title: Phase II study of pemetrexed in combination with cisplatin and cetuximab in recurrent or metastatic squamous cell carcinoma of the head and neck.
abstract: OBJECTIVE
  Platinum/5-fluorouracil plus cetuximab is a standard systemic treatment for recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Pemetrexed has shown activity in SCCHN. This phase II study evaluated pemetrexed with cisplatin and cetuximab in recurrent/metastatic SCCHN.
  
  
  METHODS
  Patients received cetuximab 250 mg/m(2) (loading dose: 400mg/m(2))days 1, 8 and 15; pemetrexed 500 mg/m(2)+cisplatin 75 mg/m(2) on day 1, q3w up to six cycles and folic acid, vitamin B12 and prophylactic medications. After a minimum of four cycles, responding patients were eligible for maintenance with pemetrexed and cetuximab, or either as monotherapy, until progression or toxicity. Efficacy (primary end-point: progression-free survival [PFS]) and toxicity were evaluated.
  
  
  RESULTS
  Sixty-six patients received ≥1 cycle of the triplet. Most patients were male (80.3%), with a median age of 62 years and Eastern Cooperative Oncology Group (ECOG) performance status of 1 (71.2%). Diagnoses included oropharynx (45.5%) and larynx (24.2%) cancers, with locoregional disease (51.5%) alone, or combined with distant metastases (48.5%). Median (m) PFS was 4.4 months (95% confidence interval [CI]: 3.6, 5.4); median overall survival was 9.7 months (95% CI: 6.5, 13.1). Objective response rate was 29.3%; 23 patients had stable disease (39.7%). Drug-related grade 3/4 toxicities included neutropaenia (33.3%), fatigue (24.2%), anorexia (12.1%) and infection (10.6%). Five treatment-related deaths (7.6%) occurred.
  
  
  CONCLUSIONS
  Efficacy results were consistent with current standard treatment for this patient population, but the pre-specified mPFS of 5.5 months was not achieved. Grade 3/4 toxicities were also consistent with standard treatment, although treatment-related deaths were higher than expected.
authors.affiliation: Antwerp University Hospital, Edegem, Belgium. Jan.B.Vermorken@uza.be.
authors.forename: J B
authors.initials: JB
authors.lastname: Vermorken
authors.forename: L
authors.initials: L
authors.lastname: Licitra
authors.forename: J
authors.initials: J
authors.lastname: Stöhlmacher-Williams
authors.forename: A
authors.initials: A
authors.lastname: Dietz
authors.forename: J M
authors.initials: JM
authors.lastname: Lopez-Picazo
authors.forename: O
authors.initials: O
authors.lastname: Hamid
authors.forename: A M
authors.initials: AM
authors.lastname: Hossain
authors.forename: S-C
authors.initials: SC
authors.lastname: Chang
authors.forename: T C
authors.initials: TC
authors.lastname: Gauler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000068818:Cetuximab; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005060:Europe; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D000068437:Pemetrexed; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D000068818:Cetuximab; D002945:Cisplatin
keywords: Cetuximab; Cisplatin; Head and neck squamous cell carcinoma; Pemetrexed