[YoungMD]

I wanted to add also this. In LM patients, CSF flow abnormalities are common. Circulating cancer cells/emboli obstruct the drainage of the meninges and hydrocephalus can develop, with all of its associated clinical manifestations. Although as the CSF clears of cytologically perceptible tumor cells, one would expect that the hydrocephalus subsides or normalizes. During this time, then, extraction of CSF via the Ommaya reservoir should be undertaken, as much as 35 ml per IT administration, until there is MRI confirmed resolution of the hydrocephalus.

If possible, a CSF flow obstruction study should be conducted to make sure that the neuroaxis is accessible to IT administered agents. If there is a tumor blocking CSF flow, say in the lumbar spine, the area below will develop multiple metastasis since it is not being treated, unless systemic therapy is penetrating the BBB in the obstructed area. Such a study, radionuclide ventriculography, also helps to identify gross masses requiring radiotherapy. IT Herceptin or any other cytotoxic agent has limited effect on gross masses, and spot radiation should be applied to the known tumors.

Finally, salvage therapy. What happens when methothrexate stops working? Or Herceptin? Thiotepa is seen as a salvage therapy for when methotrexate fails, but can also be used as a first line therapy, as is done in Yale. In the case of Herceptin, that is more frightening since it may suggest that the tumor underwent clonal selection to lose its HER2 ligand. Tykerb was suggested as a second line salvage therapy in cases of suspected desensitization to Herceptin, combined with Xeloda - the issue, however, being that you need high doses of Tykerb to push a therapeutic dosage into the brain from the bloodstream. I've read a case report in which etoposide 1 mg/wk was used as salvage therapy in the case of methothrexate failure. From what I read in this thread, some MO's may also seek to up the dosage of IT Herceptin to 150 mg or 200 mg/wk, suggesting that the tumor in such cases has simply been downregulated and did not in fact lose the HER2 ligand. A combination of IT Herceptin and Perjeta is also something I think would improve outcomes in the case of IT Herceptin monotherapy failure, but that is just my opinion. For the sake of my Mother, I want to see who would do such a protocol of treatment. Are there others? I've seen IT interferon as a third line therapy in an article, but that is its own can of worms and has probably only limited effect.