Intraventricular Chemotherapy for Leptomeningeal Carcinomatosis from Lung Cancer: A Feasible and Beneficial Treatment Option?

Abstract

Leptomeningeal carcinomatosis (LMC) is a rare, but rapidly fatal clinical condition. It occurs in approximately 5% to 18% of lung carcinoma cases, 1–3 and tumor-specific occurrence of LMC from lung cancer ranges from 10% to 29%. 4,5 The time from the date of diagnosis of lung cancer to the date of diagnosis of LMC was 2 days to 8 years (median 407 days). 6 In general, LMC occurs in patients with widely disseminated and progressive systemic solid cancer. 2 Novel effective anticancer treatments have improved the survival of patients with advanced non–small-cell lung cancer (NSCLC), which leads to an increasing incidence of LMC. 7 Adenocarcinomas are the most common solid tumors to metastasize to the meninges. 2 Especially in lung cancer, more than 75% of the incidence of LMC is found to be related to an adenocarcinoma histopathology. 1,2,7,8 With the expansion of therapeutic options for systemic treatment of NSCLC, including targeted therapies, the landscape for treating LMC is changing. Data on whether the hydrophilic antifolate pemetrexed is able to pass the blood–brain barrier are limited, 9 although it has demonstrated activity within the central nervous system. 10 Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are able to cross the blood–brain barrier and have shown efficacy in the treatment of brain metastases and LMC. 11–13 Most of the data about the treatment of LMC and its efficacy were collected decades before the approval of pemetrexed, bevacizumab, EGFR TKIs, and anaplastic lymphoma kinase (ALK) inhibitors. Even if intraventricular chemotherapy (IVC) is a preferred treatment for LMC, there are no universally accepted data supporting its effectiveness. Gwak and colleagues, 14 whose report is accompanied by this editorial, investigated IVC in a cohort of 105 NSCLC patients. This is the largest report of NSCLC patients with LMC, who were rather homogenously treated. Every IVC, which consisted of methotrexate as single-agent or in a triple combination with cytarabine and hydrocortisone, was administered by means of an intraventricular reservoir (Ommaya [Baxter; Heyer-Schulte, Deerfield, IL] or Chemoport [Celsite; B. Braun, Boulogne Cedex, France]). Although the authors performed a retrospective study, it is to their credit that some promising data about the efficacy of IVC for NSCLC patients are now available. The investigators did not only calculate survival times, but also applied additional means to determine the response to IVC: they repeated measurements of the intracranial pressure (ICP), they used predetermined criteria for response assessment in cerebrospinal fluid (CSF), and they tentatively evaluated LMC-related symptoms. The authors report that IVC can palliate LMC-associated symptoms. Thirtyfour of 81 patients (42%) with headache and nausea or vomiting at the time LMC was diagnosed, showed an improvement after IVC. Among 54 patients with increased ICP at the entry of the treatment, 20 patients (37%) achieved normal ICP after the IVC.