Phase I evaluation of cediranib, a selective VEGFR signalling inhibitor, in combination with gefitinib in patients with advanced tumours

Cruijsen, Hester van; Voest, Emile E.; Punt, Cornelis J.A.; Hoekman, K.; Witteveen, Petronella O.; Meijerink, Martijn R.; Puchalski, Thomas A.; Robertson, Jane; Saunders, O.; Jürgensmeier, Juliane M.; Herpen, Carla M.L. van; Giaccone, Giuseppe

doi:10.1016/j.ejca.2009.12.023

Cited by 49 publications

(33 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a Phase I study of Japanese patients with advanced solid tumors, cediranib was well tolerated as a monotherapy at doses of ≤30 mg/day [9]. Subsequent Phase I combination studies demonstrated that cediranib was generally well tolerated at doses up to 30 mg/day in combination with various anticancer agents [10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 95%

Phase I results from a two-part Phase I/II study of cediranib in combination with mFOLFOX6 in Japanese patients with metastatic colorectal cancer

et al. 2011

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 95%

Phase I results from a two-part Phase I/II study of cediranib in combination with mFOLFOX6 in Japanese patients with metastatic colorectal cancer

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Combination of cediranib (between 20 and 45 mg once daily) with another TKI, such as gefitinib (250 or 500 mg once daily), led to a 16 % reduction of the cediranib AUC, while the overall pharmacokinetic profile of both drugs in combination did not differ from the data obtained when a monotherapy regimen was introduced [124].…”

Section: Ddismentioning

confidence: 59%

“…Previous pharmacokinetic studies delivered C max values between 52.6 and 93.5 ng/mL 2-3 h post application of a single dose of cediranib 30 mg [116,[123][124][125]. The absolute bioavailability is unknown, as is the effect of food on cediranib pharmacokinetics.…”

Section: Pharmacokineticsmentioning

confidence: 97%

See 1 more Smart Citation

Pharmacokinetic Aspects of Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitors

2015

View full text Add to dashboard Cite

Scientists have identified the impact of angiogenesis on tumor growth and survival. Among other efficient drugs, several small-molecule tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor receptor (VEGFR) have been developed and have already been integrated into the treatment of various advanced malignancies. This review provides a compilation of current knowledge on the pharmacokinetic aspects of all VEGFR-TKIs already approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and of those still under investigation. Additional information on substance metabolism, potential for drug-drug interactions (DDIs), and the need for dose adaptation in patients with predominant renal and/or hepatic impairment has been included. All TKIs introduced in this review were administered orally, allowing for easy drug handling for healthcare professionals and patients. For almost all substances, the maximum plasma concentrations were reached within a short period of time. The majority of the substances showed a high plasma protein binding and their excretion occurred via the feces and, to a lesser extent, via the urine. In most cases, dose adaptation in patients with mild to moderate renal or hepatic impairment is not recommended. Cytochrome P450 (CYP) 3A4 was found to play a crucial role in the drug metabolic processes of many compounds. In order to prevent unwanted DDIs, co-administration of VEGFR TKIs together with CYP3A4 inhibitors or inducers should be avoided. Throughout all TKIs, the data indicate high inter-individual variability. The causes of this are still unclear and require further research to allow for individualization of treatment regimens.

show abstract

“…These findings were translated into a recently published phase 1 evaluation of the safety and tolerability of cediranib in combination with gefitinib, an EGFR tyrosine kinase inhibitor, in patients with advanced tumors. Eight of 90 patients (9%) had a confirmed partial response, including one patient with osteosarcoma, and 38 patients (42%) had stable disease [28]. These results suggest a potential role for dual therapy with cediranib and gefitinib in the targeted treatment of osteosarcoma.…”

Section: Vegfmentioning

confidence: 77%

Stratifying Osteosarcoma: Minimizing and Maximizing Therapy

Niswander

Kim

2010

Curr Oncol Rep

View full text Add to dashboard Cite

Patients who are newly diagnosed with osteosarcoma face a daunting year of medical and surgical therapy, often filled with hospitalizations and changes in lifestyle. Fortunately, the majority of patients endure this struggle to become long-term survivors. However, follow-up studies of cancer survivors are revealing the sequelae of this curative therapy. Just as disturbingly, there remains a large subset of patients for whom conventional therapy is inadequate and who succumb to disease. In this review, we propose that therapeutic strategies for osteosarcoma patients must rely on stratification of patients into risk categories, in order to minimize therapy for some, while expanding treatment for others. We then focus on two molecular targets for the treatment of patients with high-risk osteosarcoma.

show abstract

Phase I evaluation of cediranib, a selective VEGFR signalling inhibitor, in combination with gefitinib in patients with advanced tumours

Cited by 49 publications

References 41 publications

Phase I results from a two-part Phase I/II study of cediranib in combination with mFOLFOX6 in Japanese patients with metastatic colorectal cancer

Phase I results from a two-part Phase I/II study of cediranib in combination with mFOLFOX6 in Japanese patients with metastatic colorectal cancer

Pharmacokinetic Aspects of Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitors

Stratifying Osteosarcoma: Minimizing and Maximizing Therapy

Contact Info

Product

Resources

About