Histologic response of dose-intense chemotherapy with preoperative hypofractionated radiotherapy for patients with high-risk soft tissue sarcomas.
BACKGROUND
The authors studied a dose-intense regimen of epirubicin and ifosfamide with hypofractionated preoperative radiotherapy for high-risk soft tissue sarcomas. The primary objective was estimation of the rate of >or=95% pathologic necrosis.


METHODS
Twenty-five patients with intermediate-grade or high-grade, localized soft tissue sarcomas of the extremity or body wall measuring >5 cm were treated with epirubicin at a dose of 30 mg/m(2)/day on Days 1 to 4 and ifosfamide at a dose of 2.5 g/m(2)/day on Days 1 to 4 every 21 days for 3 preoperative and 3 postoperative cycles. A total of 28 grays of radiation was administered over 8 fractions during Cycle 2 of preoperative therapy (epirubicin was omitted).


RESULTS
Sixteen patients (64%) completed all chemotherapy cycles and the average delivered dose intensity relative to intended therapy was 69%. Twenty-one patients (84%) experienced grade 4 toxicity (using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 2.0]), which was predominantly hematologic. Notable toxicities included neutropenic fever (40%), ifosfamide-induced encephalopathy (24%), and grade 3/4 anemia (64%). Postoperative wound complications requiring a surgical procedure occurred in 20% of patients. The rate of >or=95% pathologic necrosis was 40% (95% confidence interval [95% CI], 21-59%). Estimates of 2-year overall and disease-free survival were 84% (95% CI, 66-100%) and 62% (95% CI, 37-86%), respectively.


CONCLUSIONS
A high rate of >or=95% pathologic necrosis was noted with this aggressive chemoradiotherapy regimen. The occurrence of significant acute toxicities limited the delivery of the intended dose intensity.
Ryan
Christopher W
CW
Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR 97239, USA. ryanc@ohsu.edu
Montag
Anthony G
AG
Hosenpud
Janet R
JR
Samuels
Brian
B
Hayden
James B
JB
Hung
Arthur Y
AY
Mansoor
Atiya
A
Peabody
Terrance D
TD
Mundt
Arno J
AJ
Undevia
Samir
S
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011300:Preoperative Care; D012307:Risk Factors; D012509:Sarcoma / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D016896:Treatment Outcome
D015251:Epirubicin; D007069:Ifosfamide