title: Gefitinib in combination with capecitabine as second-line therapy in patients with advanced colorectal cancer (aCRC): a phase I/II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO).
abstract: BACKGROUND
  This phase I/II study was conducted to assess the maximal tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of gefitinib in combination with capecitabine in patients with advanced colorectal cancer (aCRC).
  
  
  METHODS
  After failure of a 1st-line therapy, patients with aCRC received escalating doses of gefitinib once daily in combination with capecitabine twice daily: dose level (DL) 1: gefitinib 250 mg and capecitabine 1,000 mg/m(2), DL 2: gefitinib 250 mg and capecitabine 1,250 mg/m(2), DL 3: gefitinib 500 mg and capecitabine 850 mg/m(2). DLTs were determined after 6 weeks of treatment.
  
  
  RESULTS
  A total of 16 patients were enrolled. On DL1 (n = 6), 1 patient developed a DLT (hand-foot syndrome, HFS n = 1). On DL2 (n = 7), DLTs were observed in 3 patients (exanthema n = 2, HFS n = 1), and on DL3 (n = 3), DLT occurred in 1 patient (HFS n = 1) resulting in recruitment stop at DL3. No patient showed an objective tumor response. Disease stabilization was observed in 6 patients.
  
  
  CONCLUSIONS
  The combination of gefitinib and capecitabine resulted in significant skin toxicities such as exanthema and HFS. As 2nd-line treatment of patients with aCRC, this combination showed no substantial efficacy.
authors.affiliation: Department of Medicine (Cancer Research), West German Cancer Centre, University Hospital, Essen, Germany. tanja.trarbach@uk-essen.de
authors.forename: Tanja
authors.initials: T
authors.lastname: Trarbach
authors.forename: Anke
authors.initials: A
authors.lastname: Reinacher-Schick
authors.forename: Susanne
authors.initials: S
authors.lastname: Hegewisch-Becker
authors.forename: Udo
authors.initials: U
authors.lastname: Vanhoefer
authors.forename: Thomas
authors.initials: T
authors.lastname: Frieling
authors.forename: Lasse
authors.initials: L
authors.lastname: Lehnert
authors.forename: Wolff
authors.initials: W
authors.lastname: Schmiegel
authors.forename: Ullrich
authors.initials: U
authors.lastname: Graeven
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D000069287:Capecitabine; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077156:Gefitinib; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D003841:Deoxycytidine; D000069287:Capecitabine; D000077156:Gefitinib; D005472:Fluorouracil