title: Unexpected toxicity of cetuximab combined with conventional chemoradiotherapy in patients with locally advanced anal cancer: results of the UNICANCER ACCORD 16 phase II trial.
abstract: BACKGROUND
  The ACCORD 16 phase II trial aimed to evaluate the objective response rate after combination of conventional chemoradiotherapy (CRT) and cetuximab in locally advanced anal canal carcinoma (LAACC).
  
  
  METHODS
  Immunocompetent patients with histologically confirmed LAACC received CRT [45 gray (Gy)] in 25 fractions over 5 weeks, fluorouracil and cisplatin during weeks 1 and 5), in combination with weekly dose of cetuximab (250 mg/m(2) with a loading dose of 400 mg/m(2) 1 week before irradiation), and a standard dose boost (20 Gy). The trial was originally designed to include 81 patients to detect a 15% of objective response increase with the new combination in comparison with CRT.
  
  
  RESULTS
  The trial was prematurely stopped after the declaration of 15 serious adverse events (SAEs) in 14 out of 16 patients. Five patients received the entire planned treatment, and the compliance was higher after amendments of the protocol. Among the 15 SAEs, 6 were unexpected. Grade (G) 3/4 acute toxic effects, observed in 88% patients, were general (n = 13, 81%), digestive (n = 9, 56%), dermatological (n = 5, 31%), infectious (n = 4, 25%), haematological (n = 3, 19%), and others (n = 9); and three patients suffered from six G3/4 late toxic effects. No treatment-related death was reported. All 11 assessable patients had an objective response consisting of six complete (55%) and five partial (45%) response 2 months after the end of the treatment. Thirteen patients were followed up with a median of 22 months [95% confidence interval (CI ): 18-27] and had a 1-year colostomy-free survival, progression-free and overall survival rate of 67% (95% CI: 40%-86%), 62% (95% CI: 36%-82%), and 92% (95% CI: 67%-99%), respectively.
  
  
  CONCLUSIONS
  CRT plus cetuximab was unacceptably toxic in this population of patients. Results of others phase II trials evaluating this combination are awaited to confirm these findings.
  2007-007029-38.
authors.affiliation: Department of Radiotherapy, Institut Gustave-Roussy, Villejuif.
authors.forename: E
authors.initials: E
authors.lastname: Deutsch
authors.forename: C
authors.initials: C
authors.lastname: Lemanski
authors.forename: J P
authors.initials: JP
authors.lastname: Pignon
authors.forename: A
authors.initials: A
authors.lastname: Levy
authors.forename: A
authors.initials: A
authors.lastname: Delarochefordiere
authors.forename: I
authors.initials: I
authors.lastname: Martel-Lafay
authors.forename: E
authors.initials: E
authors.lastname: Rio
authors.forename: D
authors.initials: D
authors.lastname: Malka
authors.forename: T
authors.initials: T
authors.lastname: Conroy
authors.forename: L
authors.initials: L
authors.lastname: Miglianico
authors.forename: Y
authors.initials: Y
authors.lastname: Becouarn
authors.forename: K
authors.initials: K
authors.lastname: Malekzadeh
authors.forename: E
authors.initials: E
authors.lastname: Paris
authors.forename: B
authors.initials: B
authors.lastname: Juzyna
authors.forename: P
authors.initials: P
authors.lastname: Ezra
authors.forename: D
authors.initials: D
authors.lastname: Azria
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D000068818:Cetuximab; D059248:Chemoradiotherapy / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D064420:Drug-Related Side Effects and Adverse Reactions / Q000145:classification / Q000473:pathology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D011878:Radiotherapy / Q000009:adverse effects
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab; D002945:Cisplatin; D005472:Fluorouracil
keywords: anal cancer; cetuximab; chemoradiotherapy; phase II; targeted therapy; toxicity