Erlotinib in combination with pemetrexed for patients with advanced non-small-cell lung cancer (NSCLC): a phase I dose-finding study.

2.50
Hdl Handle:
http://hdl.handle.net/10541/109036
Title:
Erlotinib in combination with pemetrexed for patients with advanced non-small-cell lung cancer (NSCLC): a phase I dose-finding study.
Authors:
Ranson, Malcolm R; Reck, M; Anthoney, A; Hanauske, A-R; Dean, Emma J; Melezinek, I; Klingelschmitt, G; Kletzl, H; Blatter, J; Twelves, C
Abstract:
BACKGROUND: Erlotinib and pemetrexed are approved single agents for second-line treatment of non-small-cell lung cancer (NSCLC) and, in combination, have shown synergistic antitumor activity in NSCLC cell lines. We investigated the safety, pharmacokinetics and preliminary efficacy of combined erlotinib-pemetrexed in patients with refractory advanced NSCLC. PATIENTS AND METHODS: A nonrandomized, open-label, phase IB study was performed in patients with advanced NSCLC whose disease had progressed on or following first-line chemotherapy with a platinum-containing regimen or for whom the erlotinib-pemetrexed combination was considered appropriate. Patients received i.v. pemetrexed 500-700 mg/m(2) every 3 weeks and oral erlotinib 100-150 mg/day. RESULTS: Twenty patients were recruited. The most common adverse events (AEs) were rash, diarrhea and fatigue. Serious AEs occurred in eight patients (three treatment related) and there were eight deaths (none treatment related). Dose-limiting toxic effects were not experienced up to erlotinib 150 mg/day plus pemetrexed 600 mg/m(2). Concurrent administration did not affect pharmacokinetic parameters. Two patients achieved partial responses and nine had stable disease. CONCLUSIONS: Erlotinib-pemetrexed combination is well tolerated at doses equal to the licensed single-agent doses (150 mg/day and 500 mg/m(2), respectively). The good tolerability profile and promising efficacy indicate that this combination warrants further investigation for patients with advanced NSCLC.
Affiliation:
Department of Medical Oncology, University of Manchester, Christie Hospital, Manchester, UK.
Citation:
Erlotinib in combination with pemetrexed for patients with advanced non-small-cell lung cancer (NSCLC): a phase I dose-finding study. 2010: Ann Oncol
Journal:
Annals of Oncology
Issue Date:
5-May-2010
URI:
http://hdl.handle.net/10541/109036
DOI:
10.1093/annonc/mdq246
PubMed ID:
20444843
Type:
Article
Language:
en
ISSN:
1569-8041
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorRanson, Malcolm Ren
dc.contributor.authorReck, Men
dc.contributor.authorAnthoney, Aen
dc.contributor.authorHanauske, A-Ren
dc.contributor.authorDean, Emma Jen
dc.contributor.authorMelezinek, Ien
dc.contributor.authorKlingelschmitt, Gen
dc.contributor.authorKletzl, Hen
dc.contributor.authorBlatter, Jen
dc.contributor.authorTwelves, Cen
dc.date.accessioned2010-08-04T10:43:50Z-
dc.date.available2010-08-04T10:43:50Z-
dc.date.issued2010-05-05-
dc.identifier.citationErlotinib in combination with pemetrexed for patients with advanced non-small-cell lung cancer (NSCLC): a phase I dose-finding study. 2010: Ann Oncolen
dc.identifier.issn1569-8041-
dc.identifier.pmid20444843-
dc.identifier.doi10.1093/annonc/mdq246-
dc.identifier.urihttp://hdl.handle.net/10541/109036-
dc.description.abstractBACKGROUND: Erlotinib and pemetrexed are approved single agents for second-line treatment of non-small-cell lung cancer (NSCLC) and, in combination, have shown synergistic antitumor activity in NSCLC cell lines. We investigated the safety, pharmacokinetics and preliminary efficacy of combined erlotinib-pemetrexed in patients with refractory advanced NSCLC. PATIENTS AND METHODS: A nonrandomized, open-label, phase IB study was performed in patients with advanced NSCLC whose disease had progressed on or following first-line chemotherapy with a platinum-containing regimen or for whom the erlotinib-pemetrexed combination was considered appropriate. Patients received i.v. pemetrexed 500-700 mg/m(2) every 3 weeks and oral erlotinib 100-150 mg/day. RESULTS: Twenty patients were recruited. The most common adverse events (AEs) were rash, diarrhea and fatigue. Serious AEs occurred in eight patients (three treatment related) and there were eight deaths (none treatment related). Dose-limiting toxic effects were not experienced up to erlotinib 150 mg/day plus pemetrexed 600 mg/m(2). Concurrent administration did not affect pharmacokinetic parameters. Two patients achieved partial responses and nine had stable disease. CONCLUSIONS: Erlotinib-pemetrexed combination is well tolerated at doses equal to the licensed single-agent doses (150 mg/day and 500 mg/m(2), respectively). The good tolerability profile and promising efficacy indicate that this combination warrants further investigation for patients with advanced NSCLC.en
dc.languageENG-
dc.language.isoenen
dc.subjectErlotiniben
dc.subjectPharmacokineticsen
dc.subjectLung Canceren
dc.subjectPemetrexeden
dc.subject.meshAdenocarcinoma-
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols-
dc.subject.meshCarcinoma, Large Cell-
dc.subject.meshCarcinoma, Neuroendocrine-
dc.subject.meshCarcinoma, Non-Small-Cell Lung-
dc.subject.meshCarcinoma, Squamous Cell-
dc.subject.meshLung Neoplasms-
dc.titleErlotinib in combination with pemetrexed for patients with advanced non-small-cell lung cancer (NSCLC): a phase I dose-finding study.en
dc.typeArticleen
dc.contributor.departmentDepartment of Medical Oncology, University of Manchester, Christie Hospital, Manchester, UK.en
dc.identifier.journalAnnals of Oncologyen

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