title: Long-term results of a phase II trial of high-dose radiotherapy (60 Gy) and UFT/l-leucovorin in patients with non-resectable locally advanced rectal cancer (LARC).
abstract: BACKGROUND
  Preoperative radiochemotherapy is a cornerstone in patients with non- resectable locally advanced rectal cancer (LARC). To improve outcome (number of R0 resections and survival) high-dose radiotherapy (RT) was combined with oral UFT/l-leucovorin to allow tumour regression before radical intended surgery.
  
  
  METHODS
  Pelvic RT was delivered with megavoltage photons using a 5 field technique. RT was CT-based, given 5 days a week through one posterior field and two lateral fields (48.6 Gy/27 fractions) to encompass the primary tumour and the regional lymph nodes. In addition, the tumour bed received a concurrent boost (5.4 Gy/27 fractions) and a final boost (6 Gy/3 fractions); thus GTV received 60 Gy/30 fractions. Concurrent with RT patients received a daily dose of oral UFT 300 mg/m(2) plus l-leucovorin 22.5 mg 5/7 days (divided in three doses).
  
  
  RESULTS
  From September 2000 to November 2004, 52 patients (median age 60 years (32-83); median PS 0 (0-2)) with LARC (36 primary, 16 recurrent) were included in this phase II study. All but three patients received the planned 60 Gy, median duration of RT was 42 days (25-49). Toxicity was very modest; only four patients had a dose reduction of UFT. No hematological toxicity of clinical significance was seen. Non-hematological toxicity grade 1 (GI-toxicity, fatigue and/or dysuria) was frequently observed but only four patients experienced grade 3 toxicity (diarrhoea and/or nausea/vomiting). Forty patients (77%) were operated (30 R0, 5 R1, 5 R2) median 55 days (27-112) after completion of RT. Seven (13%) patients had a pathological complete response (pCR). Thirty-one patients (60%) died after median 25.4 months (1.6-45.2 months). Twenty-one patients (40%) are still alive June 2007.
  
  
  CONCLUSIONS
  Preoperative high-dose RT and concomitant UFT produces major regression in most patients with non-resectable LARC and thus a good chance of cure.
authors.affiliation: Odense University Hospital, Odense, Denmark. Lene.Vestermark@ouh.regionsyddanmark.dk
authors.forename: Lene W
authors.initials: LW
authors.lastname: Vestermark
authors.forename: Anders
authors.initials: A
authors.lastname: Jacobsen
authors.forename: Camilla
authors.initials: C
authors.lastname: Qvortrup
authors.forename: Flemming
authors.initials: F
authors.lastname: Hansen
authors.forename: Claus
authors.initials: C
authors.lastname: Bisgaard
authors.forename: Gunnar
authors.initials: G
authors.lastname: Baatrup
authors.forename: Peter
authors.initials: P
authors.lastname: Rasmussen
authors.forename: Per
authors.initials: P
authors.lastname: Pfeiffer
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D019583:Dose Fractionation, Radiation; D004338:Drug Combinations; D005260:Female; D005767:Gastrointestinal Diseases / Q000209:etiology; D006402:Hematologic Diseases / Q000209:etiology; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects; D011300:Preoperative Care; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D011882:Radiotherapy, High-Energy / Q000009:adverse effects; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D016019:Survival Analysis; D005641:Tegafur / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014498:Uracil / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C096910:UFT(R) drug; D005641:Tegafur; D014498:Uracil; D002955:Leucovorin