Preoperative concurrent radiotherapy with capecitabine before total mesorectal excision in locally advanced rectal cancer.
OBJECTIVE
Capecitabine is an attractive radiosensitizer which can be tumor specific. This study was undertaken to evaluate the toxicity and efficacy of oral capecitabine when used with preoperative radiation therapy.


METHODS
We conducted a prospective Phase II trial to assess the pathologic response, sphincter preservation effect, and acute toxicity of preoperative chemoradiation (CRT) in locally advanced (uT3-4/N +) but resectable adenocarcinoma of the lower two-thirds of the rectum. The radiation dose was 50 Gy over 5 weeks (46 Gy to whole pelvis + 4 Gy boost), and capecitabine was administered daily at a dose of 1650 mg/m(2) during the entire course of radiation therapy. Surgery was performed with standardized total mesorectal excision 4 to 6 weeks after completion of CRT and followed by four cycles of capecitabine (2500 mg/m(2)/day for 14 days).


RESULTS
Ninety-five patients were entered into this study; their median age was 55 (range, 31-75 years). Ninety (95%) patients completed preoperative CRT as planned, and complete resection was achieved in 92 of 94 resected cases (98%). Downstaging rate was 71% (56/79) on endorectal ultrasonography, and it was 76% (71/94) on pathology finding. No tumor cell was observed in the specimens of 11 patients (12%). Among the 54 whose tumor was located within 5 cm from the anal verge, 40 patients (74%) underwent sphincter-preserving procedures. Elevation of the distal tumor margin from the anal verge by preoperative CRT was 0.8 +/- 1.3 cm. Grade 3 toxicities were rare (diarrhea in 3% and neutropenia in 1%).


CONCLUSIONS
Preoperative CRT using capecitabine achieved encouraging rates of tumor downstaging and sphincter preservation with a low toxicity profile.
Kim
Jin Cheon
JC
Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap-Dong, Songpa-Gu, Seoul 138-736, South Korea.
Kim
Tae Won
TW
Kim
Jong Hoon
JH
Yu
Chang Sik
CS
Kim
Hee Cheol
HC
Chang
Heung Moon
HM
Ryu
Min Hee
MH
Park
Jin Hong
JH
Ahn
Seung Do
SD
Lee
Sang-Wook
SW
Shin
Seong Soo
SS
Kim
Jung Sun
JS
Choi
Eun Kyung
EK
D000293:Adolescent; D000328:Adult; D000368:Aged; D000069287:Capecitabine; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects / Q000627:therapeutic use*; D011878:Radiotherapy; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*
D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil