Meningeal Carcinomatosis From Breast Carcinoma Responsive to Trastuzumab

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.13.3297 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11432901 Meningeal Carcinomatosis From Breast Carcinoma Responsive to Trastuzumab Randi H. BaculixRandi H. BaculiSearch for articles by this author , Samer SukixSamer SukiSearch for articles by this author , John NisbettxJohn NisbettSearch for articles by this author , Norman LeedsxNorman LeedsSearch for articles by this author , Morris GrovesxMorris GrovesSearch for articles by this author Bernhard C. PestalozzixBernhard C. PestalozziSearch for articles by this author Show More The University of Texas M.D. Anderson Cancer Center, Houston Cancer Clinics, Houston, TXUniversity Hospital, Zurich, Switzerland https://doi.org/10.1200/JCO.2001.19.13.3297 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse01072001In Reply:Baculi et al describe a case of meningeal carcinomatosis (MC) owing to metastatic breast cancer treated with radiotherapy to the lumbosacral spine and with intravenous trastuzumab. Interestingly, this patient had previously received the combination of docetaxel with an anthracycline, which has been shown to be associated with a high incidence (30%) of CNS metastases.1 Given the "marked abatement in the leptomeningeal deposits in the posterior fossa and in the thoracic and lumbar regions," the authors claim that this case "demonstrates a response of MC to intravenous trastuzumab." This statement deserves some comment. First, response criteria in leptomeningeal metastasis are not standardized. Most studies define complete response as the normalization of CSF and improvement of clinical symptoms. In this case there was no clinical improvement: the patient remained paraplegic with a lack of bowel and bladder control. Although later in the course intrathecal cytarabine was given, the authors do not report on CSF findings at that time. Were there still malignant cells? At what cell count? Second, the radiologic response to single-agent intravenous trastuzumab was found after only 3 weekly treatments, which is much earlier than the usual 8 to 12 weeks used for reassessment in trastuzumab trials.2 At that time intrathecal cytarabine was added and (presumably) intravenous trastuzumab was continued. Progression of MC was noted 6 weeks later. Therefore, this response to trastuzumab was a very transient improvement limited to radiologic findings. Third, although not mentioned by the authors, it is likely that this patient was given corticosteroids after the diagnosis of MC. Could they have contributed to the radiologic improvement?It is well known that the intact blood-brain barrier limits CNS penetration to molecules with molecular weights up to 200 da. Nevertheless, some cytotoxic agents of larger size have shown efficacy against CNS tumors, presumably because the latter disrupt the blood-brain barrier. In conclusion, it is not impossible that large molecules like trastuzumab (molecular weight: 145,000 da) might have efficacy in CNS metastases, although this has not been demonstrated very convincingly in this case. 1. Crivellari D, Pagani O, Veronesi A, et al: High incidence of central nervous system involvement in patients with metastatic or locally advanced breast cancer treated with epirubicin and docetaxel. Ann Oncol 12:: 353,2001-356, Crossref, Medline, Google Scholar2. Slamon D, Leyland-Jones B, Shak S, et al: Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:: 783,2001-792, Crossref, Medline, Google Scholar