TY - JOUR
TI - Percentage Change in Plasma Cytokeratin 18 Is Associated with Clinical
Outcomes in Patients Receiving Pemetrexed and Carboplatin for the
Adenocarcinoma Subtype of NSCLC
AU - Strimpakos, Alexios S.
AU - Banerji, Udai
AU - Thavasu, Parames and
AU - Tsilimagou, Alexandra
AU - Psyrri, Amanta
AU - Syrigos, Kostas N.
JO - DIAGNOSTIC ONCOLOGY
PY - 2015
VL - 89
TODO - 1
SP - 53-59
PB - Karger
SN - null
TODO - 10.1159/000371711
TODO - Pemetrexed; Adenocarcinoma; Biomarker; Carboplatin; Cytokeratin; Lung
cancer
TODO - Background: The adenocarcinoma subtype of non-small cell lung cancer
(adeno-NSCLC) is routinely treated with chemotherapy if patients do not
have molecular aberrations such as epidermal growth factor receptor
mutations or anaplastic lymphoma kinase rearrangements. There are
currently no validated biomarkers that can predict if patients will gain
clinical benefit from chemotherapy, leading to a majority of patients
receiving many cycles of unnecessary chemotherapy. We hypothesized that
the percentage rise in plasma caspase-cleaved cytokeratin 18 (cCK18) and
total cytokeratin 18 (tCK18) assessed before and after chemotherapy
correlates with the radiological response to chemotherapy. Methods:
Plasma samples from 40 patients with stage IV adeno-NSCLC, treated with
first-line chemotherapy with carboplatin (AUC(5)) plus pemetrexed (500
mg/m(2)), were collected prior to chemotherapy and 48 h after treatment.
ELISA was used to quantify cCK18 and tCK18. Results: The male-to-female
ratio was 3: 1, and the median age of patients was 63 years. Patients
who had a clinical benefit (complete response, partial response or
stable disease) at the first radiological assessment following
chemotherapy had a significantly higher percentage change in plasma
tCK18 levels compared to those who had no clinical benefit, i.e.
progressive disease (69.5 +/- 75.1 vs. 25.3 +/- 30.9%, respectively; p
= 0.042). The receiver operating characteristic area was 0.712 (p =
0.039). There was an increase in the percentage change in cCK18 in
patients with clinical benefit compared to those without clinical
benefit but this was not statistically significant (57.6 +/- 112.8 vs.
24.38 +/- 45.1%, respectively; p = 0.85). Conclusions: The percentage
change in plasma tCK18 levels before and after the first cycle of
pemetrexed and carboplatin chemotherapy is associated with clinical
benefit. If validated in larger cohorts, this test can be used to
identify patients unlikely to respond to treatment who can thus be
offered alternative treatments or entry into clinical trials. (C) 2015
S. Karger AG, Basel
ER -