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

Cancer Chemotherapy and Pharmacology
Jean-Pascal MachielsSylvie Rottey

Abstract

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). 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. 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. Vol...Continue Reading

References

Jul 1, 1995·Critical Reviews in Oncology/hematology·D S SalomonN Normanno
Aug 24, 1999·Pharmacology & Therapeutics·J R Woodburn
Apr 24, 2003·Cancer Science·Takao TakahashiShigetoyo Saji
May 3, 2005·Nature Reviews. Cancer·Nancy E Hynes, Heidi A Lane
Jul 11, 2006·Nature Reviews. Molecular Cell Biology·Ami Citri, Yosef Yarden
Mar 14, 2008·The New England Journal of Medicine·Fortunato Ciardiello, Giampaolo Tortora
Dec 23, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·E A EisenhauerJ Verweij
Apr 23, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Dorothea RudolphGünther R Adolf
Jun 19, 2009·Nature Reviews. Cancer·José Baselga, Sandra M Swain
Jul 31, 2010·Nature Reviews. Drug Discovery·Klaus Strebhardt
Aug 4, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Timothy A YapRuth Plummer
Oct 18, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·René H MedemaJames Chih-Hsin Yang
Nov 29, 2011·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Patrick SchöffskiGerd Munzert
Dec 28, 2011·Cancer Chemotherapy and Pharmacology·Peter StopferThomas Ebner
Aug 14, 2012·The Journal of Pharmacology and Experimental Therapeutics·Flavio SolcaGuenther R Adolf

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Citations

Mar 5, 2016·European Journal of Pharmacology·George LiamisMoses S Elisaf
May 4, 2016·Medicinal Research Reviews·J Van den BosscheA Wouters
Nov 15, 2016·International Journal of Oncology·Tatsuya KatoKazuhiro Yasufuku
Nov 12, 2020·Journal of Medicinal Chemistry·Celeste N AlverezKyung S Lee

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