Literature DB >> 20530436

A phase I dose-escalation study of imatinib mesylate (Gleevec/STI571) plus capecitabine (Xeloda) in advanced solid tumors.

Elizabeth Dugan1, Roxanne Truax, Kellen L Meadows, Andrew B Nixon, William P Petros, Justin Favaro, Nishan H Fernando, Michael A Morse, Gerard C Blobe, Herbert I Hurwitz.   

Abstract

UNLABELLED: The aim of this study was to determine the maximally tolerated dose, recommended phase II dose and toxicity profile of capecitabine plus imatinib mesylate combination. PATIENTS AND METHODS: Twenty-four patients with advanced solid tumors were treated with capecitabine twice daily on days 1-14 and imatinib mesylate once daily on a 21-day cycle. Dose-limiting toxicity was assessed during the first cycle. Treatment continued until disease progression or undesirable toxicity.
RESULTS: Six patients were treated with capecitabine at 1000 mg/m(2) and imatinib mesylate 300 mg; unacceptable toxicity due to grade 2 intolerable hand-foot syndrome and/or grade > or = 2 diarrhea was observed. Doses were subsequently reduced to capecitabine at 750 mg/m(2) and imatinib mesylate at 300 mg; toxicities were better tolerated at the lower dose. Dose-limiting toxicities consisted of grade 3 diarrhea, anorexia and fatigue lasting > or = 4 days. Treatment-related adverse events greater than or equal to grade 3 included anemia, diarrhea, dysuria, hypophosphatemia and vertigo. Minor responses were observed in two patients: stable disease > or = 6 months was observed in two out of twenty-one evaluable patients.
CONCLUSION: Full doses of capecitabine and imatinib mesylate were not tolerable. The maximum tolerated dose and the recommended phase II dose for this drug combination is capecitabine at 750 mg/m(2) twice daily for 1-14 days and imatinib at 300 mg once daily on a 21-day cycle.

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Year:  2010        PMID: 20530436      PMCID: PMC4103189     

Source DB:  PubMed          Journal:  Anticancer Res        ISSN: 0250-7005            Impact factor:   2.480


  15 in total

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Journal:  J Clin Oncol       Date:  2001-11-01       Impact factor: 44.544

4.  The activity and expression of thymidine phosphorylase in human solid tumours.

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Journal:  Eur J Cancer       Date:  1996-06       Impact factor: 9.162

5.  Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients.

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6.  Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia.

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Journal:  N Engl J Med       Date:  2002-08-15       Impact factor: 91.245

8.  Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia.

Authors:  Stephen G O'Brien; François Guilhot; Richard A Larson; Insa Gathmann; Michele Baccarani; Francisco Cervantes; Jan J Cornelissen; Thomas Fischer; Andreas Hochhaus; Timothy Hughes; Klaus Lechner; Johan L Nielsen; Philippe Rousselot; Josy Reiffers; Giuseppe Saglio; John Shepherd; Bengt Simonsson; Alois Gratwohl; John M Goldman; Hagop Kantarjian; Kerry Taylor; Gregor Verhoef; Ann E Bolton; Renaud Capdeville; Brian J Druker
Journal:  N Engl J Med       Date:  2003-03-13       Impact factor: 91.245

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10.  Inhibition of collagen-induced discoidin domain receptor 1 and 2 activation by imatinib, nilotinib and dasatinib.

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Journal:  Eur J Pharmacol       Date:  2008-10-11       Impact factor: 4.432

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Journal:  Oncoimmunology       Date:  2013-02-01       Impact factor: 8.110

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