title: Glioblastoma treatment: bypassing the toxicity of platinum compounds by using liposomal formulation and increasing treatment efficiency with concomitant radiotherapy.
abstract: OBJECTIVE
  Treatments of glioblastoma with cisplatin or oxaliplatin only marginally improve the overall survival of patients and cause important side effects. To prevent adverse effects, improve delivery, and optimize the tumor response to treatment in combination with radiotherapy, a potential approach consists of incorporating the platinum agent in a liposome.
  
  
  METHODS
  In this study, cisplatin, oxaliplatin, carboplatin, Lipoplatin (the liposomal formulation of cisplatin), and Lipoxal (the liposomal formulation of oxaliplatin) were tested on F98 glioma orthotopically implanted in Fischer rats. The platinum compounds were administered by intracarotid infusion and were assessed for the ability to reduce toxicity, improve cancer cell uptake, and increase survival of animals when combined or not combined with radiotherapy.
  
  
  RESULTS
  The tumor uptake was 2.4-fold more important for Lipoxal than the liposome-free oxaliplatin. Lipoxal also improved the specificity of oxaliplatin as shown by a higher ratio of tumor to right hemisphere uptake. Surprisingly, Lipoplatin led to lower tumor uptake compared with cisplatin. However, Lipoplatin had the advantage of largely reducing the toxicity of cisplatin and allowed us to capitalize on the anticancer activity of this agent.
  
  
  CONCLUSIONS
  Among the five platinum compounds tested, carboplatin showed the best increase in survival when combined with radiation for treatment of glioma implanted in Fischer rats.
authors.affiliation: Center for Research in Radiotherapy, Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, Québec, Canada.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Charest
authors.forename: Léon
authors.initials: L
authors.lastname: Sanche
authors.forename: David
authors.initials: D
authors.lastname: Fortin
authors.forename: David
authors.initials: D
authors.lastname: Mathieu
authors.forename: Benoit
authors.initials: B
authors.lastname: Paquette
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D002339:Carotid Arteries; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D003131:Combined Modality Therapy / Q000379:methods; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D007261:Infusions, Intra-Arterial / Q000379:methods; D008081:Liposomes; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000077150:Oxaliplatin; D016634:Radiosurgery / Q000379:methods; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D009944:Organoplatinum Compounds; C503131:lipoplatin; D000077150:Oxaliplatin; D016190:Carboplatin; D002945:Cisplatin