title: Phase I study of intravenous (IV) docetaxel and intraperitoneal (IP) oxaliplatin in recurrent ovarian and fallopian tube cancer.
abstract: OBJECTIVE
  The primary objective was to define the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of IV docetaxel and IP oxaliplatin in women with recurrent ovarian (OV), fallopian tube (FT) or peritoneal (PP) cancer. Secondary objectives included response rate, time to progression, pharmacokinetics (PK) and quality of life (QoL).
  
  
  METHODS
  Patients received docetaxel 75mg/m(2) IV day (d) 1 and oxaliplatin escalating from 50mg/m(2) IP d2 every 3weeks using a 3+3 design. Treatment continued until disease progression, remission, or intolerable toxicity. Plasma and IP samples were taken to determine drug concentrations. MD Anderson Symptom Inventory and symptom interference scale were completed weekly.
  
  
  RESULTS
  Thirteen patients were included. Median number of cycles was 6 (range 1-10). Ten patients had measureable disease. Best response was partial response (PR-2), stable disease (SD-7), and progressive disease (PD-1). Twenty-one Grades 3-4 toxicities were noted, commonly hematologic. Two patients had DLTs: prolonged neutropenia (1) and abdominal pain (1). MTD was d1 docetaxel 75mg/m(2) IV and d2 oxaliplatin 50mg/m(2) IP. Symptom burden peaked week one and returned to baseline by week two of each cycle on dose level 1. Dose level 2 had persistently high symptom burden and interference. At IP oxaliplatin doses of 50mg/m(2), total unbound drug exposure (AUC) averaged 8 times larger and Cmax reached concentrations 50-fold greater in IP fluid compared to plasma.
  
  
  CONCLUSIONS
  Docetaxel 75mg/m(2) IV d1 and oxaliplatin 50mg/m(2) IP d2 is the MTD. Most patients had PR or SD. Patient-reported outcomes demonstrate temporary but tolerable decrements in QoL. IP oxaliplatin provides PK advantages over IV administration.
authors.affiliation: Division of Gynecologic Oncology, Magee-Womens Hospital of UPMC, Pittsburgh, PA, United States. Electronic address: taylorse2@mail.magee.edu.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Taylor
authors.affiliation: School of Nursing, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Ruosha
authors.initials: R
authors.lastname: Li
authors.affiliation: Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, United States.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Petschauer
authors.affiliation: School of Nursing, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Heidi
authors.initials: H
authors.lastname: Donovan
authors.affiliation: Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, United States.
authors.forename: Sara
authors.initials: S
authors.lastname: O'Neal
authors.affiliation: Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, United States.
authors.forename: Amanda W
authors.initials: AW
authors.lastname: Keeler
authors.affiliation: Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, United States.
authors.forename: William C
authors.initials: WC
authors.lastname: Zamboni
authors.affiliation: Division of Gynecologic Oncology, Magee-Womens Hospital of UPMC, Pittsburgh, PA, United States.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Edwards
authors.affiliation: University of Arkansas for Medical Sciences, Little Rock, AR, United States.
authors.forename: Kristin K
authors.initials: KK
authors.lastname: Zorn
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007263:Infusions, Parenteral; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D000077150:Oxaliplatin; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D009944:Organoplatinum Compounds; D043823:Taxoids; D000077150:Oxaliplatin; D000077143:Docetaxel
keywords: Intraperitoneal chemotherapy; Ovarian cancer; Phase I trial; Recurrent