title: A phase I study of IV doxorubicin plus intraperitoneal (IP) paclitaxel and IV or IP cisplatin in endometrial cancer patients at high risk for peritoneal failure (GOG 9920): an NRG Oncology/Gynecologic Oncology Group study.
abstract: OBJECTIVE
  To determine the maximum tolerated dose (MTD) of a modified paclitaxel/doxorubicin/cisplatin (TAP) regimen which incorporated intraperitoneal (IP) paclitaxel or IP paclitaxel/cisplatin in advanced endometrial cancer.
  
  
  METHODS
  Patients (pts) with FIGO (1998) Stage IIIA/IIIC with positive cytologic washings/ascites, adnexa, or serosa or Stage IV (intraperitoneal disease spread), histologically confirmed endometrial cancer were eligible. The study was designed as a phase I, 3+3 dose escalation study evaluating 5 dose levels (DL). All pts received cycles 1-2 with IV TAP, and cycles 3-6 with IV/IP therapy, on a 21day schedule. Adverse events were evaluated on cycles 3-4 for dose limiting toxicity (DLT) and dose escalation decisions.
  
  
  RESULTS
  Twenty-one pts were enrolled, of which 17 were evaluable for DLT. Most pts had Stage IV disease (76%) and serous/clear cell histology (59%). The MTD was determined to be DL 3 (cycles 3-6 including paclitaxel 90mg/m(2) IP, doxorubicin 45mg/m(2) IV, cisplatin 50mg/m(2)). Three DLT events occurred and were related to grades 3-4 metabolic toxicities. There was one grade 2 sensory neuropathy event and myelosupression was tolerable without the use of G-CSF. 88% of evaluable pts completed 6cycles of therapy. With a median follow-up of 22months, 46% of patients remain progression-free at 2years.
  
  
  CONCLUSIONS
  We described an IV/IP based modification of a standard TAP regimen in endometrial cancer. Based on the high rate of completing 6cycles of therapy, low rates of neuropathy, and promising PFS, further study of IP therapy in endometrial cancer is warranted.
authors.affiliation: University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States. Electronic address: scott-mcmeekin@ouhsc.edu.
authors.forename: D Scott
authors.initials: DS
authors.lastname: McMeekin
authors.affiliation: NRG Oncology Statistics and Data Management Center, Buffalo, NY, United States. Electronic address: msill@gogstats.org.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Sill
authors.affiliation: University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States. Electronic address: joan-walker@ouhsc.edu.
authors.forename: Joan L
authors.initials: JL
authors.lastname: Walker
authors.affiliation: University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States. Electronic address: kathleen-moore@ouhsc.edu.
authors.forename: Kathleen N
authors.initials: KN
authors.lastname: Moore
authors.affiliation: Case Western Reserve University, Cleveland, OH, United States. Electronic address: steven.waggoner@uhhospitals.org.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Waggoner
authors.affiliation: Washington University School of Medicine, St. Louis, MO, United States. Electronic address: thakerp@wudosis.wustl.edu.
authors.forename: Premal H
authors.initials: PH
authors.lastname: Thaker
authors.affiliation: Women and Infants, Providence, RI, United States. Electronic address: trizack@wihri.org.
authors.forename: Tina
authors.initials: T
authors.lastname: Rizack
authors.affiliation: The Hospital of Central Connecticut, New Britain, CT, United States. Electronic address: james.hoffman@hhchealth.org.
authors.forename: James S
authors.initials: JS
authors.lastname: Hoffman
authors.affiliation: University of Virginia, Charlottesville, VA, United States. Electronic address: fracasso@virginia.edu.
authors.forename: Paula M
authors.initials: PM
authors.lastname: Fracasso
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage
chemical_list: D004317:Doxorubicin; D017239:Paclitaxel; D002945:Cisplatin
keywords: Cisplatin; Doxorubicin plus intraperitoneal; Endometrial cancer patients; NRG Oncology