title: Post-operative combined radiation and chemotherapy with temozolomide and irinotecan in patients with high-grade astrocytic tumors. A phase II study with biomarker evaluation.
abstract: BACKGROUND
  Clinical studies have shown that temozolomide (TMZ) and irinotecan demonstrate activity in high grade astrocytic tumors (HGAT). However, the optimal schedule of administration is unknown.
  
  
  METHODS
  In the present study, a total of 45 HGAT patients, 38 with glioblastoma multiforme (GBM) and 7 with anaplastic astrocytoma (AA), were treated with TMZ, 150 mg/m(2) on days 1-5, followed by irinotecan, 150 mg/m(2) on days 6 and 17, every 4 weeks for 6 cycles or until the occurrence of unacceptable toxicity or disease progression. Radiation therapy (60 Gy) was initiated on the first day of treatment.
  
  
  RESULTS
  Twenty-two patients completed six cycles of treatment. Most frequently recorded side-effects included neutropenia (37%), nausea/vomiting (66%), diarrhea (31%) and infection (44%). Five episodes of vaso-occlusive disease, all of them fatal, were observed. After a median follow-up of 49.8 months, median progression-free survival for patients with GBM was 7.7 months, while median overall survival was 12.8 months. There were six long-term survivors, three of them with GBM. Two out of the five biomarkers studied, epidermal growth factor receptor (EGFR) and vascular endothelial growth factor-C (VEGF-C), were found to be overexpressed in 74% of the tumors, however they had no predictive value for progression-free or overall survival.
  
  
  CONCLUSIONS
  The combination of TMZ and irinotecan, as administered in this study, was accompanied by high rates of toxicity, especially myelotoxicity and infection. Further development of this regimen in the treatment of HGAT is not recommended.
authors.affiliation: Department of Medical Oncology, Aristotle University of Thessaloniki, Thessaloniki, Greece. fountzil@med.auth.gr
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
authors.forename: George
authors.initials: G
authors.lastname: Karkavelas
authors.forename: Anna
authors.initials: A
authors.lastname: Kalogera-Fountzila
authors.forename: Maria
authors.initials: M
authors.lastname: Karina
authors.forename: Michail
authors.initials: M
authors.lastname: Ignatiadis
authors.forename: George
authors.initials: G
authors.lastname: Koukoulis
authors.forename: George
authors.initials: G
authors.lastname: Plataniotis
authors.forename: Despina
authors.initials: D
authors.lastname: Misailidou
authors.forename: Mattheos
authors.initials: M
authors.lastname: Bobos
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pectasides
authors.forename: Evangelia
authors.initials: E
authors.lastname: Razis
authors.forename: Antonios
authors.initials: A
authors.lastname: Karavelis
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Selviaridis
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy / Q000628:therapy*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy / Q000628:therapy*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D003131:Combined Modality Therapy; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005240:Feasibility Studies; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D000077146:Irinotecan; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis; D010349:Patient Compliance; D011182:Postoperative Care; D000077204:Temozolomide; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D042582:Vascular Endothelial Growth Factor C; D000077146:Irinotecan; D003606:Dacarbazine; D051546:Cyclooxygenase 2; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D002166:Camptothecin; D000077204:Temozolomide