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

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/m(2) 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.

authors

Kordes S,Klümpen HJ,Weterman MJ,Schellens JH,Richel DJ,Wilmink JW

doi

10.1007/s00280-015-2730-y

subject

Has Abstract

pub_date

2015-06-01 00:00:00

pages

1135-41

issue

6

eissn

0344-5704

issn

1432-0843

journal_volume

75

pub_type

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