title: A Phase I Study using low-dose fractionated whole abdominal radiotherapy as a chemopotentiator to full-dose cisplatin for optimally debulked stage III/IV carcinoma of the endometrium.
abstract: OBJECTIVE
  To evaluate the feasibility of combining low-dose fractionated whole abdominal radiation (LDF-WAR) with weekly full-dose cisplatin (FD-CDDP) for patients with stage III/IV endometrial carcinoma.
  
  
  METHODS
  Patients with optimally debulked stage III/IV carcinoma of the endometrium (without extra-abdominal disease) were eligible for the study. Postoperatively, patients received the institutional standard systemic chemotherapy and vaginal brachytherapy. Patients then underwent experimental six weekly cycles of FD-CDDP (40 mg/m², maximum 70 mg IV) followed by LDF-WAR 6-8 hours after initiation of chemotherapy. In a conservative design, 6 patients were accrued to two sequential cohorts of LDF-WAR, at 0.5 Gy/fraction [Fx] (total 3 Gy) and 0.75 Gy/Fx (total 4.5 Gy). Toxicities and laboratory studies were evaluated at each visit.
  
  
  RESULTS
  Twelve patients were enrolled from January 2005 to June 2009 with median follow-up of 13.5 months (range: 5-27 months). Seventy-five percent of enrolled patients had uterine papillary serous histology. Eleven patients at least partially completed therapy (range: 2-6 cycles of FD-CDDP/LDF-WAR) with one additional patient opting out at the higher dose level. Combination therapy overall was well tolerated. Three patients in each cohort experienced grade 3 acute hematologic events with one recorded grade 4 toxicity in the second cohort. Of patients receiving any of the experimental treatment, five have experienced recurrences. Three of these patients were in cohort one and received 0.5 Gy/Fx LDF-WAR.
  
  
  CONCLUSIONS
  Combination therapy with LDF-WAR as a novel chemopotentiator to FD-CDDP is a feasible adjuvant regimen in optimally debulked patients with stage III/IV endometrial carcinoma. Further investigation is warranted to determine treatment efficacy.
authors.affiliation: Department of Obstetrics & Gynecology, Division of Gynecologic Oncology, University of Miami Miller School of Medicine, Miami, FL 33136, USA. AWolfson@med.miami.edu
authors.forename: Dené C
authors.initials: DC
authors.lastname: Wrenn
authors.forename: Kunal
authors.initials: K
authors.lastname: Saigal
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Lucci
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Pearson
authors.forename: Fiona
authors.initials: F
authors.lastname: Simpkins
authors.forename: Samer
authors.initials: S
authors.lastname: Schuman
authors.forename: Leo B
authors.initials: LB
authors.lastname: Twiggs
authors.forename: Gail R
authors.initials: GR
authors.lastname: Walker
authors.forename: Aaron H
authors.initials: AH
authors.lastname: Wolfson
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001918:Brachytherapy; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000627:therapeutic use*; D019583:Dose Fractionation, Radiation; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D005260:Female; D006801:Humans; D007044:Hysterectomy; D008197:Lymph Node Excision; D008875:Middle Aged; D009367:Neoplasm Staging; D010052:Ovariectomy; D017239:Paclitaxel / Q000008:administration & dosage
chemical_list: D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin