Universität zu Köln

Vansteenkiste, Johan, Solomon, Benjamin, Boyer, Michael ORCID: 0000-0002-0452-2987, Wolf, Juergen, Miller, Neil, Di Scala, Lilla, Pylvaenaeinen, Ilona, Petrovic, Katarina, Dimitrijevic, Sasa, Anrys, Beatrijs and Laack, Eckart (2011). Everolimus in Combination with Pemetrexed in Patients with Advanced Non-small Cell Lung Cancer Previously Treated with Chemotherapy A Phase I Study Using a Novel, Adaptive Bayesian Dose-Escalation Model. J. Thorac. Oncol., 6 (12). S. 2120 - 2130. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1556-1380

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Abstract

Introduction: Pemetrexed is an established second-line therapy for non-small cell lung cancer (NSCLC). Everolimus has previously been shown to have some clinical activity when used as a single agent in NSCLC. The aim of this phase I study was to evaluate the safety and feasibility of combining pemetrexed with everolimus in patients with NSCLC who had disease progression after one previous treatment. Methods: Patients with stage IIIb/IV NSCLC and one previous chemotherapy regimen were enrolled. A Bayesian dose-escalation model was used to determine the feasible doses of daily or weekly everolimus combined with pemetrexed (500 mg/m(2) q3w). The primary end point was rate of cycle 1 dose-limiting toxicities (DLTs). Secondary end points included safety, relative dose intensity of pemetrexed, pharmacokinetics, and tumor response. Results: Twenty-four patients received daily everolimus (2.5, 5, 7.5, or 10 mg) and 19 received weekly everolimus (30 or 50 mg) with pemetrexed. Cycle 1 DLTs in the daily regimen included febrile neutropenia, neutropenia, rash/pruritus, and thrombocytopenia; in the weekly regimen, DLTs included neutropenia and stomatitis. The most frequent grade 3/4 adverse events were neutropenia, dyspnea, and thrombocytopenia. Three partial responses were observed with everolimus 5 mg/d and two with 50 mg/wk. Pharmacokinetics did not suggest an influence of everolimus on pemetrexed parameters; pemetrexed resulted in a minor decrease in everolimus exposure with both daily and weekly regimens. Conclusions: Everolimus 5 mg/d or 50 mg/wk with the standard regimen of pemetrexed are feasible dosages in patients with stage IIIb/IV NSCLC.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Vansteenkiste, Johan UNSPECIFIED UNSPECIFIED UNSPECIFIED Solomon, Benjamin UNSPECIFIED UNSPECIFIED UNSPECIFIED Boyer, Michael UNSPECIFIED orcid.org/0000-0002-0452-2987 UNSPECIFIED Wolf, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Miller, Neil UNSPECIFIED UNSPECIFIED UNSPECIFIED Di Scala, Lilla UNSPECIFIED UNSPECIFIED UNSPECIFIED Pylvaenaeinen, Ilona UNSPECIFIED UNSPECIFIED UNSPECIFIED Petrovic, Katarina UNSPECIFIED UNSPECIFIED UNSPECIFIED Dimitrijevic, Sasa UNSPECIFIED UNSPECIFIED UNSPECIFIED Anrys, Beatrijs UNSPECIFIED UNSPECIFIED UNSPECIFIED Laack, Eckart UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-484293
DOI:	10.1097/JTO.0b013e3182307ede
Journal or Publication Title:	J. Thorac. Oncol.
Volume:	6
Number:	12
Page Range:	S. 2120 - 2130
Date:	2011
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1556-1380
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CISPLATIN PLUS GEMCITABINE; III TRIAL; CLINICAL-TRIALS; EFFICACY; RESISTANCE; CETUXIMAB; PLACEBO Multiple languages Oncology; Respiratory System Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48429