title: Phase I trial of carboplatin and etoposide in combination with panobinostat in patients with lung cancer.
abstract: A phase I trial consisting of panobinostat (a HDAC inhibitor), carboplatin and etoposide was conducted in patients with lung cancer.
  
  
  METHODS
  Patients received carboplatin AUC5 on day 1 and etoposide 100 mg/m(2) on days 1, 2 and 3, every 21 days. Concurrent oral panobinostat was given 3 times weekly on a 2-weeks-on and 1-week-off schedule during the 4-6 cycles of chemotherapy and then continued as maintenance therapy.
  
  
  RESULTS
  Six evaluable patients were treated at the first dose level of panobinostat (10 mg). Dose-limiting toxicity occurred in two patients (33%) during the first cycle. One patient developed grade 4 thrombocytopenia and another grade 4 febrile neutropenia. Therefore, the study was suspended based on the pre-specified study design. No recommended phase II starting dose was established.
  
  
  CONCLUSIONS
  The addition of panobinostat to carboplatin and etoposide was not tolerable at the lowest dose level tested in this trial. Further research and development into this combination is not recommended.
authors.affiliation: University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue (555), Pittsburgh, PA 15232, U.S.A. tarhiniaa@upmc.edu.
authors.forename: Ahmad A
authors.initials: AA
authors.lastname: Tarhini
authors.forename: Haris
authors.initials: H
authors.lastname: Zahoor
authors.forename: Brian
authors.initials: B
authors.lastname: McLaughlin
authors.forename: William E
authors.initials: WE
authors.lastname: Gooding
authors.forename: John C
authors.initials: JC
authors.lastname: Schmitz
authors.forename: Jill M
authors.initials: JM
authors.lastname: Siegfried
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
authors.forename: Athanassios
authors.initials: A
authors.lastname: Argiris
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D064146:Chemotherapy-Induced Febrile Neutropenia / Q000209:etiology; D057239:Early Termination of Clinical Trials; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage; D007211:Indoles / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D000077767:Panobinostat
chemical_list: D006877:Hydroxamic Acids; D007211:Indoles; D005047:Etoposide; D000077767:Panobinostat; D016190:Carboplatin
keywords: Lung cancer; carboplatin; etoposide; panobinostat