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.
Department of Radiation Oncology, University of Colorado Health Sciences Center, Aurora, CO 80045-0508, USA. ari.ballonoff@uchsc.edu
Ari
A
Ballonoff
Brian
B
Kavanagh
Martin
M
McCarter
Madeleine
M
Kane
Nathan
N
Pearlman
Russell
R
Nash
Raj J
RJ
Shah
David
D
Raben
Tracey E
TE
Schefter
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