title: Carboplatin in combination with raltitrexed in recurrent and metastatic head and neck squamous cell carcinoma: A multicentre phase II study of the Gruppo Oncologico Dell'Italia Meridionale (G.O.I.M.).
abstract: BACKGROUND
  The combination of cisplatin (CDDP) and 5-Fluorouracil (5-FU) is a standard regimen for the treatment of recurrent and metastatic head and neck squamous cell carcinoma (HNSCC). This combination shows a relevant toxicity and new chemotherapy associations with a more favourable toxicity profile are awaited. Carboplatin (CB) is a platinum derivative with less toxicity than CDDP. Raltitrexed (R) is a potent and specific thymidylate synthase inhibitor with activity comparable to that of 5-FU in colorectal cancer; moreover, it showed activity as a single agent in HNSCC.
  
  
  METHODS
  Since 2001, a multicentre, phase II trial has been underway to evaluate the efficacy and toxicity of the CB+R combination in untreated patients with recurrent or metastatic HNSCC. Thirty-two patients were enrolled and included in an intent-to-treat analysis. Toxicity was graded according to NCI criteria. Patients had a histo/cytologically proven recurrent or metastatic HNSCC; patients with locally advanced disease not amenable to CDDP+5-FU treatment were also included. Patients had to be >18 years old with ECOG PS of 0-2 and adequate bone marrow, renal and liver functions. CB (AUC 5) and R (3 mg/m2) were administered intravenously every 3 weeks. The median age was 62 years (range 43-71), 29 M/3 F. The median PS was 1 (0-2). Twelve patients were staged III and 20 were metastatic (10 recurrent). The oral cavity/oropharynx were the primary site in 20 patients and the larynx in 10 patients. The median number of cycles delivered was 3, while globally 115 cycles were administered. The median time to progression was 4.2 months and median duration of survival was 9.8 months.
  
  
  RESULTS
  Seven patients achieved a partial response (22%), 10 patients showed a stable disease (31%), while 13 patients (48%) had progressive disease. Eight patients (25%) had a G 3-4 neutropenia, while G 3-4 anaemia was observed in 2 patients and thrombocytopenia in 1 patient. No extrar haematological G 3-4 toxicities were observed. A persistent G 2 hepatic toxicity led a patient to drop out from the study.
  
  
  CONCLUSIONS
  In our phase II trial, CB in combination with R showed a moderate activity with safe administration on an outpatient basis.
authors.affiliation: Medical and Experimental Department, Oncology Institute of Bari, Via Hanhemann 10, 70126 Bari, Italy. galetta@teseo.it
authors.forename: Domenico
authors.initials: D
authors.lastname: Galetta
authors.forename: Francesco
authors.initials: F
authors.lastname: Giotta
authors.forename: Gerardo
authors.initials: G
authors.lastname: Rosati
authors.forename: Vittorio
authors.initials: V
authors.lastname: Gebbia
authors.forename: Luigi
authors.initials: L
authors.lastname: Manzione
authors.forename: Maurizio
authors.initials: M
authors.lastname: Di Bisceglie
authors.forename: Nicola
authors.initials: N
authors.lastname: Borsellino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Colucci
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D015996:Survival Rate; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D011799:Quinazolines; D013876:Thiophenes; D016190:Carboplatin; C068874:raltitrexed