title: Salvage chemotherapy with CPT-11 for recurrent meningioma.
abstract: BACKGROUND
  A prospective Phase II study of irinotecan (CPT-11) in adult patients with recurrent surgery and radiotherapy-refractory WHO Grade I meningioma.
  
  
  METHODS
  Sixteen patients (5 men; 11 women) ages 48-70 years (median 62.5), with recurrent meningioma were treated. All patients had previously been treated with surgery (complete in 4; partial in 9; biopsy in 3) and involved-field radiotherapy (median dose 54 Gy; 12 following first surgery and 4 following second surgery). Additionally, eight patients underwent re-operation (complete in 2; partial in 6) and eight patients were treated with salvage stereotactic radiosurgery. No patient was treated with prior chemotherapy. CPT-11 was administered intravenously every 3 weeks (350 mg/m2/day in patients on non-enzyme inducing anticonvulsants [NEIAED]; 600 mg/m2/day in patients on enzyme-inducing anticonvulsants [EIAED]) for 9 weeks (operationally defined as a single cycle). Neurological and neuroradiographic evaluation were performed every 10 weeks.
  
  
  RESULTS
  All patients were evaluable. A median of two cycles of CPT-11 (range 1-4) was administered. CPT-11 related-toxicity (> or = grade 3) included diarrhea (6 occurrences, 19% all cycles administered), granulocytopenia (6, 19%), leukopenia (5, 16%), thrombocytopenia (3, 10%) and anemia (3, 10%). Four patients required transfusion (3 RBC and 1 platelet). One patient developed neutropenic fever without bacteriologic confirmation. No treatment-related deaths occurred. No patient demonstrated a neuroradiographic complete or partial response (PR), 13 patients (81%) demonstrated stable disease but disease progressed after 2 cycles of CPT-11, and 3 patients (19%) had progressive disease (PD) following a single cycle of CPT-11. Time to tumor progression ranged from 2.5 to 5.0 months (median 5.0 months). Survival ranged from 4 to months (median 7.5 months).
  
  
  CONCLUSIONS
  The primary objective was to estimate the 6-month progression-free survival (PFS) after study entry. As no patient demonstrated PFS at 6-months, the study was stopped prematurely as specified by study design. Using CPT-11 in this moderately toxic dose schedule failed to demonstrate efficacy in this cohort of adult patients with recurrent surgery and radiotherapy-refractory meningioma.
authors.affiliation: Department of Interdisciplinary Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, 33612, USA. chambemc@moffitt.usf.edu
authors.forename: Marc C
authors.initials: MC
authors.lastname: Chamberlain
authors.forename: Denice D
authors.initials: DD
authors.lastname: Tsao-Wei
authors.forename: Susan
authors.initials: S
authors.lastname: Groshen
mesh_terms: D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced; D000927:Anticonvulsants / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008579:Meningioma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D016879:Salvage Therapy; D017211:Treatment Failure
chemical_list: D000927:Anticonvulsants; D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin