title: Phase II study of concomitant chemoradiotherapy with local hyperthermia and metronidazole for locally advanced fixed rectal cancer.
abstract: OBJECTIVE
  Locally advanced fixed T4 rectal cancer has a poor prognosis and no standard treatment strategy. The aim of this study was to investigate the safety and efficacy of neoadjuvant chemoradiotherapy using hypofractionated radiotherapy combined with local hyperthermia, capecitabine, oxaliplatin and metronidazole.
  
  
  METHODS
  Radiotherapy was given to a total dose of 40 Gy in 10 fractions. Capecitabine 650 mg/m(2) twice a day was given on days 1-22 and intravenous oxaliplatin 50 mg/m(2) was administered on days 3, 10 and 17. Local hyperthermia, 41-45°C for 60 min, was performed on days 8, 10, 15 and 17. Metronidazole 10 g/m(2) was administered per rectum on days 8 and 15. Surgery was carried out within 6-8 weeks after neoadjuvant treatment. The primary end-point was R0 resection rate. Secondary end-points included 2-year disease-free survival, 2-year overall survival, local recurrence rate, grade III-IV tumour regression (Dworak) and treatment toxicity.
  
  
  RESULTS
  From July 2006 to February 2011, 64 previously untreated patients were enrolled. R0 resection was carried out in 59 (92.2%). Five (7.8%) remained inoperable. Seven (10.9%) patients had grade IV and 30 (46.9%) had grade III regression. The main grade III toxic events included diarrhoea (15.6%, n = 10), vomiting (3.1%, n = 2), proctitis (3.1%, n = 2) and skin reaction (1.6%, n = 1). Only one (1.6%) patient had grade IV diarrhoea and vomiting. The median follow-up was 24.9 months. Two-year overall survival was 91% and 2-year disease-free survival was 83%.
  
  
  CONCLUSIONS
  Hyperthermia combined with chemotherapy to produce radiosensitization for locally advanced fixed primary rectal cancer is followed by a high R0 resection rate, with toxicity comparable with standard regimens.
authors.affiliation: Department of Oncoproctology, Russian N. N. Blokhin Cancer Research Center, Moscow, Russia.
authors.forename: Yu A
authors.initials: YA
authors.lastname: Barsukov
authors.forename: S S
authors.initials: SS
authors.lastname: Gordeyev
authors.forename: S I
authors.initials: SI
authors.lastname: Tkachev
authors.forename: M Yu
authors.initials: MY
authors.lastname: Fedyanin
authors.forename: A G
authors.initials: AG
authors.lastname: Perevoshikov
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D059248:Chemoradiotherapy / Q000379:methods*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use*; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D009944:Organoplatinum Compounds; D011838:Radiation-Sensitizing Agents; D000077150:Oxaliplatin; D003841:Deoxycytidine; D008795:Metronidazole; D000069287:Capecitabine; D005472:Fluorouracil
keywords: Fixed rectal cancer; chemoradiotherapy; hyperthermia; metronidazole