title: A phase I study of panobinostat in combination with gemcitabine in the treatment of solid tumors.
abstract: OBJECTIVE
  To evaluate the safety and tolerability of the combination of orally administered panobinostat with gemcitabine in patients with advanced solid tumors.
  
  
  METHODS
  Patients received oral panobinostat administered 2 or 3 times weekly (continuous or intermittent dosing in combination with intravenous gemcitabine administered on days 1, 8, and 15 every 28 days or on days 1 and 8 every 21 days). Toxicity assessments were ongoing, and disease assessments were repeated every 2 treatment cycles.
  
  
  RESULTS
  A total of 63 cycles of study treatment were administered to 17 patients over 5 different dose levels. Dose-limiting toxicities occurred at all dose levels. In all instances, dose-limiting toxicities were due to grade 4 myelosuppression or myelosuppression warranting dose modifications during the first treatment cycle. Nonhematologic toxicities were mild to moderate in intensity and consisted of anorexia, constipation, diarrhea, fatigue, nausea, vomiting, and rash. One patient with ovarian cancer had an unconfirmed partial response, and 5 patients had stable disease lasting more than 4 cycles.
  
  
  CONCLUSIONS
  Dosing of the combination regimen of panobinostat and gemcitabine is limited by myelosuppression. The recommended doses for further study are intermittent oral panobinostat administered at a dose of 10 mg 3 times weekly for 2 weeks in combination with gemcitabine 800 mg/m2 administered intravenously on days 1 and 8 every 21 days.
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN 37203, USA.
authors.forename: Suzanne F
authors.initials: SF
authors.lastname: Jones
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Bendell
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Infante
authors.forename: David R
authors.initials: DR
authors.lastname: Spigel
authors.forename: Dana S
authors.initials: DS
authors.lastname: Thompson
authors.forename: Denise A
authors.initials: DA
authors.lastname: Yardley
authors.forename: F Anthony
authors.initials: FA
authors.lastname: Greco
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Murphy
authors.forename: Howard A
authors.initials: HA
authors.lastname: Burris
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000009:adverse effects; D007211:Indoles; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D000077767:Panobinostat; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D006877:Hydroxamic Acids; D007211:Indoles; D003841:Deoxycytidine; D000077767:Panobinostat; D000093542:Gemcitabine