title: Relationships Between Dose Intensity, Toxicity, and Outcome in Patients with Oligodendroglial Tumors Treated with the PCV Regimen.
abstract: OBJECTIVE
  The drug combination of procarbazine, lomustine (CCNU) and vincristine (PCV) has been associated with efficacy in oligodendroglial gliomas (OG) when added to radiotherapy as the first line of treatment, despite the important toxicity of this treatment schedule. The aim of the present study was to analyze the tolerance, feasibility and impact of the dose intensity of the PCV regimen on outcome for patients with OG.
  
  
  METHODS
  We retrospectively reviewed all patients with OG receiving PCV (CCNU=110 mg/m(2)) who were referred to our two Institutions. The total dose and dose adaptation, cycle delay, dose intensity, toxicity and discontinuation of CCNU were analyzed. Impacts on the outcome were evaluated.
  
  
  RESULTS
  Between 2007 and 2011, 89 patients received PCV. PCV was administered at relapse in 73% of patients. Only 37% completed six cycles, 13.4% discontinued PCV because of toxicity, the other patients discontinued due to tumor progression. Cycle delay and dose reduction were observed for 62% and 70% patients, respectively. Grade 3 and 4 toxicities were observed in 38% and 8% patients, respectively. Among patients whose disease did not progress under the PCV regimen, discontinuation due to toxicity was significantly correlated to poor progression-free survival (PFS: p=0.023, hazard ratio=2.354) and poor overall survival (OS: p=0.021, hazard ratio=5.093). A factor that negatively impacted PFS was the absence of CCNU dose adaptation (p=0.001), while OS was negatively impacted by the absence of cycle delay (p=0.049) and grade 3/4 toxicities (p=0.045).
  
  
  CONCLUSIONS
  Despite the efficacy of the PCV regimen, significant toxicity is associated with this schedule, which appears to impact its feasibility and efficacy. The optimal PCV schedule with the appropriate CCNU dose-intensity adaptation should be redefined taking into account this finding.
authors.affiliation: Department of Neuro-Oncology, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille (APHM), Timone Hospital, Marseille, France emeline.tabouret@gmail.com.
authors.forename: Emeline
authors.initials: E
authors.lastname: Tabouret
authors.affiliation: Department of Neuro-Oncology, Assistance Publique-Hôpitaux de Paris (APHP), Pitié-Salpétrière Hospital, Paris, France.
authors.forename: German
authors.initials: G
authors.lastname: Reyes-Botero
authors.affiliation: Department of Neuro-Oncology, Assistance Publique-Hôpitaux de Paris (APHP), Pitié-Salpétrière Hospital, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Dehais
authors.affiliation: Department of Neuro-Oncology, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille (APHM), Timone Hospital, Marseille, France Department of Pharmacology, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille (APHM), Timone Hospital, Marseille, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Daros
authors.affiliation: Department of Neuro-Oncology, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille (APHM), Timone Hospital, Marseille, France.
authors.forename: Maryline
authors.initials: M
authors.lastname: Barrie
authors.affiliation: Department of Neuro-Oncology, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille (APHM), Timone Hospital, Marseille, France.
authors.forename: Mona
authors.initials: M
authors.lastname: Matta
authors.affiliation: Department of Neuro-Oncology, Assistance Publique-Hôpitaux de Paris (APHP), Pitié-Salpétrière Hospital, Paris, France.
authors.forename: Gregorio
authors.initials: G
authors.lastname: Petrirena
authors.affiliation: Department of Neuro-Oncology, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille (APHM), Timone Hospital, Marseille, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Autran
authors.affiliation: Department of Neuro-Oncology, Assistance Publique-Hôpitaux de Paris (APHP), Pitié-Salpétrière Hospital, Paris, France.
authors.forename: Alberto
authors.initials: A
authors.lastname: Duran
authors.affiliation: Department of Neuro-Oncology, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille (APHM), Timone Hospital, Marseille, France.
authors.forename: Celine
authors.initials: C
authors.lastname: Bequet
authors.affiliation: Department of Neuro-Oncology, Assistance Publique-Hôpitaux de Paris (APHP), Pitié-Salpétrière Hospital, Paris, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Delattre
authors.affiliation: Department of Neuro-Oncology, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille (APHM), Timone Hospital, Marseille, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Chinot
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009837:Oligodendroglioma / Q000188:drug therapy* / Q000473:pathology; D012189:Retrospective Studies; D016896:Treatment Outcome; D014751:Vindesine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D003520:Cyclophosphamide; D002945:Cisplatin; D014751:Vindesine
keywords: Glioma; PCV; feasibility; tolerance