title: Raltitrexed and radiotherapy as adjuvant treatment for stage II-III rectal cancer: a feasibility study.
abstract: OBJECTIVE
  Adjuvant 5-FU chemotherapy plus radiotherapy represents the standard treatment for radically resected rectal cancer at high risk of relapse according to the NIH Consensus Conference. The therapeutic gain was obtained with a high rate of severe treatment-related toxicity and a suboptimal patient compliance with this regimen. Raltitrexed is a specific thymidylate synthase inhibitor with a convenient administration schedule, acceptable toxicity and radiosensitizing properties, as the published phase I trials in combination with radiotherapy have shown. The aim of this prospective multicenter phase II study was to evaluate the feasibility, gastrointestinal and hematological acute toxicity of raltitrexed in combination with radiotherapy in rectal cancer patients.
  
  
  METHODS
  From September 2000 to June 2004, 50 patients with radically resected stage II-III rectal adenocarcinoma were treated. All patients were evaluable for compliance and acute toxicity. Within 45-60 days of surgery, each patient underwent concomitant adjuvant radiochemotherapy. Radiotherapy was administered to the pelvis (plus perineum after abdominoperineal resection) with photon beam energy exceeding 5 MV, 3-4 fields, 45 Gy/25 fractions/5 weeks plus a boost delivered to the site of resected disease with 3-4 fields, 9 Gy/5 fractions/1 week to a total dose of 54 Gy. The boost dose was administered after complete exclusion of the small bowel from the treatment volumes; if this was not possible a total dose of 50.4 Gy was given. Raltitrexed was administered intravenously at a dose of 3 mg/m2 as a bolus injection on days 1 and 22 of radiotherapy one hour before treatment, for a total of two cycles. Each patient underwent weekly clinical evaluation and laboratory tests. Toxicity was assessed by the WHO scale.
  
  
  RESULTS
  Forty-five (90%) patients completed the established treatment. Acute severe toxicity included grade III proctitis in 4/50 (8%), grade III-IV diarrhea in 4/50 (8%), grade III perineal dermatitis in 4/50 (8%) and grade III leukopenia in 2/50 (4%) patients; five patients (10%) experienced a transient grade Ill increase in their liver biochemistry values.
  
  
  CONCLUSIONS
  Our data related to acute toxicity and patient compliance proved the feasibility of this adjuvant radiochemotherapy treatment. A longer follow-up is necessary to evaluate the effectiveness of this new regimen in terms of disease-free and overall survival.
authors.affiliation: Radiation Oncology Center, Policlinico Monteluce, Via B. Brunamonti, 06125 Perugia, Italy. kiralupis@libero.it
authors.forename: Marco
authors.initials: M
authors.lastname: Lupattelli
authors.forename: Ernesto
authors.initials: E
authors.lastname: Maranzano
authors.forename: Rita
authors.initials: R
authors.lastname: Bellavita
authors.forename: Giovanni
authors.initials: G
authors.lastname: Natalini
authors.forename: Enrichetta
authors.initials: E
authors.lastname: Corgna
authors.forename: Riccardo
authors.initials: R
authors.lastname: Rossetti
authors.forename: Fabio
authors.initials: F
authors.lastname: Trippa
authors.forename: Francesca
authors.initials: F
authors.lastname: Mascioni
authors.forename: Angelo
authors.initials: A
authors.lastname: Sidoni
authors.forename: Paola
authors.initials: P
authors.lastname: Anselmo
authors.forename: Franco
authors.initials: F
authors.lastname: Buzzi
authors.forename: Mauro
authors.initials: M
authors.lastname: Brugia
authors.forename: Paolo
authors.initials: P
authors.lastname: Latini
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010349:Patient Compliance; D011446:Prospective Studies; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D004791:Enzyme Inhibitors; D011799:Quinazolines; D013876:Thiophenes; D013940:Thymidylate Synthase; C068874:raltitrexed