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'.
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.
Boeck
Stefan
S
Department of Internal Medicine III, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany.
Vehling-Kaiser
Ursula
U
Waldschmidt
Dirk
D
Kettner
Erika
E
Märten
Angela
A
Winkelmann
Cornelia
C
Klein
Stefan
S
Kojouharoff
Georgi
G
Gauler
Thomas
T
Fischer von Weikersthal
Ludwig
L
Clemens
Michael R
MR
Geissler
Michael
M
Greten
Tim F
TF
Hegewisch-Becker
Susanna
S
Neugebauer
Sascha
S
Heinemann
Volker
V
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
D011799:Quinazolines; D003841:Deoxycytidine; D000069287:Capecitabine; D000069347:Erlotinib Hydrochloride; D005472:Fluorouracil; D000093542:Gemcitabine