Phase I trial of preoperative doxorubicin-based concurrent chemoradiation and surgical resection for localized extremity and body wall soft tissue sarcomas.
OBJECTIVE
The primary objective of this phase I trial was to define the maximum-tolerated dose of continuous-infusion doxorubicin administered with standard preoperative radiation for patients with localized, potentially resectable soft tissue sarcomas of the extremities or body wall.


METHODS
Twenty-seven patients with radiographically resectable intermediate- or high-grade soft tissue sarcomas were treated. Preoperative external-beam radiation was administered in 25 2-Gy fractions (total dose, 50 Gy). Concurrent continuous-infusion doxorubicin was administered by an initial bolus (4 mg/m(2)) and subsequent 4-day continuous infusion (12.5, 15.0, 17.5, or 20.0 mg/m(2)/wk). Radiographic restaging was performed 4 to 7 weeks after chemoradiation, and patients with localized disease underwent surgical resection.


RESULTS
Chemoradiation was completed as an outpatient procedure in 25 patients (93%). The maximum-tolerated dose of continuous-infusion doxorubicin combined with standard preoperative radiation was 17.5 mg/m(2)/wk; at this dose level, seven (30%) of 23 patients had grade 3 dermatologic toxicity. Macroscopically complete resection (R0 or R1) was performed in all 26 patients who underwent surgery. Among 22 patients who were treated with doxorubicin 17.5/mg/m(2)/wk with concurrent radiation and subsequent surgery, 11 patients (50%) had 90% or greater tumor necrosis, including two patients who had complete pathologic responses.


CONCLUSIONS
Preoperative doxorubicin-based chemoradiation appears safe and feasible. The maximum-tolerated dose of continuous-infusion doxorubicin with standard preoperative radiation was 17.5 mg/m(2)/wk. Pathologic response rates with this regimen are encouraging.
Pisters
Peter W T
PW
Multidisciplinary Sarcoma Center, Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, Texas 77030-4009, USA. ppisters@mdanderson.org
Patel
Shreyaskumar R
SR
Prieto
Victor G
VG
Thall
Peter F
PF
Lewis
Valerae O
VO
Feig
Barry W
BW
Hunt
Kelly K
KK
Yasko
Alan W
AW
Lin
Patrick P
PP
Jacobson
Marc G
MG
Burgess
Michael A
MA
Pollock
Raphael E
RE
Zagars
Gunar K
GK
Benjamin
Robert S
RS
Ballo
Matthew T
MT
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009336:Necrosis; D020360:Neoadjuvant Therapy; D012509:Sarcoma / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin