title: Preoperative treatment with capecitabine, bevacizumab and radiotherapy for primary locally advanced rectal cancer--a two stage phase II clinical trial.
abstract: OBJECTIVE
  The aim of this single-arm multicenter phase II clinical trial was to assess the feasibility and tolerability of preoperative radiotherapy and simultaneous capecitabine and bevacizumab. Secondary endpoints were downstaging-rate and induction of complete pathological response.
  
  
  METHODS
  Patients with cT3 rectal cancer were eligible. Capecitabine (825 mg/sqm twice daily on radiotherapy-days weeks 1-4) and bevacizumab (5 mg/kg on days 1, 15 and 29) were administered concurrently to pelvic radiotherapy (1.8 Gy daily up to 45 Gy in 5 weeks). Surgery followed 6-8 weeks later. A two-stage trial was designed with early termination at eight patients if more than three patients had experienced a common toxicity criteria ≥grade 3 according to the NCI CTC guidelines.
  
  
  RESULTS
  In the first stage eight patients were enrolled. Median age was 70 years (range 55-76) and ECOG PS 0/1 (%) was 87.5/12.5. Major side effects were mostly intestinal bleeding (grade 3, 25%), diarrhea (grade 3, 25%), perianal and abdominal pain (grades 3 and 4, 25%) followed by anemia (grade 3, 12.5%). Tumor downstaging was observed in 37.5% of patients with complete pathological response in two patients (25%).
  
  
  CONCLUSIONS
  After interim analysis of feasibility and tolerability, accrual was terminated according to protocol due to ≥grade 3 toxicities in 50% of patients. Complete pathological response was seen in 25% of patients but was accompanied by considerable toxicity. Further clinical trials are needed to clarify the role of bevacizumab in this setting.
authors: Department of Internal Medicine IV, Klinikum Wels-Grieskirchen, Austria. gudrun.resch@klinikum-wegr.at
authors: Gudrun
authors: G
authors: Resch
authors: Alexander
authors: A
authors: De Vries
authors: Dietmar
authors: D
authors: Öfner
authors: Wolfgang
authors: W
authors: Eisterer
authors: Hans
authors: H
authors: Rabl
authors: Michael
authors: M
authors: Jagoditsch
authors: Michael
authors: M
authors: Gnant
authors: Josef
authors: J
authors: Thaler
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D000069287:Capecitabine; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D005472:Fluorouracil