title: Preoperative chemoradiation with cetuximab, irinotecan, and capecitabine in patients with locally advanced resectable rectal cancer: a multicenter Phase II study.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of preoperative chemoradiation with cetuximab, irinotecan, and capecitabine in patients with rectal cancer.
  
  
  METHODS
  Forty patients with locally advanced, nonmetastatic, and mid- to lower rectal cancer were enrolled. Radiotherapy was delivered at a dose of 50.4 Gy/28 fractions. Concurrent chemotherapy consisted of an initial dose of cetuximab of 400 mg/m(2) 1 week before radiotherapy, and then cetuximab 250 mg/m(2)/week, irinotecan 40 mg/m(2)/week for 5 consecutive weeks and capecitabine 1,650 mg/m(2)/day for 5 days a week (weekdays only) from the first day during radiotherapy. Total mesorectal excision was performed within 6 ± 2 weeks. The pathologic responses and survival outcomes were evaluated as study endpoints, and an additional KRAS mutation analysis was performed.
  
  
  RESULTS
  In total, 39 patients completed their planned preoperative chemoradiation and underwent R0 resection. The pathologic complete response rate was 23.1% (9/39), and 3 patients (7.7%) showed near total regression of tumor. The 3-year disease-free and overall survival rates were 80.0% and 94.7%, respectively. Grade 3/4 toxicities included leukopenia (4, 10.3%), neutropenia (2, 5.1%), anemia (1, 2.6%), diarrhea (2, 5.1%), fatigue (1, 2.6%), skin rash (1, 2.6%), and ileus (1, 2.6%). KRAS mutations were found in 5 (13.2%) of 38 patients who had available tissue for testing. Clinical outcomes were not significantly correlated with KRAS mutation status.
  
  
  CONCLUSIONS
  Preoperative chemoradiation with cetuximab, irinotecan, and capecitabine was active and well tolerated. KRAS mutation status was not a predictive factor for pathologic response in this study.
authors.affiliation: Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Yong Sang
authors.initials: YS
authors.lastname: Hong
authors.forename: Dae Yong
authors.initials: DY
authors.lastname: Kim
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Kim
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Seok Ah
authors.initials: SA
authors.lastname: Im
authors.forename: Keun Seok
authors.initials: KS
authors.lastname: Lee
authors.forename: Tak
authors.initials: T
authors.lastname: Yun
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Jeong
authors.forename: Hyo Seong
authors.initials: HS
authors.lastname: Choi
authors.forename: Seok-Byung
authors.initials: SB
authors.lastname: Lim
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Chang
authors.forename: Kyung Hae
authors.initials: KH
authors.lastname: Jung
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D000068818:Cetuximab; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D009367:Neoplasm Staging; D011300:Preoperative Care / Q000379:methods; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D012074:Remission Induction / Q000379:methods; D018631:ras Proteins / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D005472:Fluorouracil; D002166:Camptothecin