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2014 ; 120
(19
): 2980-5
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Dual blockade of epidermal growth factor receptor and insulin-like growth factor
receptor-1 signaling in metastatic pancreatic cancer: phase Ib and randomized
phase II trial of gemcitabine, erlotinib, and cixutumumab versus gemcitabine plus
erlotinib (SWOG S0727)
#MMPMID25041791
Philip PA
; Goldman B
; Ramanathan RK
; Lenz HJ
; Lowy AM
; Whitehead RP
; Wakatsuki T
; Iqbal S
; Gaur R
; Benedetti JK
; Blanke CD
Cancer
2014[Oct]; 120
(19
): 2980-5
PMID25041791
show ga
BACKGROUND: Targeting a single pathway in pancreatic adenocarcinoma (PC) is
unlikely to affect its natural history. We tested the hypothesis that
simulataneous targeting of the epidermal growth factor receptor (EGFR) and
insulin-like growth factor receptor-1 (IGF-1R) pathways would significantly
improve progression-free survival (PFS) by abrogating reciprocal signaling that
promote drug resistance METHODS: This was a phase Ib/II study testing
cixutumumab, combined with erlotinib and gemcitabine (G) in patients with
untreated metastatic PC. The control arm was erlotinib plus G. The primary end
point was PFS. Eligibility included performance status 0/1 and normal fasting
blood glucose. Polymorphisms in genes involved in G metabolism and in the EGFR
pathway were also studied RESULTS: The phase I results (n?=?10) established the
safety of cixutumumab 6 mg/kg/week intravenously, erlotinib 100 mg/day orally,
and G 1000 mg/m(2) intravenously on days 1, 8, and 15 of a 28-day cycle. In the
RP2 portion (116 eligible patients; median age, 63), the median PFS and overall
survival (OS) were 3.6 and 7.0 months, respectively, on the cixutumumab arm, and
3.6 and 6.7 months, respecively, on the control arm. Major grades 3 and 4
toxicities with cixutumumab and control were elevation of transaminases, 12% and
6%, respectively; fatigue, 16% and 12%, respectively; gastrointestinal, 35% and
28%, respectively; neutropenia, 21% and 10%, respectively; and thrombocytopenia,
16% and 7%, respecively. Grade 3/4 hyperglycemia was seen in 16% of patients on
cixutumumab. Grade 3 or 4 skin toxicity was similar in both arms of the study (<
5%). No significant differences in PFS by genotype were seen for any of the
polymorphisms. CONCLUSIONS: Adding the IGF-1R inhibitor cixutumumab to erlotinib
and G did not lead to longer PFS or OS in metastatic PC.