title: Phase I trial of preoperative concurrent doxorubicin and radiation therapy, surgical resection, and intraoperative electron-beam radiation therapy for patients with localized retroperitoneal sarcoma.
abstract: OBJECTIVE
  The primary objective of this phase I trial was to define the maximum-tolerated dose of external-beam radiation with concurrent fixed-dose continuous-infusion doxorubicin followed by surgical resection and electron-beam intraoperative radiation therapy (EB-IORT) for patients with localized, potentially resectable retroperitoneal sarcomas (RPS).
  
  
  METHODS
  Thirty-five patients with radiographically resectable primary or recurrent intermediate- or high-grade RPS were treated. Doxorubicin was administered each week for 4 or 5 weeks as an initial bolus (4 mg/m2) followed by a 4-day continuous infusion (4 mg/m2/d). Concurrent radiation therapy was administered in escalating doses of 18.0, 30.6, 36.0, 41.4, 46.8, or 50.4 Gy in 1.8-Gy fractions. Radiographic restaging was performed 4 to 8 weeks after chemoradiation, and patients with localized disease underwent surgical resection with EB-IORT (15 Gy).
  
  
  RESULTS
  Chemoradiation was completed as outpatient therapy in 31 patients (89%); four patients required hospital admission during chemoradiation or in the postchemoradiation preoperative period. At the highest radiation dose of 50.4 Gy, two (18%) of 11 patients had grade 3 or 4 nausea. Twenty-nine patients (83%) underwent laparotomy; six patients had interval disease progression and did not undergo surgery. Grossly complete resection (R0 or R1) was performed in 26 (90%) of 29 patients who had surgery. EB-IORT was feasible and successfully administered to 22 patients who had R0 or R1 resections.
  
  
  CONCLUSIONS
  Preoperative chemoradiation, surgical resection, and EB-IORT are feasible for patients with RPS. Preoperative external-beam radiation can be administered to a total dose of 50.4 Gy with continuous-infusion doxorubicin.
authors.affiliation: Department of Surgical Oncology, Unit 444, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030-4009, USA. ppisters@mdanderson.org
authors.forename: Peter W T
authors.initials: PW
authors.lastname: Pisters
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Ballo
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Fenstermacher
authors.forename: Barry W
authors.initials: BW
authors.lastname: Feig
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Hunt
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Raymond
authors.forename: Michael A
authors.initials: MA
authors.lastname: Burgess
authors.forename: Gunar K
authors.initials: GK
authors.lastname: Zagars
authors.forename: Raphael E
authors.initials: RE
authors.lastname: Pollock
authors.forename: Robert S
authors.initials: RS
authors.lastname: Benjamin
authors.forename: Shreyaskumar R
authors.initials: SR
authors.lastname: Patel
mesh_terms: D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007430:Intraoperative Care; D008297:Male; D008875:Middle Aged; D011300:Preoperative Care; D011879:Radiotherapy Dosage; D012186:Retroperitoneal Neoplasms / Q000601:surgery / Q000628:therapy*; D012509:Sarcoma / Q000601:surgery / Q000628:therapy*
chemical_list: D004317:Doxorubicin