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Herceptin Studies Offer A Mixed Bag
Aside from the issue of congestive heart failure, past studies have suggested a potentially very serious weakness with Herceptin, the problem with central nervous system (CNS) metastasis.
A study from the same Dana Farber Cancer Institute identified CNS metastases in 34% of the women who received Herceptin-based therapy for metastatic breast carcinoma. CNS disease is defined as one or more brain metastases or leptomeningeal carcinomatous (carcinomatous memingitis).
Ironically, that is the same problem they are having with the T-DM1 trial. Brain mets! Some think that patients on the T-DM1 (trastuzumab emtansine) trial should also be given some straight Herceptin, which they think will cross the blood-brain barrier (BBB) and give a certain amount of protection.
The only way for that to happen is a patient may also have to be subjected to an “intrathecal” injection of T-DM1. Herceptin does not cross the BBB because it is a “large” molecule drug. One thing you can definitely say is the T-DM1 is an investigational agent, or just plain experimental.
Dana Farber Cancer Institute identified central nervous system (CNS) metastases in women who receive trastuzumab-based (Herceptin) therapy for metastatic breast carcinoma (Cancer 2003 Jun 15;97(12):2972-7). Central nervous system disease is defined as one or more brain metastases or leptomeningeal carcinomatosis (carcinomatous meningitis). CNS metastases was identified in 34% of patients at a median of sixteen months after diagnosis of metastatic breast cancer and six months from the beginning of Herceptin treatment. Monoclonal antibodies like Herceptin are very large molecules which do not have a convenient way of getting access to the large majority of cells. Plus, there is multicellular resistance, the drugs affecting only the cells on the outside may not kill these cells if they are in contact with cells on the inside, which are protected from the drug. The cell may pass small molecules back and forth.
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