BACKGROUND: Cediranib is a highly potent vascular endothelial growth factor (VEGF) signaling inhibitor of all three VEGF receptors. This phase I, single-center, dose-finding study was designed primarily to investigate the safety and pharmacokinetics (PK) of cediranib with various anticancer regimens in patients with advanced solid tumors. EXPERIMENTAL DESIGN: Oral cediranib 20, 30, and/or 45 mg/day was given in combination with standard mFOLFOX6; docetaxel; irinotecan; irinotecan and cetuximab; or pemetrexed. The novel study design allowed simultaneous evaluation of the safety and PK of these regimens with cediranib in one study. Secondary assessments included a preliminary evaluation of efficacy. RESULTS: Fifty-nine patients received cediranib and were evaluable for safety. The most common adverse events across the study were fatigue and diarrhea (both n = 52). The most common CTC grade ≥ 3 adverse events were neutropenia (n = 19) and fatigue (n = 16). Cediranib did not appear to have a major effect on the PK profile of any chemotherapy agent tested. A preliminary assessment of efficacy showed that objective responses were achieved in some patients (n = 6) who had previously progressed on similar regimens without cediranib. CONCLUSION: In this group of heavily pretreated patients, the study design permitted simultaneous assessment of multiple treatment arms. Treatment with cediranib and the various anticancer regimens was generally well tolerated, with no apparent PK interaction and preliminary evidence of antitumor activity.
BACKGROUND:Cediranib is a highly potent vascular endothelial growth factor (VEGF) signaling inhibitor of all three VEGF receptors. This phase I, single-center, dose-finding study was designed primarily to investigate the safety and pharmacokinetics (PK) of cediranib with various anticancer regimens in patients with advanced solid tumors. EXPERIMENTAL DESIGN: Oral cediranib 20, 30, and/or 45 mg/day was given in combination with standard mFOLFOX6; docetaxel; irinotecan; irinotecan and cetuximab; or pemetrexed. The novel study design allowed simultaneous evaluation of the safety and PK of these regimens with cediranib in one study. Secondary assessments included a preliminary evaluation of efficacy. RESULTS: Fifty-nine patients received cediranib and were evaluable for safety. The most common adverse events across the study were fatigue and diarrhea (both n = 52). The most common CTC grade ≥ 3 adverse events were neutropenia (n = 19) and fatigue (n = 16). Cediranib did not appear to have a major effect on the PK profile of any chemotherapy agent tested. A preliminary assessment of efficacy showed that objective responses were achieved in some patients (n = 6) who had previously progressed on similar regimens without cediranib. CONCLUSION: In this group of heavily pretreated patients, the study design permitted simultaneous assessment of multiple treatment arms. Treatment with cediranib and the various anticancer regimens was generally well tolerated, with no apparent PK interaction and preliminary evidence of antitumor activity.
Authors: P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther Journal: J Natl Cancer Inst Date: 2000-02-02 Impact factor: 13.506
Authors: John M Maris; Joshua Courtright; Peter J Houghton; Christopher L Morton; Richard Gorlick; E Anders Kolb; Richard Lock; Mayamin Tajbakhsh; C Patrick Reynolds; Stephen T Keir; Jianrong Wu; Malcolm A Smith Journal: Pediatr Blood Cancer Date: 2008-03 Impact factor: 3.167
Authors: Herbert Hurwitz; Louis Fehrenbacher; William Novotny; Thomas Cartwright; John Hainsworth; William Heim; Jordan Berlin; Ari Baron; Susan Griffing; Eric Holmgren; Napoleone Ferrara; Gwen Fyfe; Beth Rogers; Robert Ross; Fairooz Kabbinavar Journal: N Engl J Med Date: 2004-06-03 Impact factor: 91.245
Authors: Jon O Curwen; Helen L Musgrove; Jane Kendrew; Graham H P Richmond; Donald J Ogilvie; Stephen R Wedge Journal: Clin Cancer Res Date: 2008-05-15 Impact factor: 12.531
Authors: Joachim Drevs; Patrizia Siegert; Michael Medinger; Klaus Mross; Ralph Strecker; Ute Zirrgiebel; Jan Harder; Hubert Blum; Jane Robertson; Juliane M Jürgensmeier; Thomas A Puchalski; Helen Young; Owain Saunders; Clemens Unger Journal: J Clin Oncol Date: 2007-07-20 Impact factor: 44.544
Authors: Robert M Jotte; Daniel D Von Hoff; Fadi Braiteh; Carlos R Becerra; Donald A Richards; David A Smith; Lawrence Garbo; Joe Stephenson; Paul R Conkling; Francisco Robert-Vizcarrondo; Jian Chen; P Kellie Turner; Kay Hoong Chow; D Fritz Tai; Robert Ilaria Journal: Invest New Drugs Date: 2014-09-28 Impact factor: 3.850
Authors: Christopher L Morton; John M Maris; Stephen T Keir; Richard Gorlick; E Anders Kolb; Catherine A Billups; Jianrong Wu; Malcolm A Smith; Peter J Houghton Journal: Pediatr Blood Cancer Date: 2011-04-29 Impact factor: 3.167
Authors: D Cunningham; R P W Wong; G D'Haens; J-Y Douillard; J Robertson; A M Stone; E Van Cutsem Journal: Br J Cancer Date: 2013-01-08 Impact factor: 7.640