Phase I trial of volasertib, a Polo-like kinase inhibitor, plus platinum agents in solid tumors: safety, pharmacokinetics and activity

Investigational New Drugs
Ahmad AwadaPatrick Schöffski

Abstract

This trial evaluated the maximum tolerated dose (MTD), safety, pharmacokinetics, and activity of volasertib, a selective Polo-like kinase 1 inhibitor that induces mitotic arrest and apoptosis, combined with cisplatin or carboplatin in patients with advanced/metastatic solid tumors (NCT00969761; 1230.6). Sequential patient cohorts (3 + 3 dose-escalation design) received a single infusion of volasertib (100-350 mg) with cisplatin (60-100 mg/m(2)) or carboplatin (area under the concentration versus time curve [AUC]4-AUC6) on day 1 every 3 weeks for up to six cycles. Sixty-one patients received volasertib/cisplatin (n = 30) or volasertib/carboplatin (n = 31) for a median of 3.5 (range, 1-6) and 2.0 (range, 1-6) treatment cycles, respectively. The most common cycle 1 dose-limiting toxicities (DLTs) were thrombocytopenia, neutropenia and fatigue. MTDs (based on cycle 1 DLTs) were determined to be volasertib 300 mg plus cisplatin 100 mg/m(2) and volasertib 300 mg plus carboplatin AUC6. Co-administration did not affect the pharmacokinetics of each drug. Partial responses were observed in two patients in each arm. Stable disease was achieved in 11 and six patients treated with volasertib/cisplatin and volasertib/carboplatin, respectivel...Continue Reading

References

Oct 1, 1991·Clinical Pharmacokinetics·W J van der Vijgh
Nov 1, 1989·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·A H CalvertE Wiltshaw
Oct 7, 1997·Clinical Pharmacokinetics·S B Duffull, B A Robinson
Dec 19, 2002·Journal of the National Cancer Institute·Birgit Spänkuch-SchmittKlaus Strebhardt
Apr 24, 2003·Cancer Science·Takao TakahashiShigetoyo Saji
May 7, 2003·Proceedings of the National Academy of Sciences of the United States of America·Xiaoqi Liu, Raymond L Erikson
Mar 25, 2006·Nature Reviews. Cancer·Klaus Strebhardt, Axel Ullrich
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
Jul 31, 2010·Nature Reviews. Drug Discovery·Klaus Strebhardt
Nov 9, 2011·The International Journal of Biochemistry & Cell Biology·Zhao-Xia WangYong-Mei Yin
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
Jun 1, 2012·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Ding-pei HanAi-guo Lu

❮ Previous
Next ❯

Citations

May 4, 2016·Medicinal Research Reviews·J Van den BosscheA Wouters
Nov 20, 2019·Oncotarget·Dina KatsCharles Keller
Nov 15, 2016·International Journal of Oncology·Tatsuya KatoKazuhiro Yasufuku
May 1, 2021·International Journal of Molecular Sciences·Youri OhJung-Mi Hah
Nov 12, 2020·Journal of Medicinal Chemistry·Celeste N AlverezKyung S Lee

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft

Clinical Trials Mentioned

NCT00969761

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis