title: Preoperative radiation therapy with concurrent capecitabine, bevacizumab, and erlotinib for rectal cancer: a phase 1 trial.
abstract: OBJECTIVE
  The goal of this phase 1 trial was to determine the maximum tolerated dose (MTD) of concurrent capecitabine, bevacizumab, and erlotinib with preoperative radiation therapy for rectal cancer.
  
  
  METHODS
  Patients with clinical stage II to III rectal adenocarcinoma, within 12 cm from the anal verge, were treated in 4 escalating dose levels, using the continual reassessment method. Patients received preoperative radiation therapy with concurrent bevacizumab (5 mg/kg intravenously every 2 weeks), erlotinib, and capecitabine. Capecitabine dose was increased from 650 mg/m(2) to 825 mg/m(2) orally twice daily on the days of radiation therapy; erlotinib dose was increased from 50 mg orally daily in weeks 1 to 3, to 50 mg daily in weeks 1 to 6, to 100 mg daily in weeks 1 to 6. Patients underwent surgery at least 9 weeks after the last dose of bevacizumab.
  
  
  RESULTS
  A total of 19 patients were enrolled, and 18 patients were considered evaluable. No patient had grade 4 acute toxicity, and 1 patient had grade 3 acute toxicity (hypertension). The MTD was not reached. All 18 evaluable patients underwent surgery, with low anterior resection in 7 (39%), proctectomy with coloanal anastomosis in 4 patients (22%), posterior pelvic exenteration in 1 (6%), and abdominoperineal resection in 6 (33%). Of the 18 patients, 8 (44%) had pathologic complete response, and 1 had complete response of the primary tumor with positive nodes. Three patients (17%) had grade 3 postoperative complications (ileus, small bowel obstruction, and infection). With a median follow-up of 34 months, 1 patient developed distant metastasis, and no patient had local recurrence or died. The 3-year disease-free survival was 94%.
  
  
  CONCLUSIONS
  The combination of preoperative radiation therapy with concurrent capecitabine, bevacizumab, and erlotinib was well tolerated. The pathologic complete response rate appears promising and may warrant further investigation.
authors: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: PrajDas@mdanderson.org.
authors: Prajnan
authors: P
authors: Das
authors: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Cathy
authors: C
authors: Eng
authors: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Miguel A
authors: MA
authors: Rodriguez-Bigas
authors: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: George J
authors: GJ
authors: Chang
authors: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: John M
authors: JM
authors: Skibber
authors: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Y Nancy
authors: YN
authors: You
authors: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Dipen M
authors: DM
authors: Maru
authors: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Mark F
authors: MF
authors: Munsell
authors: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Marilyn V
authors: MV
authors: Clemons
authors: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Scott E
authors: SE
authors: Kopetz
authors: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Christopher R
authors: CR
authors: Garrett
authors: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Imad
authors: I
authors: Shureiqi
authors: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Marc E
authors: ME
authors: Delclos
authors: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Sunil
authors: S
authors: Krishnan
authors: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Christopher H
authors: CH
authors: Crane
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D000069287:Capecitabine; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D057239:Early Termination of Clinical Trials / Q000191:economics; D000069347:Erlotinib Hydrochloride; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011300:Preoperative Care; D011799:Quinazolines / Q000008:administration & dosage; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D011799:Quinazolines; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D000069347:Erlotinib Hydrochloride; D005472:Fluorouracil