Impact of hand-foot skin reaction on treatment outcome in patients receiving capecitabine plus erlotinib for advanced pancreatic cancer: a subgroup analysis from AIO-PK0104.
BACKGROUND
Drug-induced skin toxicity may correlate with treatment efficacy in cancer patients receiving chemotherapy or biological agents. The correlation of the capecitabine-associated hand-foot skin reaction (HFS) on outcome parameters in pancreatic cancer (PC) has not yet been investigated.


METHODS
Within the multicentre phase III AIO-PK0104 trial, patients with confirmed advanced PC were randomly assigned to first-line treatment with either capecitabine plus erlotinib (150 mg/day, arm A) or gemcitabine plus erlotinib (150 mg/day, arm B). A cross-over to either gemcitabine (arm A) or capecitabine (arm B) was performed after failure of the first-line regimen. Data on skin toxicity were correlated with efficacy study endpoints using uni- and multivariate analyses. To control for guarantee-time bias (GTB), we focused on subgroup analyses of patients who had completed two and three or more treatment cycles.


RESULTS
Of 281 randomised patients, skin toxicity data were available for 255 patients. Median time to capecitabine-attributed HFS was two cycles, 36 of 47 (77%) HFS events had been observed by the end of treatment cycle three. Considering HFS during first-line treatment in 101 patients treated with capecitabine for at least two cycles within the capecitabine plus erlotinib arm, time to treatment failure after first- and second-line therapy (TTF2) and overall survival (OS) both were significantly prolonged for the 44 patients (44%) with HFS compared to 57 patients without HFS (56%) (TTF2: 7.8 vs. 3.8 months, HR 0.50, p = 0.001; OS: 10.4 vs. 5.9 months, HR 0.55, p = 0.005). A subgroup analysis of 70 patients on treatment with capecitabine for at least three cycles showed similar results (TTF2: 8.3 vs. 4.4 months, HR 0.53, p = 0.010; OS: 10.4 vs. 6.7 months, HR 0.62, p = 0.056).


CONCLUSIONS
The present subgroup analysis from AIO-PK0104 suggests that HFS may serve as an independent clinical predictor for treatment outcome in capecitabine-treated patients with advanced PC.
Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich , Munich , Germany.
Stephan
S
Kruger
Stefan
S
Boeck
Volker
V
Heinemann
Ruediger P
RP
Laubender
Ursula
U
Vehling-Kaiser
Dirk
D
Waldschmidt
Erika
E
Kettner
Angela
A
Märten
Cornelia
C
Winkelmann
Stefan
S
Klein
Georgi
G
Kojouharoff
Thomas C
TC
Gauler
Ludwig
L
Fischer von Weikersthal
Michael R
MR
Clemens
Michael
M
Geissler
Tim F
TF
Greten
Susanna
S
Hegewisch-Becker
Dominik P
DP
Modest
Sebastian
S
Stintzing
Michael
M
Haas
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D000069287:Capecitabine / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D060831:Hand-Foot Syndrome / Q000453:epidemiology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome; D000093542:Gemcitabine
D003841:Deoxycytidine; D000069287:Capecitabine; D000069347:Erlotinib Hydrochloride; D000093542:Gemcitabine