title: Preoperative capecitabine with pelvic radiotherapy for locally advanced rectal cancer (phase I trial).
abstract: OBJECTIVE
  Phase I multicenter study defined the maximal tolerated dose (MTD), dose-limiting toxicity (DLT) and safety profile of capecitabine in combination with preoperative radiation for patients with locally advanced rectal cancer (LARC).
  
  
  METHODS
  Patients were treated with oral capecitabine (700, 800, 900, 1000, 1100 and 1200 mg/m2 twice daily continuously) plus preoperative whole pelvic irradiation (45-46 Gy in 23-25 fractions over 5-6 weeks). Surgery was performed at the median of 42 days after chemoradiation treatment.
  
  
  RESULTS
  Twenty-seven patients were in this trial. Eighteen patients (3 per dose level) had received capecitabine from 700 mg/m2 twice daily to the highest dose level of 1200 mg/m2 twice daily. There were no grade 3/4 DLTs during dose escalation, a further nine patients were included at the highest capecitabine dose. Two of the twelve patients (16%) receiving capecitabine 1200 mg/m2 twice daily developed grade 3 diarrhea and discontinued treatment. There were no other grade 3/4 adverse events. After capecitabine chemoradiation, 24 of 27 patients (89%) received definite surgery. Primary and lymph node down staging occurred in ten patients (42%). Sphincter-sparing surgery was performed in seven patients (26%) and abdominal-perineal resection was performed in 17 patients (63%).
  
  
  CONCLUSIONS
  Preoperative capecitabine chemoradiation based on continuous daily capecitabine is very well tolerated in patients with LARC. The authors did not reach the MTD in the present study.
authors.affiliation: Radiation Oncology, Department of Radiology, Siriraj Hospital, Faculty of Medicine, Mahidol University, 2 Prannok Rd, Bangkoknoi, Bangkok 10700, Thailand. vutisiri@hotmail.com
authors.forename: Vutisiri
authors.initials: V
authors.lastname: Veerasarn
authors.forename: Pramook
authors.initials: P
authors.lastname: Phromratanapongse
authors.forename: Vicharn
authors.initials: V
authors.lastname: Lorvidhaya
authors.forename: Prasert
authors.initials: P
authors.lastname: Lertsanguansinchai
authors.forename: Chawalit
authors.initials: C
authors.lastname: Lertbutsayanukul
authors.forename: Apichart
authors.initials: A
authors.lastname: Panichevaluk
authors.forename: Wiroon
authors.initials: W
authors.lastname: Boonnuch
authors.forename: Vitoon
authors.initials: V
authors.lastname: Chinswangwatanakul
authors.forename: Darin
authors.initials: D
authors.lastname: Lohsiriwat
authors.forename: Arun
authors.initials: A
authors.lastname: Rojanasakul
authors.forename: Parinya
authors.initials: P
authors.lastname: Thavichaigarn
authors.forename: Paiboon
authors.initials: P
authors.lastname: Jivapaisarnpong
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D000069287:Capecitabine; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil