362 Y. H. Chen et al./JCOS 25(2009) 357-364of CSF CA153 has not allowed an estimation oftreatment efficacy [16], and no definite laboratory datacan exhibit the efficacy of intrathecal trastuzumabexcept cytology.Monitoring of trastuzumab CSF levels was notavailable in our study, and we were not able to confirmthe trastuzumab concentration in the CSF. Butobvious association between intrathecal administrationof trastuzumab and CSF levels of trastuzumabwas observed [17]. Besides, less association of trastuzumabconcentration in serum and CSF was also reported,even after WBRT [17]. Although intravenoustrastuzumab with or without capecitabine revealed theefficacy <strong>for</strong> leptomeningeal carcinomatosis [14,26],no definite mechanism was reported. Because we hadtapered steroid dose during the first month, we considersteroid less likely contributed to the prolongedclinical improvement observed in this case.As demonstrated in Table 1, intrathecal trastuzmabwith total dose 20~40 mg per week was everreported [16-19,21]. To our knowledge, no immediateside effect of intrathecal trastuzumab has been reported,and there is no evidence of local inflammationor other drug toxicity at autopsy [18]. However, dataon the activity and safety of higher-dose intrathecaltrastuzumab needs more studies and only Mir et al.reported trastuzumab 100 mg weekly four cycles wasgiven <strong>for</strong> leptomeningeal carcinomatosis [20]. In ourcase report, fifteen cycles of high-dose (80~100 mgweekly) trastuzumab were given <strong>for</strong> meningeal carcinomatosiswithout obvious side effect. Our experiencesuggests that it is safe to use high-dose (80~100 mgper week) intrathecal trastuzumab <strong>for</strong> meningeal carcinomatosis.Also, long-term (46 injections, 75 weeks)intrathecal trastuzumab without obvious side effectwas noted. In our case, trastuzumab was reconstitutedwith sterile water, resulting in a solution to avoidpotential neurotoxicity. General bacteriostatic watercontains 1.1% benzyl alcohol, and the risks of anaphylaxisand neurotoxicity from the preservative agenthave been reported [32]. Mir et al. reported admini-stration of intrathecal trastuzumab by lumbar puncture[20] instead of using an Ommaya reservoir [16-19,21],and data comparing lumbar puncture versus Ommayareservoir in breast cancer-related meningeal carcinomatosisis not available to date.In our case, the activity of intrathecal trastuzumabwas confirmed by persistence of negative CSF cytology<strong>for</strong> at least five months. Similar cytology finding[16,17,19,21] and partial response of MRI [21] havebeen reported, revealing the efficacy of intrathecaltrastuzumab <strong>for</strong> meningeal carcinomatosis. In our case,neurological symptoms exacerbated under intrathecaltrastuzumab 20 mg weekly and improved under modificationto higher dose (80~100 mg weekly). Onepossible explanation is higher-dose trastuzumab overcameresistance, but definite data on the associationbetween dose and efficacy was limited.As demonstrated in Table 2, survival in our casesince the use of intrathecal trastuzumab was sixmonths, and the average survival was nine months(range