Phase I trial of preoperative concurrent doxorubicin and radiation therapy, surgical resection, and intraoperative electron-beam radiation therapy for patients with localized retroperitoneal sarcoma.
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.
Pisters
Peter W T
PW
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
Ballo
Matthew T
MT
Fenstermacher
Mark J
MJ
Feig
Barry W
BW
Hunt
Kelly K
KK
Raymond
Kevin A
KA
Burgess
Michael A
MA
Zagars
Gunar K
GK
Pollock
Raphael E
RE
Benjamin
Robert S
RS
Patel
Shreyaskumar R
SR
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*
D004317:Doxorubicin