title: Phase I study of intravenously administered ATI-1123, a liposomal docetaxel formulation in patients with advanced solid tumors.
abstract: OBJECTIVE
  ATI-1123 is a liposomal formulation of docetaxel and may be administered without the premedications and hypersensitivity reactions. This Phase I study examines the safety, tolerability, pharmacokinetics (PKs), and antitumor activity of ATI-1123.
  
  
  METHODS
  Patients with advanced solid malignancies received escalating doses of ATI-1123 intravenously over 1-h every 3 weeks. The dosing commenced using an accelerated titration design and was followed by a modified 3 + 3 Fibonacci schema to determine maximally tolerated dose (MTD). Plasma was analyzed for encapsulated/non-encapsulated docetaxel; PK analyses were performed using model independent method. Response was assessed using RECIST criteria.
  
  
  RESULTS
  In total, 29 patients received doses ranging from 15 to 110 mg/m(2). At 110 mg/m(2), two of six patients experienced dose-limiting toxicities including grade 3 stomatitis and febrile neutropenia. The 90 mg/m(2) cohort was expanded to ten patients and identified as the MTD. The most common adverse events were fatigue, nausea, neutropenia, anemia, anorexia, and diarrhea. ATI-1123 exhibited linear and dose proportional PKs. One patient with lung cancer had confirmed partial response, and stable disease was observed in 75 % patients.
  
  
  CONCLUSIONS
  ATI-1123 demonstrated an acceptable tolerability and favorable PK profile in patients with solid tumors. Our results provide support for Phase II trials to determine the antitumor activity of this drug.
authors.affiliation: Institute for Drug Development, Cancer Therapy and Research Center (CTRC), University of Texas Health Science Center, San Antonio, TX, USA, Mahalingam@uthscsa.edu.
authors.forename: Devalingam
authors.initials: D
authors.lastname: Mahalingam
authors.forename: John J
authors.initials: JJ
authors.lastname: Nemunaitis
authors.forename: Laeeq
authors.initials: L
authors.lastname: Malik
authors.forename: John
authors.initials: J
authors.lastname: Sarantopoulos
authors.forename: Steven
authors.initials: S
authors.lastname: Weitman
authors.forename: Kamalesh
authors.initials: K
authors.lastname: Sankhala
authors.forename: Jessica
authors.initials: J
authors.lastname: Hart
authors.forename: Ahmed
authors.initials: A
authors.lastname: Kousba
authors.forename: Nicole S
authors.initials: NS
authors.lastname: Gallegos
authors.forename: Gavin
authors.initials: G
authors.lastname: Anderson
authors.forename: John
authors.initials: J
authors.lastname: Charles
authors.forename: Jon M
authors.initials: JM
authors.lastname: Rogers
authors.forename: Neil N
authors.initials: NN
authors.lastname: Senzer
authors.forename: Alain C
authors.initials: AC
authors.lastname: Mita
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008081:Liposomes; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D043823:Taxoids; D000077143:Docetaxel