title: Regression of recurrent malignant gliomas with convection-enhanced delivery of topotecan.
abstract: BACKGROUND
  Convection-enhanced delivery of chemotherapeutics for the treatment of malignant glioma is a technique that delivers drugs directly into a tumor and the surrounding interstitium through continuous, low-grade positive-pressure infusion. This allows high local concentrations of drug while overcoming the limitations imposed by toxicity and the blood-brain barrier in systemic therapies that prevent the use of many potentially effective drugs.
  
  
  OBJECTIVE
  To examine the safety profile of a conventional chemotherapeutic agent, topotecan, via convection-enhanced delivery in the treatment of recurrent malignant gliomas and secondarily to assess radiographic response and survival.
  
  
  METHODS
  We performed a prospective, dose-escalation phase Ib study of the topoisomerase-I inhibitor topotecan given by convection-enhanced delivery in patients with recurrent malignant gliomas.
  
  
  RESULTS
  Significant antitumor activity as described by radiographic changes and prolonged overall survival with minimal drug-associated toxicity was demonstrated. A maximum tolerated dose was established for future phase II studies.
  
  
  CONCLUSIONS
  Topotecan by convection-enhanced delivery has significant antitumor activity at concentrations that are nontoxic to normal brain. The potential for use of this therapy as a generally effective treatment option for malignant gliomas will be tested in subsequent phase II and III trials.
authors.affiliation: Department of Neurological Surgery, Columbia University Medical Center, New York, New York 10032, USA. jnb2@columbia.edu
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Bruce
authors.forename: Robert L
authors.initials: RL
authors.lastname: Fine
authors.forename: Peter
authors.initials: P
authors.lastname: Canoll
authors.forename: Jonathan
authors.initials: J
authors.lastname: Yun
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Kennedy
authors.forename: Steven S
authors.initials: SS
authors.lastname: Rosenfeld
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Sands
authors.forename: Krishna
authors.initials: K
authors.lastname: Surapaneni
authors.forename: Rose
authors.initials: R
authors.lastname: Lai
authors.forename: Candix L
authors.initials: CL
authors.lastname: Yanes
authors.forename: Emilia
authors.initials: E
authors.lastname: Bagiella
authors.forename: Robert L
authors.initials: RL
authors.lastname: DeLaPaz
mesh_terms: D000328:Adult; D000368:Aged; D001288:Attention / Q000187:drug effects; D018481:Convection; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000187:drug effects; D008875:Middle Aged; D009460:Neurologic Examination; D009483:Neuropsychological Tests; D011446:Prospective Studies; D011788:Quality of Life; D011930:Reaction Time / Q000187:drug effects; D015173:Supratentorial Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D011795:Surveys and Questionnaires; D014057:Tomography, X-Ray Computed; D059004:Topoisomerase I Inhibitors / Q000008:administration & dosage*; D019772:Topotecan / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D059004:Topoisomerase I Inhibitors; D019772:Topotecan