title: A phase I trial of oral administration of panobinostat in combination with paclitaxel and carboplatin in patients with solid tumors.
abstract: OBJECTIVE
  To determine the maximum tolerated doses and dose-limiting toxicities of oral panobinostat in combination with paclitaxel and carboplatin when administered to patients with advanced solid tumors.
  
  
  METHODS
  Patients initially received panobinostat twice weekly. Following amendment #1, patients received panobinostat three times weekly. Paclitaxel and carboplatin were administered intravenously on day 1 of each 21-day treatment cycle. Dose escalation continued until the maximum tolerated dose was determined. A total of 10 patients were treated at the recommended phase II dose to further assess safety.
  
  
  RESULTS
  Twenty-one patients were enrolled across four different dose levels. The dose-limiting toxicity of the combination regimen was myelosuppression (neutropenia and thrombocytopenia), which often warranted panobinostat dose omissions or reductions. Nearly two-thirds of the patients experienced grade 4 neutropenia or grade 3 or 4 thrombocytopenia. Non-hematologic toxicities consisted primarily of diarrhea, fatigue, and vomiting, which were mild to moderate in intensity. No QTc prolongation was reported. Three partial responses were confirmed in patients with carcinoma of unknown primary (two patients) and non-small-cell lung cancer (one patient). Eleven additional patients reported stable disease as their best response to treatment.
  
  
  CONCLUSIONS
  The recommended phase II dose is panobinostat 10 mg orally three times weekly in combination with paclitaxel 175 mg/m(2) and carboplatin AUC 5 administered intravenously on day 1 of every 21-day cycle.
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN 37203, USA. suzanne.jones@scresearch.net
authors.forename: Suzanne F
authors.initials: SF
authors.lastname: Jones
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Infante
authors.forename: Dana S
authors.initials: DS
authors.lastname: Thompson
authors.forename: Adil
authors.initials: A
authors.lastname: Mohyuddin
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Bendell
authors.forename: Denise A
authors.initials: DA
authors.lastname: Yardley
authors.forename: Howard A
authors.initials: HA
authors.lastname: Burris
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage; D007211:Indoles; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D000077767:Panobinostat; D016896:Treatment Outcome
chemical_list: D006877:Hydroxamic Acids; D007211:Indoles; D000077767:Panobinostat; D016190:Carboplatin; D017239:Paclitaxel