title: EORTC 24051: unexpected side effects in a phase I study of TPF induction chemotherapy followed by chemoradiation with lapatinib, a dual EGFR/ErbB2 inhibitor, in patients with locally advanced resectable larynx and hypopharynx squamous cell carcinoma.
abstract: BACKGROUND
  In this phase I/II study, the addition of lapatinib (LAP) was investigated in combination with the sequential use of both approaches TPF induction chemotherapy (ICT) followed by chemoradiation (CRT) in locally advanced larynx or hypopharynx squamous cell carcinoma.
  
  
  METHODS
  Objectives were to assess maximum tolerated dose, dose-limiting toxicity (DLT) and to recommend a safe dose of LAP when administered with 4 cycles of TPF followed by CRT.
  
  
  RESULTS
  Seven male patients were included. Three patients were included in the first cohort, at dose level 1 (LAP 500 mg daily plus TPF). Renal toxicity was observed among these three patients (grade 3 [n=1], grade 2 [n=1] and grade 1 [n=1]), with 1 DLT, leading to treatment interruption in this group. Nephrotoxicity was reversible after stopping LAP and hydration of the patients. In a second cohort of four patients administering docetaxel from the second cycle, 3 more DLTs were observed (grade 2 renal toxicity and grade 3 diarrhea, grade 3 anorexia and grade 3 stomatitis, and grade 4 neutropenia). Based on the occurrence of 4 DLTs at the first dose level of LAP, patient recruitment was closed.
  
  
  CONCLUSIONS
  These data indicate that LAP cannot be combined safely with full dose TPF.
authors.affiliation: Institut Jules Bordet, Brussels, Belgium. yassine.lalami@bordet.be
authors.forename: Yassine
authors.initials: Y
authors.lastname: Lalami
authors.forename: Pol M
authors.initials: PM
authors.lastname: Specenier
authors.forename: Ahmad
authors.initials: A
authors.lastname: Awada
authors.forename: Denis
authors.initials: D
authors.lastname: Lacombe
authors.forename: Cecilia
authors.initials: C
authors.lastname: Liberatoscioli
authors.forename: Catherine
authors.initials: C
authors.lastname: Fortpied
authors.forename: Iman
authors.initials: I
authors.lastname: El-Hariry
authors.forename: Jan
authors.initials: J
authors.lastname: Bogaerts
authors.forename: Guy
authors.initials: G
authors.lastname: Andry
authors.forename: J A
authors.initials: JA
authors.lastname: Langendijk
authors.forename: Jan B
authors.initials: JB
authors.lastname: Vermorken
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000627:therapeutic use; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000628:therapy*; D060828:Induction Chemotherapy; D000077341:Lapatinib; D007822:Laryngeal Neoplasms / Q000628:therapy*; D008297:Male; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011799:Quinazolines / Q000009:adverse effects*; D043823:Taxoids / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D043823:Taxoids; D000077341:Lapatinib; D002945:Cisplatin; D005472:Fluorouracil