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Invest New Drugs. 2011 Oct;29(5):978-83. doi: 10.1007/s10637-010-9427-1. Epub 2010 Apr 13.

A phase I evaluation of the combination of vinflunine and erlotinib in patients with refractory solid tumors.

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  • 1Department of Medicine, Division of Hematology-Oncology, School of Medicine, University of North Carolina at Chapel Hill, 170 Manning Drive, 3rd Floor POB, CB 7305, Chapel Hill, NC 27599-7305, USA.

Abstract

PURPOSE:

Epidermal growth factor receptor (EGFR) inhibition may overcome chemotherapy resistance by inhibiting important anti-apoptotic signals that are constitutively activated by an overstimulated EGFR pathway.

METHODS:

This phase I dose escalation trial assessed the safety and efficacy of vinflunine, a novel vinca alkaloid microtubule inhibitor, with erlotinib, an EGFR tyrosine kinase inhibitor, in patients with refractory solid tumors.

RESULTS:

Seventeen patients were treated, 10 with continuous erlotinib, and 7 with intermittent erlotinib. At dose level 1, vinflunine 280 mg/m(2) IV day 1 and erlotinib 75 mg PO days 2-21 ("continuous erlotinib") in 21 day cycles, two of four patients experienced DLTs. At dose level -1 (vinflunine 250 mg/m(2) every 21 days and erlotinib 75 mg/day), two of six patients experienced DLTs. The study was amended to enroll to "intermittent erlotinib" dosing: vinflunine day 1 and erlotinib days 2-15 of a 21 day cycle. Two of seven experienced DLTs and the study was terminated. One patient with breast cancer had a partial response; three had stable disease ≥ 6 cycles. All were treated in the continuous erlotinib group.

CONCLUSIONS:

Given the marked toxicity in our patient population, the combination of vinflunine and erlotinib cannot be recommended for further study with these dosing schemas.

PMID:
20387090
[PubMed - indexed for MEDLINE]
PMCID:
PMC2988886
Free PMC Article
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