A multicenter phase II trial of intrathecal topotecan in patients with meningeal malignancies

Abstract

To determine the therapeutic efficacy (13-week and 26-week CNS progression-free survival [PFS], response rate, and overall survival) and safety of intraventricular (IVent) topotecan in patients with neoplastic meningitis (NM), we conducted a phase II, open-label, nonrandomized, single-arm trial of IVent topotecan in patients with NM using 400 mug of topotecan IVent twice weekly for 6 weeks, followed by evaluation with imaging, cerebrospinal fluid (CSF), and physical examinations. In the absence of disease progression, patients were then treated with IVent topotecan weekly for 6 weeks, twice monthly for 4 months, and monthly thereafter. Sixty-two patients (23 males and 39 females) were enrolled from April 2001 through March 2006. Median age and KPS at enrollment were 56 (range 5-83) and 80 (range 60-100), respectively. Primary cancers included breast (19), lung (13), CNS (14), and others (16). Forty patients (65%) completed the 6-week induction period, among whom 13 (21%) had CSF clearance of malignant cells. Kaplan-Meier estimates of PFS at 13 and 26 weeks were 30% (95% confidence interval [CI], 20%-45%) and 19% (95% CI, 11%-34%). Overall median survival (50 deaths) was 15 weeks (95% CI, 13-24 weeks). The most common side effect was chemical meningitis in 32% of patients (5% grade 3); 32% experienced no drug side effects. IVent topotecan is well tolerated, but provides no added benefit over other IVent therapies. Because of its modest side effect profile, combining IVent topotecan with other IVent or systemic interventions should be considered.

Concurrent radiotherapy and intrathecal methotrexate for treating leptomeningeal metastasis from solid tumors with adverse prognostic factors: A prospective and single‐arm study

“…To our knowledge, lots of previous studies enrolled patients with various solid tumors2, 17, 24, 29, 30, 31, 32 despite the prognosis of LM from breast cancer was satisfactory 33. Therefore, patients with different primaries were enrolled in this study.…”

Molecular Profiling of Tumor Cells in Cerebrospinal Fluid and Matched Primary Tumors from Metastatic Breast Cancer Patients with Leptomeningeal Carcinomatosis

“…Leptomeningeal carcinomatosis, in which tumor cells metastasize to the leptomeninges and cerebrospinal fluid (CSF), is a particularly virulent syndrome with extremely high morbidity and mortality (1)(2)(3)(4)(5). Furthermore, central nervous system (CNS) involvement in breast cancer, including leptomeningeal carcinomatosis, seems to be increasing due to longer survival times and more efficacious treatment against other sites of systemic disease (6).…”

Intracerebroventricular drug administration

“…[63] However, in a report in which 17 patients with central nervous system embryonal tumors were treated with liposomal ARA-C, these symptoms were minimized by administering prophylactic dexamethazone. [64] Leukoencephalopathy is a particularly serious complication of ICV therapy.…”