Herceptin is now being tried intrathecally (injected into the brain via the CSF)

[Lani]

I posted this to the wrong forum--there is no clinical trial--yet.
Herceptin is now being tried intrathecally (injected into the brain via the CSF)
--CSF is the cerebral spinal fluid that bathes the brain and circulates around the parts of the brain and spinal cord

--carcinomatosis just means "widespread cancer"

leptomeningeal or meningeal involvement is different than parenchymal involvement as I explained in an earlier post (parenchymal means within the tissue of the brain itself rather than on its outside linings/covers)

Here is the abstract:

Oncol Rep. 2006 May;15(5):1373-7. Links

Application of intrathecal trastuzumab (Herceptintrade mark) for treatment of meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer.

Stemmler HJ, Schmitt M, Harbeck N, Willems A, Bernhard H, Lassig D, Schoenberg S, Heinemann V.

Department of Internal Medicine III, University of Munich - Klinikum Grosshadern, D-81377 Munich, Germany. joachim.stemmler@med.uni-muenchen.de.

Leptomeningeal carcinomatosis represents a rare manifestation of metastatic breast cancer (MBC). A 39-year-old female presenting with HER2-overexpressing MBC and suffering from meningeal carcinomatosis was treated with the humanized antibody trastuzumab directed to HER2 by intrathecal administration. The patient was diagnosed with HER2-overexpressing stage III breast cancer in December 2003. In August 2004, the patient developed a singular intracerebral metastasis which was resected by neurosurgery followed by whole-brain radiotherapy. Since MRI and cerebrospinal fluid (CSF) analyses indicated meningeal carcinomatosis, the patient was commenced on trastuzumab (6 mg/kg q3w) and capecitabine (2.500 mg/m(2) d1-14, q3w). Prompted by clinical deterioration, 5 repeated doses of intrathecal methotrexate (15 mg/dose) were administered, yet without clinical improvement. There is initial evidence that trastuzumab does not reach an adequate concentration in CSF after intravenous application. Nevertheless, infiltration of trastuzumab into CSF is facilitated under conditions of an impaired blood-brain barrier, as it is known for meningeal carcinomatosis. For patients with leptomeningeal disease, intrathecal application of trastuzumab may provide an interesting therapeutical approach for patients with HER2 overexpressing metastatic breast cancer. Therefore, an Ommaya reservoir for intrathecal treatment with trastuzumab was placed surgically and intrathecal therapy was begun with escalating doses of trastuzumab (5-20 mg), which proved to be effective and well tolerated by the patient. Within 2 weeks after treatment, the patients' condition improved significantly and cell counts in CSF obtained from the Ommaya reservoir remained low for 11 months after first diagnosis of meningeal carcinomatosis when clinical symptoms and MRI indicated progression of meningeal and cerebral disease.

PMID: 16596213 [PubMed - in process]

[Lani]

and found this article about experimental work in mice similar to the article above. In mice it had to be injected locally, not in the lumbar (back) region:
Clinical Cancer Research Vol. 7, 2050-2056, July 2001
© 2001 American Association for Cancer Research
Regular Articles

Treatment of Meningeal Breast Cancer Xenografts in the Rat Using an Anti-P185/HER2 Antibody1

Ira Bergman2, Mamdouha A. Barmada, Judith A. Griffin and Dennis J. Slamon
Departments of Pediatrics [I. B., J. A. G.], Neurology [I. B.], and Pathology [M. A. B.] University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213; and Division of Hematology and Oncology, UCLA School of Medicine, Los Angeles, California 90024 [D. J. S.]

The metastatic spread of breast cancer to the leptomeninges (LM) is a painful, debilitating, and usually lethal condition. Current therapies are generally ineffective or extremely toxic. The current study evaluated monoclonal antibody therapy in an animal model of LM human breast cancer. Monoclonal antibody 4D5, which recognizes the extracellular domain of the HER2/neu receptor, was administered into the cerebrospinal fluid of athymic rats implanted with human breast cancer cell lines. Continuous intraventricular administration of 4D5 inhibited growth of SKBR3 cells that overexpress HER2/neu but not of MCF7 cells, which do not. Inhibition was dose-dependent, with higher doses of 4D5 producing an improved response. i.p. administration of cisplatin in addition to 4D5 did not improve results. Continuous administration of 4D5 into the lumbar, as opposed to the ventricular intrathecal space, was not therapeutically effective. Treatment with 4D5 did not result in outgrowth of cells lacking expression of the HER2/neu receptor. These results suggest that 4D5, administered regionally, may palliate LM metastases from HER2/neu-overexpressing breast carcinoma.

[R.B.]

As ususal amazed by the depth of your reading.

RB