title: Open label, multi-centre phase II study of raltitrexed ('Tomudex') in patients with inoperable squamous-cell carcinoma of head and neck.
abstract: BACKGROUND
  Raltitrexed ('Tomudex') is a folate based inhibitor of thymidylate synthase which has been registered in Europe and Australia for the treatment of advanced colorectal cancer. In a European phase I trial of raltitrexed anti-tumour activity was seen in two patients with head and neck cancer, prompting the current study.
  
  
  METHODS
  From November 1996 to December 1998, 24 patients with metastatic or recurrent squamous-cell carcinoma of the head and neck from 7 Australian centres received raltitrexed, 3 mg/m2 given intravenously over 15 minutes every 3 weeks, for a maximum of 6 cycles. Patients were required to be chemotherapy naïve and have measurable disease, age > 18 years, WHO performance status initially < or = 2, no significant intercurrent illness or organ dysfunction and a life expectancy > 12 weeks.
  
  
  RESULTS
  Twenty-two men and two women, median age 65 years, median performance status 1 were enrolled. Fifteen patients (63%) had received both prior surgery and radiotherapy. In 15 patients (63%) there was recurrent locoregional disease only. Twelve patients (50%) received one cycle of treatment with only four patients (17%) receiving four or more cycles of treatment. No patient achieved a complete or partial response, although 5 patients experienced stable disease which lasted a median of 188 days (range 61-436). The median survival for the whole group was 101 days (range 20436). Raltitrexed was generally well tolerated with minimal antiproliferative toxicity.
  
  
  CONCLUSIONS
  Single-agent raltitrexed does not demonstrate significant anti-tumour response rates in patients with predominantly locally recurrent head and neck cancer.
authors.affiliation: Sydney Cancer Centre, NSW, Australia. sclarke@canc.rpa.cs.nsw.gov.au
authors.forename: S J
authors.initials: SJ
authors.lastname: Clarke
authors.forename: J
authors.initials: J
authors.lastname: Zalcberg
authors.forename: I
authors.initials: I
authors.lastname: Olver
authors.forename: P L
authors.initials: PL
authors.lastname: Mitchell
authors.forename: D
authors.initials: D
authors.lastname: Rischin
authors.forename: D
authors.initials: D
authors.lastname: Dalley
authors.forename: M
authors.initials: M
authors.lastname: Green
authors.forename: Y E
authors.initials: YE
authors.lastname: Davidson
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D010166:Palliative Care / Q000379:methods*; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D016019:Survival Analysis; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D011799:Quinazolines; D013876:Thiophenes; C068874:raltitrexed