Preoperative capecitabine and accelerated intensity-modulated radiotherapy in locally advanced rectal cancer: a phase II trial.
OBJECTIVE
A prospective phase II trial was conducted to evaluate the feasibility, safety, and pathologic response rate of preoperative capecitabine and accelerated synchronous integrated boost (SIB) intensity-modulated radiotherapy (IMRT) in patients with locally advanced rectal cancer.


METHODS
Consenting operable patients with stage II or III adenocarcinoma of the rectum received capecitabine (825 mg/m2 PO BID, 5 days/wk x 5 weeks) and SIB-IMRT delivering 55 Gy (2.2 Gy/fraction) to the gross tumor while simultaneously delivering 45 Gy (1.8 Gy/fraction) to the regional lymph nodes and areas at risk for harboring microscopic disease. Total mesorectal excision followed 6 weeks later. A single pathologist analyzed the resected tumor's TNM stage and Mandard regression/response scores. The primary end point was pathologic complete response (pCR) rate.


RESULTS
Ten subjects were enrolled, 2 of which were ineligible (1 screening failure and 1 unrelated cerebrovascular accident occurring early in treatment). The remaining 8 patients were evaluable. All 8 completed chemoradiation with strict compliance to the protocol schedule and then went on to surgical resection. At a median follow-up of 26 months (range, 15-40), all patients were alive without evidence of recurrent disease. The crude pCR rate was 38% with 50% achieving down-staging. Of 3 patients who had tumors within 5 cm of the anal verge, 2 underwent sphincter-sparing procedures. Grade 4 diarrhea occurred in 1 of 8 (13%) patients. The remaining toxicities were grade 1 or 2.


CONCLUSIONS
Preoperative chemoradiation with capecitabine and SIB-IMRT is well tolerated and results in an encouraging pCR rate for patients with locally advanced rectal cancer.
Ballonoff
Ari
A
Department of Radiation Oncology, University of Colorado Health Sciences Center, Aurora, CO 80045-0508, USA. ari.ballonoff@uchsc.edu
Kavanagh
Brian
B
McCarter
Martin
M
Kane
Madeleine
M
Pearlman
Nathan
N
Nash
Russell
R
Shah
Raj J
RJ
Raben
David
D
Schefter
Tracey E
TE
D000230:Adenocarcinoma / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000069287:Capecitabine; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D005240:Feasibility Studies; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011292:Premedication; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D050397:Radiotherapy, Intensity-Modulated; D012004:Rectal Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D012074:Remission Induction
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil