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'

Anticancer Drugs. 2010 Jan;21(1):94-100. doi: 10.1097/CAD.0b013e32833123ed.

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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Capecitabine
  • Cross-Over Studies
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Drug Administration Schedule
  • Erlotinib Hydrochloride
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Fluorouracil / analogs & derivatives
  • Fluorouracil / therapeutic use
  • Gemcitabine
  • Germany
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Pancreas, Exocrine / pathology
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Prospective Studies
  • Quinazolines / administration & dosage
  • Quinazolines / adverse effects
  • Quinazolines / therapeutic use

Substances

  • Quinazolines
  • Deoxycytidine
  • Capecitabine
  • Erlotinib Hydrochloride
  • Fluorouracil
  • Gemcitabine