Intrathecal trastuzumab (Herceptin) and methotrexate for meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer: a case report

Abstract

Leptomeningeal carcinomatosis represents a rare manifestation of metastatic breast cancer (MBC). We herewith report on a patient suffering from HER2 overexpressing MBC who received intrathecal methotrexate and trastuzumab for meningeal carcinomatosis. A 48-year-old woman was diagnosed with breast cancer in December 2002. Following surgery, six cycles of adjuvant FE100C plus irradiation and, subsequently for 1 year, trastuzumab were given. As a result of disseminated metastatic spread in October 2005, the patient received whole-brain radiotherapy for symptomatic central nervous system involvement, and was put on several trastuzumab-based combination regimens (capecitabine, vinorelbine, paclitaxel). In June 2006, the patient developed clinical signs of terminal cone involvement with overflow incontinence and paraparesis of the legs. Immediate radiation led to partial relief from clinical symptoms. Subsequently, the patient was put on the tyrosine kinase inhibitor lapatinib and capecitabine (August to October 2007), but on November 6th the patient suffered again from overflow incontinence and weakness of the legs. Failing to respond to lapatinib, the patient received gemcitabine/cisplatin and, additionally, was recommenced on intravenous trastuzumab. Owing to progressive leptomeningeal disease, the patient received repeated doses of intrathecal methotrexate and trastuzumab. Within 2 weeks and four intrathecal treatments, cerebrospinal fluid cytology showed the absence of tumor cells. Moreover, a striking clinical improvement with resolution of the paraparesis of the legs and overflow incontinence was observed. This case report gives details regarding the clinical course of a breast cancer patient who received intrathecal trastuzumab and methotrexate via lumbar puncture for meningeal carcinomatosis of HER2-overexpressing MBC.

Role of Intrathecal Rituximab and Trastuzumab in the Management of Leptomeningeal Carcinomatosis

“…[12][13][14][15][16][17] Interestingly, the patient who died at day 39 of intrathecal trastuzumab treatment died due to progression of visceral metastases and was considered to be in remission with regard to the leptomeningeal carcinomatosis. 10 Tumor cell counts were also found to be eliminated or substantially decreased in 4 of 5 patients. 10,13,14,17 In 2 reports, response appeared to be related to dose.…”

“…10 Tumor cell counts were also found to be eliminated or substantially decreased in 4 of 5 patients. 10,13,14,17 In 2 reports, response appeared to be related to dose. 14,15 In 1 of these, the patient was started on 20 mg weekly and benefits from intrathecal trastuzumab were not appreciated until doses were increased past 30 mg.…”

“…Doses of trastuzumab ranged from 5 to 100 mg and were repeated after as little as 3 days in 1 report to as long as 3 weeks in others. 10,[12][13][14] The most common schedule was 20-30 mg weekly. All doses, including doses up to 100 mg, and schedules were well tolerated.…”

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

“…No clear clinical benefit could be documented, but there were no side effects other than mild local ventricle inflammation at autopsy [10]. This led others to administer IT trastuzumab [11][12][13][14][15][16][17]. Most patients experienced symptoms improvement and no adverse neurological effects.…”

“…No consensus exists on the adequate dosing and frequency of IT trastuzumab, ranging from 5mg [10,17] to 100mg [14] dosing in a weekly [10,[13][14][15][16][17] to every three weeks [11,13] schedule, with 25mg…”