BACKGROUND: Vandetanib is a tyrosine kinase inhibitor of both the vascular endothelial growth factor (VEGFR) and epidermal growth factor (EGFR) receptors. The primary objectives of this study were to determine the maximum tolerated dose of vandetanib with capecitabine and oxaliplatin, without and with bevacizumab, for the first line treatment of metastatic colorectal cancer (mCRC), and to define the dose limiting toxicities. MATERIALS AND METHODS: Three cohorts of patients were studied, with capecitabine at 1,000 mg/m(2) twice daily p.o. on days 1-14 of a 3 week cycle, with oxaliplatin i.v. at 130 mg/m(2) on day 1. Vandetanib dosing was 100 mg/day in cohort 1 and 300 mg/day in cohorts 2 and 3. Bevacizumab was added in cohort 3 at 7.5 mg/kg i.v. on day 1 every 3 weeks. RESULTS: Thirteen patients were enrolled and received from one to eight cycles per patient. Grade 4 dermatitis developed in one patient in the first cohort, and the cohort was expanded to six patients with no further dose limiting toxicities (DLT). The second cohort of 3 patients was well tolerated. The third cohort resulted in grade 3 diarrhea, requiring several days of hospitalization and i.v. hydration, in 3 of the 4 patients. Given the severity and duration of diarrhea, each of these was considered a DLT, and therefore cohort 3 was considered to be above the maximum tolerated dose. Six of the 13 patients achieved a partial or complete remission (46%). The time to progression ranged from 2 to 14 months. CONCLUSIONS: Vandetanib at doses of 100 mg and 300 mg daily in combination with capecitabine and oxaliplatin was well tolerated. However, the addition of bevacizumab resulted in severe diarrhea in three out of four patients. Bevacizumab was not well tolerated with vandetanib and XELOX in combination.
BACKGROUND: Vandetanib is a tyrosine kinase inhibitor of both the vascular endothelial growth factor (VEGFR) and epidermal growth factor (EGFR) receptors. The primary objectives of this study were to determine the maximum tolerated dose of vandetanib with capecitabine and oxaliplatin, without and with bevacizumab, for the first line treatment of metastatic colorectal cancer (mCRC), and to define the dose limiting toxicities. MATERIALS AND METHODS: Three cohorts of patients were studied, with capecitabine at 1,000 mg/m(2) twice daily p.o. on days 1-14 of a 3 week cycle, with oxaliplatin i.v. at 130 mg/m(2) on day 1. Vandetanib dosing was 100 mg/day in cohort 1 and 300 mg/day in cohorts 2 and 3. Bevacizumab was added in cohort 3 at 7.5 mg/kg i.v. on day 1 every 3 weeks. RESULTS: Thirteen patients were enrolled and received from one to eight cycles per patient. Grade 4 dermatitis developed in one patient in the first cohort, and the cohort was expanded to six patients with no further dose limiting toxicities (DLT). The second cohort of 3 patients was well tolerated. The third cohort resulted in grade 3 diarrhea, requiring several days of hospitalization and i.v. hydration, in 3 of the 4 patients. Given the severity and duration of diarrhea, each of these was considered a DLT, and therefore cohort 3 was considered to be above the maximum tolerated dose. Six of the 13 patients achieved a partial or complete remission (46%). The time to progression ranged from 2 to 14 months. CONCLUSIONS: Vandetanib at doses of 100 mg and 300 mg daily in combination with capecitabine and oxaliplatin was well tolerated. However, the addition of bevacizumab resulted in severe diarrhea in three out of four patients. Bevacizumab was not well tolerated with vandetanib and XELOX in combination.
Authors: Timothy Kuo; Cheryl D Cho; Joanne Halsey; Heather A Wakelee; Ranjana H Advani; James M Ford; George A Fisher; Branimir I Sikic Journal: J Clin Oncol Date: 2005-08-20 Impact factor: 44.544
Authors: Jeffrey L Evelhoch; Patricia M LoRusso; Zhanquan He; Zachary DelProposto; Lisa Polin; Thomas H Corbett; Peter Langmuir; Catherine Wheeler; Andrew Stone; Joanna Leadbetter; Anderson J Ryan; David C Blakey; John C Waterton Journal: Clin Cancer Res Date: 2004-06-01 Impact factor: 12.531
Authors: Elizabeth R Kessler; S Gail Eckhardt; Todd M Pitts; Erica L Bradshaw-Pierce; Cindy L O'byrant; Wells A Messersmith; Sujatha Nallapreddy; Colin Weekes; Jennifer Spratlin; Christopher H Lieu; Madeleine A Kane; Sarah Eppers; Elizabeth Freas; Stephen Leong Journal: Invest New Drugs Date: 2015-12-30 Impact factor: 3.850
Authors: Philipp Harter; Jalid Sehouli; Rainer Kimmig; Jörn Rau; Felix Hilpert; Christian Kurzeder; Gabriele Elser; Andreas du Bois Journal: Invest New Drugs Date: 2013-09-05 Impact factor: 3.850
Authors: Laura Beaton; Henry F J Tregidgo; Sami A Znati; Sharon Forsyth; Matthew J Clarkson; Steven Bandula; Manil Chouhan; Helen L Lowe; May Zaw Thin; Julian Hague; Dinesh Sharma; Joerg-Matthias Pollok; Brian R Davidson; Jowad Raja; Graham Munneke; Daniel J Stuckey; Zainab A Bascal; Paul E Wilde; Sarah Cooper; Samantha Ryan; Peter Czuczman; Eveline Boucher; John A Hartley; Andrew L Lewis; Marnix Jansen; Tim Meyer; Ricky A Sharma Journal: JMIR Res Protoc Date: 2019-10-02