title: Prospective phase II trial of nimotuzumab in combination with radiotherapy and concurrent capecitabine in locally advanced rectal cancer.
abstract: OBJECTIVE
  The aim of the study was to evaluate the safety and efficacy of adding concurrent nimotuzumab to preoperative radiotherapy with concurrent capecitabine in locally advanced rectal cancer.
  
  
  METHODS
  Patients with rectal cancer (clinical stage T3/4 or N+) were scheduled to receive weekly nimotuzumab (400 mg; days -6, 1, 8, 15, 22, and 29). Capecitabine (825 mg/m(2)) was delivered orally twice daily for the duration of radiotherapy. Radiotherapy was administered at 50.4 Gy (45 + 5.4 Gy). The main endpoint was the pathologic complete response (pCR) rate.
  
  
  RESULTS
  Twenty-one patients with T3 or T4 disease were enrolled; 66.7 % were nodal-positive; the median distance from the anal verge was 5.5 cm. A pCR was achieved in four patients (19.0 %); 71.4 % patients obtained moderate or good tumor regression (Grade 2 and 3). Downstaging occurred in 15/21 (71.4 %) patients by T stage and 11/14 (78.6 %) by N stage. The actual dose intensities (median/mean, %) were nimotuzumab (100, 100) and capecitabine (100, 99.5). The most frequent Grade 1/2 toxicities were radiation dermatitis (57.1 %), nausea/vomiting (52.4 %), leukocytopenia (47.6 %), diarrhea (47.6 %), and proctitis (38.1 %). Grade 3 diarrhea was observed in 9.5 % of patients and Grade 3 leukocytopenia in 4.8 %.
  
  
  CONCLUSIONS
  These preliminary results indicate that nimotuzumab can be safely combined with radiotherapy plus concurrent capecitabine. The efficacy of this regimen (pCR = 19.0 %) was significantly higher than that observed in previous phase II trials of preoperative radiotherapy with concurrent capecitabine and cetuximab in rectal cancer. Further investigation of concurrent nimotuzumab with radiotherapy plus capecitabine is warranted.
authors.affiliation: Department of Radiation Oncology, Zhejiang Cancer Hospital, 38 Guang Ji Road, Hangzhou, 310022, Zhejiang, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Jin
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jia-Lin
authors.initials: JL
authors.lastname: Luo
authors.forename: Ning
authors.initials: N
authors.lastname: Zhou
authors.forename: De-Chuan
authors.initials: DC
authors.lastname: Li
authors.forename: Hai-Xin
authors.initials: HX
authors.lastname: Ju
authors.forename: Yong-Tian
authors.initials: YT
authors.lastname: Fan
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Zhu
authors.forename: Hai-Yang
authors.initials: HY
authors.lastname: Feng
authors.forename: Lu-Ying
authors.initials: LY
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D059186:Chemoradiotherapy, Adjuvant; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011300:Preoperative Care; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000069287:Capecitabine; C501466:nimotuzumab; D005472:Fluorouracil