LOOK AT SKBR3, A HER2+ER- CELL LINE)

THE FACT IS THAT THE HERCEPTIN ADJUVANT STUDIES SHOWED SUCH WONDERFUL RESULTS WHEN COMPARED TO THE OTHER ARM WHICH WAS
A TAXANE WITHOUT HERCEPTIN, BUT STILL WITH STEROID PRETREATMENT

SO THE IMPROVEMENTS IN DFS AND OS ARE STILL VALID, BUT THERE IS A CHANCE THE ABSOLUTELY IMPROVEMENTS MIGHT HAVE BEEN EVEN GREATER IF THEY WERE ABLE TO GIVE HERCEPTIN WITH A CHEMODRUG WHICH DID NOT REQUIRE STEROID PRETREATMENT (and noone knows the results of herceptin monotherapy)

Just food for thought--not to alarm anyone

The adventure is continuing and those who have had herceptin as part of their treatment until know remain "pioneers"

There is still much to learn!

1: Int J Oncol. 2008 Mar;32(3):683-8.
Dexamethasone interferes with trastuzumab-induced cell growth inhibition through restoration of AKT activity in BT-474 breast cancer cells.

Sumikawa T, Shigeoka Y, Igishi T, Suyama H, Yamasaki A, Hashimoto K, Matsumoto S, Takeda K, Ueda Y, Shimizu E.
Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan.
The combination of trastuzumab with paclitaxel (PTX) is an important option for the treatment of HER2-positive breast cancer. Dexamethasone (Dex) premedication is routinely used in the treatment with PTX. The interactions among Dex, PTX and trastuzumab were evaluated in BT-474 cells. Dex interfered with trastuzumab-induced cell growth inhibition without clear effects on PTX-induced cytotoxicity. Trastuzumab dephosphorylated retinoblastoma protein (pRB). Dex restored this trastuzumab-induced dephosphorylation of pRB and released trastuzumab-induced G1 arrest. Trastuzumab suppressed AKT activity without affecting ERK activity. A specific inhibitor for the phosphatidylinositol 3-kinase/AKT pathway, LY294002, inhibited cell growth and AKT and pRB phosphorylation. Dex restored the trastuzumab-induced suppression of AKT without affecting ERK activity. It was concluded that Dex interferes with trastuzumab-induced cell growth inhibition, at least partially, through the restoration of trastuzumab-induced AKT suppression and subsequent pRB dephosphorylation in BT-474 breast cancer cells. These observations support the development of new chemotherapeutic regimens without glucocorticoid premedication.
PMID: 18292946 [PubMed - in process]

[hutchibk]

Sounds like a good reason to look further toward the use of Abraxane in combo with Herceptin... no?