Sunitinib malate for the treatment of solid tumours: a review of current clinical data

Motzer, Robert J.; Hoosen, Sakina; Bello, Carlo L.; Christensen, James G.

doi:10.1517/13543784.15.5.553

Cited by 112 publications

(54 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, many efforts are now focussed on the search of compounds interfering with the cancer cell invasion process and expressing antiangiogenic properties [1]. Examples of drugs, among which monoclonal antibodies and small molecules, are currently under clinical investigation and some of them have recently been approved for use in man in the treatment of several cancers associated or not with conventional chemotherapies or radiation therapies [2][3][4][5][6][7][8][9]. These drugs comprise vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) inhibitors (monoclonal antibodies) as well as VEGF and EGF receptor tyrosine kinase inhibitors (small-molecule inhibitors), but also matrix metalloproteinase (MMP), urokinase (uPA), cycloogygenase-2 (COX-2) or methionine aminopeptidase inhibitors [1].…”

Section: Introductionmentioning

confidence: 99%

6-Substituted 2-oxo-2H-1-benzopyran-3-carboxylic acid derivatives in a new approach of the treatment of cancer cell invasion and metastasis

Kempen

Hemmer

Counerotte

et al. 2008

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

Novel 6-substituted 2-oxo-2H-1-benzopyran-3-carboxylic acid derivatives were synthesized and their potency in reducing the invasive behaviour of HT 1080 fibrosarcoma cells was evaluated. Structure-activity relationships were deduced from biological results and will be used in further design of new active compounds. In particular, the acetoxymethyl substituent found at the 6-position of previously described active compounds can be replaced by an acetamidomethyl substituent without loss of potency; while the presence of an aryl ester function at the 3-position was preferred to a thioester or an amide function to induce marked biological activity.This work confirms the interest of aryl esters of 6-substituted coumarin-3-carboxylic acids as potential new anticancer agents.

show abstract

Section: Introductionmentioning

confidence: 99%

6-Substituted 2-oxo-2H-1-benzopyran-3-carboxylic acid derivatives in a new approach of the treatment of cancer cell invasion and metastasis

Kempen

Hemmer

Counerotte

et al. 2008

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

show abstract

“…[6][7][8] Moreover, sunitinib has been known to inhibit the phosphorylation of colony-stimulating factor (CSF)-1R, resulting in the prevention of osteoclast function and CSF-1R-dependent osteolysis in an experimental breast cancer bone metastasis model. 9,10 These findings led us to propose the hypothesis that sunitinib may inhibit tumor growth and osteolysis in bone metastatic lesions in RCC patients.…”

mentioning

confidence: 99%

Antitumor effect of sunitinib against skeletal metastatic renal cell carcinoma through inhibition of osteoclast function

Maita

Yuasa

Tsuchiya

et al. 2011

Intl Journal of Cancer

View full text Add to dashboard Cite

We investigated the inhibitory effect of sunitinib, a newly approved multitargeted tyrosine kinase inhibitor, against the progression of renal cell cancer (RCC) bone metastases in vivo. In vitro cell proliferation was determined using the MTS assay. To investigate the inhibitory effects of sunitinib in vivo, we established luciferase-labeled ACHN Luc cells derived from papillary RCC. Mice in which ACHN Luc cells had been transplanted into the left ventricle to establish bone metastases were treated orally with 40 mg/kg/day sunitinib or vehicle control for 3 weeks. Growth of the cancer cells was monitored using an in vivo imaging system. In addition, 16 patients with metastatic RCC were treated with sunitinib, and serum and urine levels of amino-terminal telopeptide (NTx) were measured as markers of bone resorption. Sunitinib did not inhibit the growth of RCC cells in vitro at clinically or experimentally achievable serum levels (100 nM-1 lM). To investigate the inhibitory effect of sunitinib in vivo, we established luciferase-labeled human RCC cells (ACHN Luc ). Sunitinib prevented the growth of ACHN Luc RCC cells in the bone metastatic mouse model. The number of osteoclasts in sunitinib-treated mice was significantly less than that in control mice. Serum and urine levels of NTx in patients with metastatic RCC declined significantly during the first 4 weeks of sunitinib treatment (p 5 0.027). Sunitinib is a potent anticancer agent for RCC bone metastases, at least for papillary RCC.Bone is a common site of metastasis, with the frequency of solitary or multiple metastases to bone ranging from 24 to 51% in patients with metastatic renal cell cancer (RCC). 1-3 Although bone metastasis is not an independent prognostic factor associated with poor survival, the prognosis of patients with bone metastasis is not favorable when they are treated with cytokines, with an average life expectancy of 8-16 months. [2][3][4] Moreover, bone metastases are associated with poor performance status due to intractable pain and pathological fractures. 5 Because treatment options for RCC patients with bone metastasis are limited, appropriate treatment strategies are desired.Sunitinib is a newly approved, multitarget, small-molecule tyrosine kinase inhibitor for the treatment of metastatic RCC. It inhibits various receptor tyrosine kinases, including vascular endothelial growth factor (VEGF) receptors 1, 2 and 3; stem cell factor receptor (KIT) and PDGF receptors a and b. 6-8 Moreover, sunitinib has been known to inhibit the phosphorylation of colony-stimulating factor (CSF)-1R, resulting in the prevention of osteoclast function and CSF-1R-dependent osteolysis in an experimental breast cancer bone metastasis model. 9,10 These findings led us to propose the hypothesis that sunitinib may inhibit tumor growth and osteolysis in bone metastatic lesions in RCC patients.Although establishing a treatment strategy for bone metastases from RCC is important for urologists, the assessment of inhibitory effects on the growth of bone metastases is oft...

show abstract

“…However, a Markov model was created to determine the MC of sunitinib as at the time of analysis sunitinib was not reimbursed in Mexico. Adverse event and survival rates from the pivotal sunitinib study by Motzer et al (2006) and the Demetri et al (2006) survival study were used to construct the model. Hypothetical IMSS reimbursement values were calculated to evaluate therapy cost.…”

mentioning

confidence: 99%

A pharmaco-economic analysis of second-line treatment with imatinib or sunitinib in patients with advanced gastrointestinal stromal tumours

Contreras-Hernández

Mould-Quevedo²,

Silva

et al. 2008

Br J Cancer

View full text Add to dashboard Cite

Second-line treatments recommended by the National Cancer Center Network to manage advanced-stage gastrointestinal stromal tumours (GIST) were evaluated to determine the cost and cost-effectiveness of each intervention in the Mexican insurance system, the Instituto Mexicano del Seguro Social (IMSS). Treatments examined over a 5-year temporal horizon to estimate long-term costs included 800 mg day À1 of imatinib mesylate, 50 mg day À1 of sunitinib malate (administered in a 4 week on/2 week rest schedule), and palliative care. The mean cost (MC), cost-effectiveness, and benefit of each intervention were compared to determine the best GIST treatment from the institutional perspective of the IMSS. As sunitinib was not reimbursed at the time of the study, a Markov model and sensitivity analysis were conducted to predict the MC and likelihood of reimbursement. Patients taking 800 mg day À1 of imatinib had the highest MC ( ± s.d.) of treatment at $35 225.61 USD ( ± 1253.65 USD); while sunitinib incurred a median MC of $17 805.87 USD (±694.83 USD); and palliative care had the least MC over treatment duration as the cost was $2071.86 USD (±472.88 USD). In comparison to palliative care, sunitinib is cost-effective for 38.9% of patients; however, sunitinib delivered the greatest survival benefit as 5.64 progression-free months (PFM) and 1.4 life-years gained (LYG) were obtained in the economic model. Conversely, patients on imatinib and palliative care saw a lower PFM of 5.28 months and 2.58 months and also fewer LYG (only 1.31 and 1.08 years, respectively). Therefore, economic modeling predicts that reimbursing sunitinib over high dose imatinib in the second-line GIST indication would deliver cost savings to the IMSS and greater survival benefits to patients.

show abstract

Sunitinib malate for the treatment of solid tumours: a review of current clinical data

Cited by 112 publications

References 44 publications

6-Substituted 2-oxo-2H-1-benzopyran-3-carboxylic acid derivatives in a new approach of the treatment of cancer cell invasion and metastasis

6-Substituted 2-oxo-2H-1-benzopyran-3-carboxylic acid derivatives in a new approach of the treatment of cancer cell invasion and metastasis

Antitumor effect of sunitinib against skeletal metastatic renal cell carcinoma through inhibition of osteoclast function

A pharmaco-economic analysis of second-line treatment with imatinib or sunitinib in patients with advanced gastrointestinal stromal tumours

Contact Info

Product

Resources

About