SUTENT- sunitinib malate capsule
Pfizer Laboratories Div Pfizer Inc
WARNING: HEPATOTOXICITY
Hepatotoxicity has been observed in clinical trials and post-marketing experience. This hepatotoxicity may be severe, and deaths have been reported. [See Warnings and Precautions (5.1)]
1 INDICATIONS AND USAGE
1.1 Gastrointestinal Stromal Tumor (GIST)
SUTENT is indicated for the treatment of gastrointestinal stromal tumor after disease progression on or intolerance to imatinib mesylate.
1.2 Advanced Renal Cell Carcinoma (RCC)
SUTENT is indicated for the treatment of advanced renal cell carcinoma.
1.3 Advanced Pancreatic Neuroendocrine Tumors (pNET)
SUTENT is indicated for the treatment of progressive, well-differentiated pancreatic neuroendocrine tumors in patients with unresectable locally advanced or metastatic disease.
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dose for GIST and RCC
The recommended dose of SUTENT for gastrointestinal stromal tumor (GIST) and advanced renal cell carcinoma (RCC) is one 50 mg oral dose taken once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off (Schedule 4/2). SUTENT may be taken with or without food.
2.2 Recommended Dose for pNET
The recommended dose of SUTENT for pancreatic neuroendocrine tumors (pNET) is 37.5 mg taken orally once daily continuously without a scheduled off-treatment period. SUTENT may be taken with or without food.
2.3 Dose Modification
Dose interruption and/or dose modification in 12.5 mg increments or decrements is recommended based on individual safety and tolerability. The maximum dose administered in the Phase 3 pNET study was 50 mg daily.
DOSAGE FORMS AND STRENGTHS
12.5 mg capsules Hard gelatin capsule with orange cap and orange body, printed with white ink �Pfizer" on the cap and �STN 12.5 mg" on the body.
25 mg capsules Hard gelatin capsule with caramel cap and orange body, printed with white ink �Pfizer" on the cap and �STN 25 mg" on the body.
37.5 mg capsules
Hard gelatin capsule with yellow cap and yellow body, printed with black ink �Pfizer" on the cap and �STN 37.5 mg" on the body.
50 mg capsules
Hard gelatin capsule with caramel top and caramel body, printed with white ink �Pfizer" on the cap and �STN 50 mg" on the body.
DESCRIPTION
SUTENT, an oral multi-kinase inhibitor, is the malate salt of sunitinib. Sunitinib malate is described chemically as Butanedioic acid, hydroxy-, (2S)-, compound with N -[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-1,2-dihydro-2-oxo-3H -indol-3-ylidine)methyl]-2,4-dimethyl-1H -pyrrole-3-carboxamide (1:1). The molecular formula is C22 H27 FN4 O2 ? C4 H6 O5 and the molecular weight is 532.6 Daltons.
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Sunitinib is a small molecule that inhibits multiple receptor tyrosine kinases (RTKs), some of which are implicated in tumor growth, pathologic angiogenesis, and metastatic progression of cancer. Sunitinib was evaluated for its inhibitory activity against a variety of kinases (>80 kinases) and was identified as an inhibitor of platelet-derived growth factor receptors (PDGFR? and PDGFR?), vascular endothelial growth factor receptors (VEGFR1, VEGFR2 and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3), colony stimulating factor receptor Type 1 (CSF-1R), and the glial cell-line derived neurotrophic factor receptor (RET). Sunitinib inhibition of the activity of these RTKs has been demonstrated in biochemical and cellular assays, and inhibition of function has been demonstrated in cell proliferation assays. The primary metabolite exhibits similar potency compared to sunitinib in biochemical and cellular assays.
Sunitinib inhibited the phosphorylation of multiple RTKs (PDGFR?, VEGFR2, KIT) in tumor xenografts expressing RTK targets in vivo and demonstrated inhibition of tumor growth or tumor regression and/or inhibited metastases in some experimental models of cancer. Sunitinib demonstrated the ability to inhibit growth of tumor cells expressing dysregulated target RTKs (PDGFR, RET, or KIT) in vitro and to inhibit PDGFR?- and VEGFR2-dependent tumor angiogenesis in vivo.
