title: Raltitrexed (Tomudex) administration in patients with relapsed metastatic colorectal cancer after weekly irinotecan/5-Fluorouracil/Leucovorin chemotherapy.
abstract: OBJECTIVE
  The present study aimed at evaluating the efficacy of Raltitrexed, a specific thymidilate synthase inhibitor, in patients with advanced colorectal cancer (ACC) in relapse (>8 weeks) after a prior response or disease stabilization to first-line chemotherapy combination with lrinotecan+5-Fluorouracil (5-FU)+Leucovorin (LV).
  
  
  METHODS
  Twenty-five patients with metastatic ACC entered; 17 males/8 females, median age 61 (range: 47-70), median Karnovsky PS: 80 (70-90), and sites of metastases; liver: 21, lung: 4, lymph nodes: 7, peritoneal: 5 and a life expectancy of at least 3 months, were entered in the present pilot study. All patients had progressed after prior chemotherapy with lrinotecan+5-FU+LV. Raltitrexed was administered at a dose of 3 mg/m2 i.v. every 21 days.
  
  
  RESULTS
  Three patients (12%) achieved a partial response (PR), 8 (32%) had stable disease (SD), and the remaining 14 (56%) developed progressive disease (PD). Median time-to-progression (TTP) was 5.5 months (range, 2-8.5), and median overall survival (OS) 8 months (range, 4.0-12.5). Toxicity was generally mild; it consisted mainly of myelosuppression; neutropenia grade 1-2: 52%-grade 3: 28%, and anemia grade 1-2 only: 36%. Mild mucositis grade 1-2 occurred in 13.5% of patients and was the principal non-hematologic toxicity.
  
  
  CONCLUSIONS
  Response to treatment with Raltitrexed is limited in patients with ACC failing after an initial response or non-progression to the weekly lrinotecan+5-FU+LV combination. However, it appears that a limited number of patients with PR/SD may derive clinical benefit, but final proof would require a randomized study.
authors.affiliation: Medical Oncology Unit, Department of Pathophysiology, Laikon General Hospital, Athens University School of Medicine, Athens, Greece. tsavari1@otenet.gr
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tsavaris
authors.forename: Christos
authors.initials: C
authors.lastname: Kosmas
authors.forename: Maria
authors.initials: M
authors.lastname: Vadiaka
authors.forename: Christos
authors.initials: C
authors.lastname: Koufos
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary*; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000556:secondary*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary*; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000556:secondary*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods; D055502:Secondary Prevention; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D011799:Quinazolines; D013876:Thiophenes; D000077146:Irinotecan; C068874:raltitrexed; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin