title: Oxaliplatin plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy for locally advanced rectal carcinoma: long-term outcome.
abstract: OBJECTIVE
  To assess the safety and efficacy of oxaliplatin (OXA) plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy (RT) in patients with poor prognosis for rectal carcinoma.
  
  
  METHODS
  Sixty-three patients with the following characteristics, a clinical (c) stage T4, cN1-2, or cT3N0 of ≤5 cm from the anal verge and/or with a circumferential resection margin (CRM) of ≤5 mm (by magnetic resonance imaging), received three biweekly courses of chemotherapy with OXA, 100 mg/m2; raltitrexed (RTX), 2.5 mg/m2 on day 1, and 5-fluorouracil (5-FU), 900 mg/m2 (31 patients) or 800 mg/m2 (32 patients); levo-folinic acid (LFA), 250 mg/m2 on day 2, during pelvic RT (45 Gy). Pathologic response was defined as complete pathological response (ypCR), major (tumor regression grade(TRG) 2 to 3, with ypCRM-ve and ypN-ve) or minor or no response (TRG4 to -5, or ypCRM+ve, or ypN+ve). Adjuvant 5-FU/LFA regimen was given in cases of cT4, ypN+ve, or ypCRM+ve.
  
  
  RESULTS
  Overall, neutropenia (40%) and diarrhea (13%) were the most common grade≥3 toxicities, and tolerability was better with a 5-FU dose reduction. No significant difference in pathologic response was seen according 5-FU dosage: overall, a ypCR was obtained in 24 (39%) patients, and a major response in 20 (32%) patients. The 5-year probability of freedom from recurrence was 80% (95% confidence interval, 68%-92%); it was 56% for the minor/no response group, while it was around 90% for both the ypCR and the major response group.
  
  
  CONCLUSIONS
  OXA, RTX, and 5-FU/LFA administered during pelvic RT produced promising early and long-term results in rectal carcinoma patients with poor prognosis. The postoperative treatment strategy applied in our study supports the risk-adapted approach in postoperative management.
authors.affiliation: Department of Gastrointestinal Medical Oncology, National Cancer Institute, Naples, Italy. avalloneantonio@libero.it
authors.forename: Antonio
authors.initials: A
authors.lastname: Avallone
authors.forename: Paolo
authors.initials: P
authors.lastname: Delrio
authors.forename: Biagio
authors.initials: B
authors.lastname: Pecori
authors.forename: Fabiana
authors.initials: F
authors.lastname: Tatangelo
authors.forename: Antonella
authors.initials: A
authors.lastname: Petrillo
authors.forename: Nigel
authors.initials: N
authors.lastname: Scott
authors.forename: Pietro
authors.initials: P
authors.lastname: Marone
authors.forename: Luigi
authors.initials: L
authors.lastname: Aloi
authors.forename: Claudia
authors.initials: C
authors.lastname: Sandomenico
authors.forename: Secondo
authors.initials: S
authors.lastname: Lastoria
authors.forename: Vincenzo Rosario
authors.initials: VR
authors.lastname: Iaffaioli
authors.forename: Dario
authors.initials: D
authors.lastname: Scala
authors.forename: Giovanni
authors.initials: G
authors.lastname: Iodice
authors.forename: Alfredo
authors.initials: A
authors.lastname: Budillon
authors.forename: Pasquale
authors.initials: P
authors.lastname: Comella
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D003967:Diarrhea / Q000209:etiology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D009367:Neoplasm Staging; D009503:Neutropenia / Q000209:etiology; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D000077150:Oxaliplatin; D011183:Postoperative Complications / Q000473:pathology; D011300:Preoperative Care / Q000379:methods; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D012074:Remission Induction / Q000379:methods; D013876:Thiophenes / Q000008:administration & dosage; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome; D014803:Vitamin B Complex / Q000008:administration & dosage
chemical_list: D009363:Neoplasm Proteins; D009944:Organoplatinum Compounds; D011799:Quinazolines; D013876:Thiophenes; D000077150:Oxaliplatin; D014803:Vitamin B Complex; D013940:Thymidylate Synthase; C068874:raltitrexed; D002955:Leucovorin; D005472:Fluorouracil