title: 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.
authors.affiliation: Department of Neuro-Oncology, University of Texas M. D. Anderson Cancer Center, 1400 Holcombe Blvd., Houston, TX 77030, USA. mgroves@mdanderson.org
authors.forename: Morris D
authors.initials: MD
authors.lastname: Groves
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Glantz
authors.forename: Marc C
authors.initials: MC
authors.lastname: Chamberlain
authors.forename: Karen E
authors.initials: KE
authors.lastname: Baumgartner
authors.forename: Charles A
authors.initials: CA
authors.lastname: Conrad
authors.forename: Sigmund
authors.initials: S
authors.lastname: Hsu
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Wefel
authors.forename: Mark R
authors.initials: MR
authors.lastname: Gilbert
authors.forename: Sandra
authors.initials: S
authors.lastname: Ictech
authors.forename: Kathy U
authors.initials: KU
authors.lastname: Hunter
authors.forename: Arthur D
authors.initials: AD
authors.lastname: Forman
authors.forename: Vinay K
authors.initials: VK
authors.lastname: Puduvalli
authors.forename: Howard
authors.initials: H
authors.lastname: Colman
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Hess
authors.forename: W K Alfred
authors.initials: WK
authors.lastname: Yung
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D008875:Middle Aged; D011379:Prognosis; D019772:Topotecan / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D019772:Topotecan