title: A phase I trial of tailored radiation therapy with concomitant cetuximab and cisplatin in the treatment of patients with cervical cancer: A gynecologic oncology group study.
abstract: BACKGROUND
  Epithelial growth factor receptor over-expression correlates with poor outcomes in cervical cancer. This study assessed the safety of chemoradiation with cetuximab in the treatment of women with newly diagnosed locally advanced cervical cancer.
  
  
  METHODS
  Patients received weekly cisplatin 30 and 40 mg/m(2) [dose level (DL) 1 and 2] and cetuximab 400mg/m(2) loading dose and then 250 mg/m(2) for a total of six weeks with radiotherapy (RT). Patients with nodal metastases received extended field radiation therapy (EFRT). At the maximum tolerated dose, feasibility was evaluated in a 20 patient two-stage, sequential design.
  
  
  RESULTS
  In patients receiving pelvic RT, seven were treated at DL 1 with one dose-limiting toxicity (DLT) (febrile neutropenia with grade 3 diarrhea) and three at DL 2 with two DLTs (grade 3 rash and delay in RT >8 weeks). The feasibility phase was opened at DL1. Of the 21 patients treated there was one DLT (grade 4 CVA). Median RT duration was 50 days (range, 42-70). In patients receiving EFRT, nine were treated at DL 1 with 1 DLT (grade 3 mucositis) and 24 in the feasibility phase with eight DLTs [delay in RT >8 weeks due to toxicity (2) and one each with grade 3 or 4 small bowel obstruction, embolism, mucositis, mucositis with hypokalemia, pain with headache, and platelets with mucositis and headache]. Median EFRT duration was 56 days (range, 36-74).
  
  
  CONCLUSIONS
  For patients receiving pelvic RT, cisplatin and cetuximab were feasible. For patients receiving EFRT, combination of cisplatin and cetuximab was not feasible.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Oklahoma, Oklahoma City, OK 73190, USA. Kathleen-moore@ouhsc.edu
authors.forename: Kathleen N
authors.initials: KN
authors.lastname: Moore
authors.forename: Michael W
authors.initials: MW
authors.lastname: Sill
authors.forename: David S
authors.initials: DS
authors.lastname: Miller
authors.forename: Carolyn
authors.initials: C
authors.lastname: McCourt
authors.forename: Koen
authors.initials: K
authors.lastname: De Geest
authors.forename: Peter G
authors.initials: PG
authors.lastname: Rose
authors.forename: Higinia R
authors.initials: HR
authors.lastname: Cardenes
authors.forename: Robert S
authors.initials: RS
authors.lastname: Mannel
authors.forename: John H
authors.initials: JH
authors.lastname: Farley
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Schilder
authors.forename: Paula M
authors.initials: PM
authors.lastname: Fracasso
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068818:Cetuximab; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D002583:Uterine Cervical Neoplasms / Q000628:therapy*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab; D002945:Cisplatin