Complete response in HER2+ leptomeningeal carcinomatosis from breast cancer with intrathecal trastuzumab

Abstract

Trastuzumab, a monoclonal antibody against the HER2 receptor, is a major breakthrough in the treatment of HER2+ breast cancer. However, its high molecular weight precludes it from crossing the intact blood-brain barrier, making the central nervous system a sanctuary to HER2+ breast cancer metastases. We prospectively assessed functional outcome and toxicity of administering trastuzumab directly into the cerebrospinal fluid of a patient with leptomeningeal carcinomatosis and brain metastases from HER2+ breast cancer that had already been treated with other intrathecal chemotherapy, with no benefit. Upon signed informed consent, weekly lumbar puncture with administration of trastuzumab 25mg was begun to a 44 year-old women with metastatic breast cancer (lymph node, bone, lung and liver involvement) previously treated with tamoxifen, letrozole, anthracyclines, taxanes, capecitabine, intravenous trastuzumab and lapatinib. She received 67 weekly administrations of intrathecal trastuzumab with marked clinical improvement and no adverse events. She survived 27 months after leptomeningeal carcinomatosis diagnosis.A complete leptomeningeal response, with no evidence of leptomeningeal metastasis at necropsy, was achieved. We believe that intrathecal trastuzumab administration should be prospectively evaluated to confirm clinical activity and optimize dose, schedule and duration of treatment.

Advancements in diagnosis and treatment of meningeal carcinomatosis in solid cancer

“…[53] Additionally, trastuzumab and topotecan has recently been used in intrathecal chemotherapy in MC from breast cancer. [54][55][56] Topotecan, an alkylating agent, showed variable effects. [57] A retrospective review of 149 patients with breast cancer-related MC showed that there was no significant difference in overall survival between patients treated with intra-CSF liposomal cytarabine and methotrexate, with the median overall survival of 4.2 months.…”

“…[81,82] A patient with MC received 67 cycles of weekly 25 mg IT trastuzumab with a long survival time (27 months) after MC diagnosis and dramatic clinical improvement. [54] Moreover, intra-CSF trastuzumab combined with intra-CSF MTX and ara-C has been performed in two patients with MC. The survival time of the two patients was 13.5 months and 6 months respectively with a clinical benefit and without substantial toxicity.…”

Emlőtumor intracranialis metasztázisainak eredményes szisztémás palliatív kemoterápiája

“…A HER-2-pozitív emlődaganatos betegeknél a zsigeri metasztázisok kezelésében alkalmazott trastuzumab, pertuzumab és TDM-1 is képes az agyi áttétek progresszióját lassítani, illetve a teljes túlélést növelni [8][9][10], bár ebben az indikációban alkalmazásukra egyértelmű ajánlás még nem született. Meningitis carcinomatosa esetén intrathecalis trastuzumabkezelés mellett elért komplett klinikai remisszióról is szól esettanulmány [11].…”

Immunohistochemical expression of erbb2 in adamantinomatous craniopharyngiomas: a possible target for immunotherapy

“…However, trastuzumab has also been demonstrated to be effective when used as single agent in the treatment of metastatic ErbB2-positive breast cancer (29). Although trastuzumab does not cross the blood-brain barrier due to its large molecule size, its administration via the intrathecal route has been reported to be effective for brain metastasis of ErbB2 positive breast cancer (24). In recent years, research efforts have focused on improving the delivery of trastuzumab to the Our study results were consistent with all of these studies and indicated nuclear accumulation of β-catenin in all of the ACP tissue specimens, predominantly accumulated in epithelial cells within the whorl-like arrays (7,8).…”