title: Paclitaxel poliglumex and carboplatin as first-line therapy in ovarian, peritoneal or fallopian tube cancer: a phase I and feasibility trial of the Gynecologic Oncology Group.
abstract: OBJECTIVE
  To estimate the maximum tolerated dose (MTD) of paclitaxel poliglumex (PPX) in combination with carboplatin in patients with chemotherapy-naive ovarian, primary peritoneal or fallopian tube cancer, and to assess the feasibility of administering multiple cycles of this regimen.
  
  
  METHODS
  The first 11 patients were treated in a standard 3 + 3 dose-seeking design, with carboplatin held constant at area under the curve (AUC) of 6 and PPX at 225, 175 or 135 mg/m(2). Pharmacokinetics of PPX and carboplatin were evaluated during this dose-seeking component of the trial. MTD was defined by acute dose-limiting toxicities (DLT) in the first cycle. Twenty additional evaluable patients were treated at the estimated MTD to assess the feasibility of this regimen over >or=4cycles.
  
  
  RESULTS
  PPX at 225 mg/m(2) resulted in DLT in 2/3 patients, and was de-escalated first to 175 mg/m(2) and then to 135 mg/m(2). PPX slowly hydrolyzed to paclitaxel and did not alter the pharmacokinetics of carboplatin. DLT within the first 4-cycles were observed in 3 patients (15%) treated at the MTD: neutropenia > 2weeks (2), febrile neutropenia (1). Nineteen patients (95%) experienced grade 4 neutropenia. Sixteen patients (80%) had at least one episode of grade 3 thrombocytopenia. Three patients (15%) had grade 2 and one had grade 3 peripheral neuropathy. Complete response by CA-125 was 75%.
  
  
  CONCLUSIONS
  The recommended dose of PPX of 135 mg/m(2) with carboplatin (AUC = 6) in newly diagnosed ovarian cancer was feasible for multiple cycles, but hematologic toxicity was greater compared with standard carboplatin and 3-hour paclitaxel.
authors.affiliation: Section of Gynecologic Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111-2497, USA. mark.morgan@fccc.edu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Morgan
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Darcy
authors.forename: Peter G
authors.initials: PG
authors.lastname: Rose
authors.forename: Koen
authors.initials: K
authors.lastname: DeGeest
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bookman
authors.forename: James K
authors.initials: JK
authors.lastname: Aikins
authors.forename: Michael W
authors.initials: MW
authors.lastname: Sill
authors.forename: Robert S
authors.initials: RS
authors.lastname: Mannel
authors.forename: Cecilia
authors.initials: C
authors.lastname: Allievi
authors.forename: Merrill J
authors.initials: MJ
authors.lastname: Egorin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D015331:Cohort Studies; D004347:Drug Interactions; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011099:Polyglutamic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics
chemical_list: D011099:Polyglutamic Acid; D016190:Carboplatin; D017239:Paclitaxel; C509139:paclitaxel poliglumex