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A phase I study of volasertib combined with afatinib, in advanced solid tumors

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Machiels, Jean-Pascal [UCL] Peeters, Marc Herremans , Catherine [UCL] Surmont, Veerle Specenier, Pol Rottey, Sylvie

PURPOSE: To determine the maximum tolerated dose (MTD) of volasertib, a Polo-like kinase inhibitor, combined with afatinib, an oral irreversible ErbB family blocker, in patients with advanced solid tumors (NCT01206816; Study 1230.20). METHODS: Patients with advanced non-resectable and/or metastatic disease following failure of conventional treatment received intravenous volasertib 150-300 mg on day 1 every 21 days, combined with oral afatinib 30-40 mg on days 2-21 of a 3-week cycle (Schedule A), or 50-90 mg on days 2-6 of a 3-week cycle (Schedule B). The primary objective was to determine the MTD of volasertib in combination with afatinib. RESULTS: Fifty-seven patients (Schedule A, N = 29; Schedule B, N = 28) were treated. The MTDs were volasertib 300 mg plus afatinib 30 mg days 2-21 and 70 mg days 2-6 of a 3-week cycle for Schedules A and B, respectively. The most common Grade 3/4 adverse events were neutropenia (31.0 %), diarrhea (13.8 %), and thrombocytopenia (10.3 %) in Schedule A; neutropenia (39.3 %), thrombocytopenia (35.7 %), hypokalemia (14.3 %), febrile neutropenia, and nausea (each 10.7 %) in Schedule B. The best overall response was two partial responses (6.9 %; both in Schedule A); eight patients in each schedule achieved stable disease. Volasertib showed multi-exponential pharmacokinetic (PK) behavior; co-administration of volasertib and afatinib had no significant effects on the PK profile of either drug. CONCLUSIONS: Volasertib combined with afatinib had manageable adverse effects and limited antitumor activity in this heavily pretreated population.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2015
Language Anglais
Journal information "Cancer Chemotherapy and Pharmacology" - Vol. 76, no.4, p. 843-851 (2015)
Peer reviewed yes
Publisher Springer ((Germany) Heidelberg)
issn 0344-5704
e-issn 1432-0843
Publication status Publié
Affiliations UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie
UCL - (SLuc) Unité d'oncologie médicale
UCL - (SLuc) Centre du cancer
MESH Subject Administration, Oral ; Humans ; Infusions, Intravenous ; Male ; Neoplasm Metastasis ; Neoplasm Staging ; Neoplasms ; Neutropenia ; Protein Kinase Inhibitors ; Pteridines ; Quinazolines ; Adult ; Severity of Illness Index ; Thrombocytopenia ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; Cohort Studies ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drug Interactions ; Female
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Bibliographic reference Machiels, Jean-Pascal ; Peeters, Marc ; Herremans , Catherine ; Surmont, Veerle ; Specenier, Pol ; et. al. A phase I study of volasertib combined with afatinib, in advanced solid tumors. In: Cancer Chemotherapy and Pharmacology, Vol. 76, no.4, p. 843-851 (2015)
Permanent URL http://hdl.handle.net/2078.1/172043