title: Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane) on three treatment schedules in patients with solid tumors.
abstract: OBJECTIVE
  Albumin-bound paclitaxel, ABI-007 (Abraxane((R))), has a different toxicity profile than solvent-based paclitaxel, including a lower rate of severe neutropenia. The combination of ABI-007 and carboplatin may have significant activity in a variety of tumor types including non-small and small cell lung cancer, ovarian cancer, and breast cancer. The purpose of this study was to determine the maximum tolerated dose (MTD) of ABI-007, on three different schedules in combination with carboplatin.
  
  
  METHODS
  Forty-one patients with solid tumors were enrolled, and received ABI-007 in combination with carboplatin AUC of 6 on day 1. Group A received ABI-007 at doses ranging from 220 to 340 mg/m(2) on day 1 every 21 days; group B received ABI-007 at 100 or 125 mg/m(2) on days 1, 8, and 15 every 28 days; and group C received ABI-007 125 or 150 mg/m(2) on days 1 and 8 every 21 days. Dose-limiting toxicities were assessed after the first cycle. Doses were escalated in cohorts of three to six patients. Fifteen patients participated in a pharmacokinetic study investigating the effects of the sequence of infusion. ABI-007 was infused first followed by carboplatin in cycle 1, and vice versa in cycle 2.
  
  
  RESULTS
  The MTD of ABI-007 in combination with carboplatin was 300, 100, and 125 mg/m(2) in groups A, B, and C, respectively. Myelosuppression was the primary dose limiting toxicity. No unexpected or new toxicities were reported. Sequence of infusion did not affect either the pharmacokinetics of ABI-007 or the degree of neutropenia. Responses were seen in melanoma, lung, bladder, esophageal, pancreatic, breast cancer, and cancer of unknown primary.
  
  
  CONCLUSIONS
  The recommended dose for phase II studies of ABI-007 in combination with carboplatin (AUC of 6) is 300, 100, 125 mg/m(2) for the schedules A, B, and C, respectively. The combination of ABI-007 and carboplatin is well tolerated and active in this heavily pretreated patient population.
authors.affiliation: Department of Hematology/Oncology, Developmental Therapeutics Group Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Stinchcombe
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
authors.forename: Christine M
authors.initials: CM
authors.lastname: Walko
authors.forename: Bert H
authors.initials: BH
authors.lastname: O'Neil
authors.forename: Frances A
authors.initials: FA
authors.lastname: Collichio
authors.forename: Anastasia
authors.initials: A
authors.lastname: Ivanova
authors.forename: Hua
authors.initials: H
authors.lastname: Mu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hawkins
authors.forename: Richard M
authors.initials: RM
authors.lastname: Goldberg
authors.forename: Celeste
authors.initials: C
authors.lastname: Lindley
authors.forename: E Claire
authors.initials: EC
authors.lastname: Dees
mesh_terms: D000328:Adult; D000368:Aged; D000068196:Albumin-Bound Paclitaxel; D000418:Albumins / Q000008:administration & dosage / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001773:Blood Cells / Q000187:drug effects; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000188:drug therapy; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D016190:Carboplatin; D017239:Paclitaxel