title: Procoagulant inhibitory properties of paclitaxel poliglumex.
abstract: BACKGROUND
  In Phase I evaluation of CT-2103 (paclitaxel poliglumex), prolongation of prothrombin time (PT) and activated thromboplastin time (aPTT) was observed, without clinical consequence, with doses 1.3-1.5 times higher than the current clinical dose of 175 mg/m(2). This Phase I, open-label, nonrandomized pilot study was performed to study the effect of the standard dose regimen on blood coagulation.
  
  
  METHODS
  Seven previously treated solid tumor patients received CT-2103 175 mg/m(2) intravenously on day 1 of 21-day cycles for a mean of 5.4 cycles (median 4, range 2-14). Plasma samples were collected for cycle 1 predose and at hours 1, 24, 48, and 72 after the end of administration for drug levels, and for PT and aPTT assays.
  
  
  RESULTS
  No coagulopathy-related adverse events were documented. Bleeding time remained normal in the six patients tested, with transient increases in PT and aPTT noted but resolving within 72 hours. Titration studies at 100 μg/mL of CT-2103 (corresponding to the standard clinical dose) prolonged PT and aPTT clotting times, produced a modest dose-dependent reduction of thrombin and factor Xa, and no significant changes in factors IXa, XIa, or XIIa. Two patients achieved stable disease for ≥10 cycles.
  
  
  CONCLUSIONS
  CT-2103 is associated with transient prolongation of PT and aPTT without clinical sequelae.
authors.affiliation: Mary Crowley Cancer Research Centers, Dallas, TX, USA. jnemunaitis@marycrowley.org
authors.forename: John
authors.initials: J
authors.lastname: Nemunaitis
authors.forename: Neil
authors.initials: N
authors.lastname: Senzer
authors.forename: Barry
authors.initials: B
authors.lastname: Cooper
authors.forename: Michael
authors.initials: M
authors.lastname: Nemunaitis
authors.forename: Cynthia
authors.initials: C
authors.lastname: Bedell
authors.forename: Jack W
authors.initials: JW
authors.lastname: Singer
authors.forename: Fred B
authors.initials: FB
authors.lastname: Oldham