{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T18:47:25Z","timestamp":1783190845374,"version":"3.54.6"},"reference-count":50,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Oncol Pharm Pract"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To review the safety and tolerability of intrathecal (IT) chemotherapy used in the treatment of leptomeningeal disease (LMD) from solid and hematologic malignancies, with emphasis on agent-specific toxicity profiles and delivery-associated adverse effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data Sources<\/jats:title>\n                    <jats:p>This review synthesizes data from prospective and retrospective clinical studies and pharmacokinetic analyses evaluating IT chemotherapeutic agents for LMD. Agents reviewed include methotrexate, cytarabine, pemetrexed, topotecan, etoposide, thiotepa, trastuzumab, and intrathecal immune checkpoint inhibitors. Systemic pharmacokinetic and toxicity data were reviewed to contextualize adverse effects of IT chemotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data Summary<\/jats:title>\n                    <jats:p>Intrathecal chemotherapy was generally associated with predominantly low-grade toxicities. Common adverse events included headache, nausea, vomiting, meningismus, fatigue, and radicular or myelopathic symptoms. Methotrexate and cytarabine were the most frequently utilized IT agents and demonstrated higher risks of neurotoxicity, including chemical arachnoiditis, encephalopathy, and leukoencephalopathy, particularly with cumulative dosing and concurrent radiotherapy. Pemetrexed and topotecan demonstrated favorable tolerability across multiple studies, with infrequent grade \u22653 toxicities. Targeted IT therapies, including trastuzumab and immune checkpoint inhibitors, were associated primarily with mild and self-limited adverse events in early studies. Delivery-related toxicities were generally manageable, with Ommaya reservoir administration associated with improved drug distribution and treatment feasibility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Intrathecal chemotherapy for LMD is generally safe and well tolerated, however, methotrexate and cytarabine are associated with higher neurotoxicity risk. Newer intrathecal agents demonstrate favorable safety profiles and may represent tolerable treatment options for select patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10781552261422155","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T14:53:42Z","timestamp":1771340022000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Adverse effects associated with intrathecal chemotherapy for leptomeningeal disease"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1857-3271","authenticated-orcid":false,"given":"Lauren","family":"Martin","sequence":"first","affiliation":[{"name":"Medical College of Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Campbell","family":"Scott","sequence":"additional","affiliation":[{"name":"WellStar Health System"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"IV","given":"Gerald C","family":"Wallace","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology &amp; Neurology, WellStar Health System, Medical College of Georgia and the Georgia Cancer Center, Augusta, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"key":"e_1_3_2_2_2","article-title":"Carcinomatous meningitis: leptomeningeal metastases in solid tumors","volume":"4","author":"Le Rhun E","year":"2013","unstructured":"Le Rhun E, Taillibert S, Chamberlain MC. 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