Selective kinase inhibition with daily imatinib intensifies toxicity of chemotherapy in patients with solid tumours

European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
Suzanne GeorgeGeorge D Demetri

Abstract

The aim of this study was to determine the safety and maximum-tolerated doses of imatinib combined with cytotoxic chemotherapy (either gemcitabine or doxorubicin). Patients with advanced solid tumours were enrolled separately in two different combinations of imatinib with chemotherapy (imatinib + gemcitabine or imatinib + doxorubicin). A standard modified Fibonacci inter-cohort dose escalation was planned for each combination. Sixteen patients were accrued. Seven patients received gemcitabine and imatinib. A separate cohort of nine patients received imatinib and doxorubicin. In both groups, dose-limiting toxicity (DLT) was observed at the initial dose level requiring dose reductions for subsequent cohorts. Further DLTs were observed necessitating closure of the protocol. Daily dosing of imatinib with concurrent administration of cytotoxic chemotherapy (either gemcitabine or doxorubicin) at standard doses was associated with toxicity that was clinically unacceptable. It remains unclear whether addition of growth factors might improve tolerability for imatininb in combination with cytotoxic chemotherapy.

References

May 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·H N AntoniadesC J O'Hara
Apr 5, 2001·The New England Journal of Medicine·B J DrukerC L Sawyers
Apr 6, 2001·Blood·K OkudaJ D Griffin
Mar 1, 2002·The New England Journal of Medicine·Hagop KantarjianUNKNOWN International STI571 CML Study Group
Aug 1, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jordan D BerlinAl Bowen Benson
Aug 16, 2002·The New England Journal of Medicine·George D DemetriHeikki Joensuu
Aug 31, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Brian P RubinJames D Bruckner
Sep 5, 2002·International Journal of Cancer. Journal International Du Cancer·Robert G MakiCristina R Antonescu
Mar 15, 2003·The New England Journal of Medicine·Stephen G O'BrienUNKNOWN IRIS Investigators
Sep 6, 2003·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·J VerweijO S Nielsen
Oct 8, 2003·The Oncologist·Gregory D LeonardSusan E Bates
Mar 12, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hans MindermanMaria R Baer

❮ Previous
Next ❯

Citations

Aug 11, 2010·Investigational New Drugs·Biren SaraiyaElizabeth A Poplin
Jul 14, 2011·Annals of Oncology : Official Journal of the European Society for Medical Oncology·N StarlingD Cunningham
Mar 10, 2016·Archivum Immunologiae Et Therapiae Experimentalis·Małgorzata PrzybyszewskaSergiusz Markowicz
Mar 15, 2006·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Stefan Sleijfer
Nov 16, 2011·Clinical Medicine Insights. Oncology·Rhonda L BittingDaniel J George
Jun 6, 2019·Frontiers in Oncology·Milea J M TimbergenErik A C Wiemer
Oct 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yaqoob AliElizabeth A Poplin
Jan 21, 2020·Bulletin du cancer·Sébastien Salas, Frédéric Chibon

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Incidence & Mortality

Cancer has emerged as a global concern due to its increase in incidence and mortality. Efforts are underway to evaluate and develop action plans to reduce the global burden of cancer. Currently, lung cancer, breast cancer and prostate cancer are the leading causes of cancer mortality. Here is the latest research on cancer incidence and mortality.