title: Erlotinib 150 mg daily plus chemotherapy in advanced pancreatic cancer: an interim safety analysis of a multicenter, randomized, cross-over phase III trial of the 'Arbeitsgemeinschaft Internistische Onkologie'.
abstract: To date, only limited toxicity data are available for the combination of erlotinib with either capecitabine or gemcitabine as front-line therapy for advanced pancreatic cancer. Within a randomized phase III trial, 281 treatment-naive patients were randomly assigned between capecitabine (2000 mg/m/day, for 14 days, once every 3 weeks) plus erlotinib (150 mg/day, arm A) and gemcitabine (1000 mg/m as a 30-min infusion) plus erlotinib (150 mg/day, arm B). In case of treatment failure, patients were crossed over to a second-line treatment with the comparator cytostatic drug without erlotinib. The primary study endpoint was the time to treatment failure of second-line therapy (TTF2). This interim analysis of toxicity contains safety data from the first 127 randomized patients. During first-line therapy, patients received a median number of three treatment cycles (range 0-13) in both the arms. Regarding chemotherapy, a treatment delay was observed in 12% of the cycles in arm A and in 22% of the cycles in arm B. Dose reductions of the cytostatic drug were performed in 18 and 27% of treatment cycles, respectively. Erlotinib dose reductions were performed in 6 and 11% of all cycles. Grade 3/4 hematological toxicity was <10% in both the arms; major grade 3/4 toxicities in arms A and B were diarrhea (9 vs. 7%), skin rash (4 vs. 12%), and hand-foot syndrome (7 vs. 0%). No treatment-related death was observed. In conclusion, this interim safety analysis suggests that treatment with erlotinib 150 mg/day is feasible in combination with capecitabine or gemcitabine.
authors.affiliation: Department of Internal Medicine III, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Boeck
authors.forename: Ursula
authors.initials: U
authors.lastname: Vehling-Kaiser
authors.forename: Dirk
authors.initials: D
authors.lastname: Waldschmidt
authors.forename: Erika
authors.initials: E
authors.lastname: Kettner
authors.forename: Angela
authors.initials: A
authors.lastname: Märten
authors.forename: Cornelia
authors.initials: C
authors.lastname: Winkelmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Klein
authors.forename: Georgi
authors.initials: G
authors.lastname: Kojouharoff
authors.forename: Thomas
authors.initials: T
authors.lastname: Gauler
authors.forename: Ludwig
authors.initials: L
authors.lastname: Fischer von Weikersthal
authors.forename: Michael R
authors.initials: MR
authors.lastname: Clemens
authors.forename: Michael
authors.initials: M
authors.lastname: Geissler
authors.forename: Tim F
authors.initials: TF
authors.lastname: Greten
authors.forename: Susanna
authors.initials: S
authors.lastname: Hegewisch-Becker
authors.forename: Sascha
authors.initials: S
authors.lastname: Neugebauer
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use*; D000069287:Capecitabine; D018592:Cross-Over Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D004334:Drug Administration Schedule; D000069347:Erlotinib Hydrochloride; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D046790:Pancreas, Exocrine / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011446:Prospective Studies; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000093542:Gemcitabine
chemical_list: D011799:Quinazolines; D003841:Deoxycytidine; D000069287:Capecitabine; D000069347:Erlotinib Hydrochloride; D005472:Fluorouracil; D000093542:Gemcitabine