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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 6/2015

Open Access 01-06-2015 | Original Article

Phase II study of capecitabine and the oral mTOR inhibitor everolimus in patients with advanced pancreatic cancer

Authors: S. Kordes, H. J. Klümpen, M. J. Weterman, J. H. M. Schellens, D. J. Richel, J. W. Wilmink

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2015

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Abstract

Purpose

The combination of an mTOR inhibitor with 5-fluorouracil-based anticancer therapy is attractive because of preclinical evidence of synergy between these drugs. According to our phase I study, the combination of capecitabine and everolimus is safe and feasible, with potential activity in pancreatic cancer patients.

Methods

Patients with advanced adenocarcinoma of the pancreas were enrolled. Eligible patients had a WHO performance status 0–2 and adequate hepatic and renal functions. The treatment regimen consisted of capecitabine 1000 mg/m2 BID day 1–14 and everolimus 10 mg daily (5 mg BID) in a continuous 21-day schedule. Tumor assessment was performed with CT-scan every three cycles. Primary endpoint was response rate (RR) according to RECIST 1.0. Secondary endpoints were progression-free survival, overall survival and 1-year survival rate.

Results

In total, 31 patients were enrolled. Median (range) treatment duration with everolimus was 76 days (1–431). Principal grade 3/4 toxicities were hyperglycemia (45 %), hand-foot syndrome (16 %), diarrhea (6 %) and mucositis (3 %). Prominent grade 1/2 toxicities were anemia (81 %), rash (65 %), mucositis (58 %) and fatigue (55 %). RR was 6 %. Ten patients (32 %) had stable disease resulting in a disease control rate of 38 %. Median overall survival was 8.9 months (95 % CI 4.6–13.1). Progression-free survival was 3.6 months (95 % CI 1.9–5.3).

Conclusions

The oral regimen with the combination of capecitabine and everolimus is a moderately active treatment for patients with advanced pancreatic cancer, with an acceptable toxicity profile at the applied dose level.
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Metadata
Title
Phase II study of capecitabine and the oral mTOR inhibitor everolimus in patients with advanced pancreatic cancer
Authors
S. Kordes
H. J. Klümpen
M. J. Weterman
J. H. M. Schellens
D. J. Richel
J. W. Wilmink
Publication date
01-06-2015
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 6/2015
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-015-2730-y

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