Sutent |
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SUTENT is a medicine that treats 2 kinds of cancer.
1. GIST (gastrointestinal stromal tumor). This is a rare cancer of the stomach, bowel, or esophagus. SUTENT is used when the medicine
Gleevec® (imatinib mesylate) did not stop the cancer from growing OR
when you cannot take Gleevec®.
2. Advanced kidney cancer (advanced renal cell carcinoma or RCC). SUTENT may slow or stop the growth of cancer. It may help shrink tumors. SUTENT has not been studied in children.
Key phrases: sutent Pfizer, sutent cost, sunitinib malate, sunitinib sutent, sunitinib breast cancer, sunitinib clinical trials.
| Dosage |
Packing |
Price |
Add to basket |
| 12.5 mg |
28 caps |
USD 1900.00 |
 |
| 25 mg |
28 caps |
USD 4500.00 |
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| 50 mg |
28 caps |
USD 7900.00 |
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Sutent generic (generic - what is it?)
| Dosage |
Packing |
Price |
Add to basket |
| 12.5 mg |
28 caps |
USD 1250.00 |
|
| 25 mg |
10 caps |
USD 960.00 |
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| 50 mg |
28 caos |
USD 4290.00 |
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Sutent: Medications and Prescriptions
Generic name: sunitinib
Product Manufacturer: Pfizer
Sutent description
Sunitinib (marketed as Sutent, and previously known as SU11248) is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) on January 26, 2006. Sunitinib was the first cancer drug simultaneously approved for two different indications. [1] Sunitinib has become a standard of care for both of these cancers, and is currently being studied for the treatment of many others.
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.
Renal cell carcinoma:
Sunitinib is a standard of care in the first-line treatment of metastatic RCC, other therapeutic options in this setting are sorafenib (Nexavar), temsirolimus (Torisel) and interleukin-2 (Proleukin).
RCC is generally resistant to chemotherapy or radiation. Prior to RTKs, metastatic disease could only be treated with the cytokines interferon alpha (IFNα) or Interleukin 2 (IL-2). However, these agents demonstrated low rates of efficacy (5%-20%).
In two separate Phase II studies, sunitinib demonstrated consistent response rates of approximately 40% in patients who had already failed cytokine therapy. [7] Although these were Phase II studies, these results were impressive enough for the FDA to approve sunitinib for first-line use even before Phase III data were available.
The results of the Phase III study, published in the New England Journal of Medicine in 2007, proved that sunitinib offers superior efficacy compared with IFNα. Progression-free survival (primary endpoint) was more than doubled: 11 months for sunitinib compared with 5 months for IFNα (P<.000001). The benefit for sunitinib was significant across all major patient subgroups, including those with a poor prognosis at baseline.
Secondary endpoints also favored sunitinib. 28% of sunitinib patients had significant tumor shrinkage (objective response) compared with only 5% of patients who received IFNα (P<.001). Although overall survival data are not yet mature, there is a clear trend toward improved survival with sunitinib. Patients receiving sunitinib also reported a significantly better quality of life than those treated with IFNα (P<.001). Based on these results, lead investigator Dr. Robert Motzer announced at ASCO 2006 that “Sunitinib is the new reference standard for the first-line treatment of mRCC.”
RCC: update
At ASCO 2008, Dr Robert Figlin presented updated data from the final study analysis, including overall survival. The primary endpoint of median PFS remained superior with sunitinib: 11 months versus 5 months for IFNα, P<.000001. Objective response rate also remained superior: 39-47% for sunitinib versus 8-12% with IFNα, P<.000001.
Sunitinib was associated with somewhat longer overall survival, although this was not statistically significant. Median OS was 26 months with sunitinib vs 22 months for IFNα regardless of stratification (P-value ranges from .051 to .0132, depending on statistical analysis). The first analysis includes 25 patients initially randomized to IFNα who crossed over to sunitinib therapy, which may have confounded the results; in an exploratory analysis that excluded these patients, the difference is becomes more robust: 26 vs 20 months, P=.0081. Patients in the study were allowed to receive other therapies once they had progressed on their study treatment. For a “pure” analysis of the difference between the two agents, an analysis was done using only patients who did not receive any post-study treatment. This analysis demonstrated the greatest advantage for sunitinib: 28 months vs 14 months for IFNα, P=.0033. The number of patients in this analysis was small and this does not reflect actual clinical practice and is therefore not meaningful.
Also worth noting in this presentation was the fact that the updated percentage of patients that had to discontinue sunitinib due to adverse events was 19%. This is a clinically meaningful number.
This was the largest comparative trial in RCC to date, and sunitinib is the first agent to demonstrate an overall survival longer than 2 years in these patients. Dr. Figlin concluded his presentation by reinforcing that “Sunitinib is the reference standard for the first-line treatment of mRCC.”
Gastrointestinal stromal tumor
Like RCC, GIST does not generally respond to standard chemotherapy or radiation. Imatinib was the first cancer agent proven effective for metastatic GIST and represented a major development in the treatment of this rare but challenging disease. However, approximately 20% of patients do not respond to imatinib (early or primary resistance), and among those who do respond initially, 50% develop secondary imatinib resistance and disease progression within 2 years. Prior to sunitinib, patients had no therapeutic option once they became resistant to imatinib.
Sunitinib offers patients with imatinib-resistant GIST a new treatment option to stop further disease progression and, in some cases, even reverse it. This was proven in a large, Phase III clinical trial in which patients who failed imatinib therapy (due to primary resistance, secondary resistance, or intolerance) were treated in a randomized and blinded fashion with either sunitinib or placebo.
The study was unblinded early, at the very first interim analysis, due to the clearly emerging benefit of sunitinib. At that time, patients receiving placebo were offered to switch over to sunitinib. In the primary endpoint of this study, median time to tumor progression (TTP) was more than 4-fold longer with sunitinib (27 weeks) compared with placebo (6 weeks, P<.0001). These are based on the assessments of an independent radiology lab assessment. The benefit of sunitinib remained statistically significant when stratified for a multitude of prespecified baseline factors, including: Prior dose of imatinib, Prior duration of imatinib therapy, ECOG Performance status, Age, Weight, Race, Pain score, Time since initial diagnosis, Study location, ITT vs PP analysis,
Investigator vs independent radiology lab assessment.
Among the secondary endpoints, the difference in PFS was similar to that in TTP (24 weeks vs 6 weeks, P<.0001). 7% of sunitinib patients had significant tumor shrinkage (objective response) compared with 0% of placebo patients (P=.006). Another 58% of sunitinib patients had disease stabilization vs. 48% of patients receiving placebo. The median time to response with sunitinib was 10.4 weeks. Sunitinib reduced the relative risk of disease progression or death by 67%, and the risk of death alone by 51%. The difference in survival benefit may be diluted by the fact that placebo patients crossed over to sunitinib upon disease progression, and most of these patients subsequently responded to sunitinib.
Sunitinib was relatively well tolerated. 83% of sunitinib patients experienced a treatment-related adverse event of any severity, as did 59% of patients who received placebo. Serious adverse events were reported in 20% of sunitinib patients and 5% of placebo patients. Adverse events were generally moderate and easily managed by dose reduction, dose interruption, or other treatment. 9% of sunitinib patients and 8% of placebo patients discontinued therapy due to an adverse event.
Fatigue is the adverse event most commonly associated with sunitinib therapy. In this study, 34% of sunitinib patients reported any grade of fatigue, compared with 22% for placebo. The incidence of grade 3 (severe) fatigue was similar between the two groups, and there was no grade 4 fatigue reported.
Other solid tumors
The efficacy of sunitinib is currently being evaluated in a broad range of solid tumors, including breast, lung, and colorectal cancers. Early studies have shown single-agent efficacy in a number of different areas. In addition to blocking angiogenesis, Sutent® also inhibits additional enzymes that are involved in the development of tumours. The discovery of the drug and clarification of the multi-specific mechanism of action is based on discoveries of Axel Ullrich and his team at the Max Planck Institute of Biochemistry in the 1980s in Munich. Medical and pharmaceutical development as well as clinical testing of the drug was carried out by Sugen, a company founded in 1991 by Ullrich and his American colleague Joseph Schlessinger (the S in Sugen stands for Schlessinger, the U for Ullrich), also involving New York University and the Max Planck Society.The concept was of a ATP analogue that would compete with ATP for binding to the catalytic site of receptor tyrosine kinases. This concept led to the invention of an important small-molecule tyrosine kinase inhibitor called Sunitinib.
A Phase II study in previously-treated patients with metastatic breast cancer found that sunitinib “has significant single agent activity”
A Phase II study of refractory non-small-cell lung cancer found that “Sunitinib has provocative single-agent activity in previously treated pts with recurrent and advanced NSCLC, with the level of activity similar to currently approved agents.”
In a Phase II study of patients with nonresectable neuroendocrine tumors (NET), 91% of patients responded to sunitinib (9% partial response + 82% stable disease).
Side effects
Sunitinib has been generally well tolerated. Adverse events were considered somewhat manageable and the incidence of serious adverse events low.
The most common adverse events associated with sunitinib therapy are fatigue, diarrhea, nausea, anorexia, hypertension, a yellow skin discoloration, hand-foot skin reaction, and stomatitis. In the placebo-controlled Phase III GIST study, adverse events which occurred more often with sunitinib than placebo included diarrhea, anorexia, skin discoloration, mucositis/stomatitis, asthenia, altered taste, and constipation.
Dose reductions were required in 50% of the patients studied in RCC in order to manage the significant toxicities of this agent.
Serious (grade 3 or 4) adverse events occur in ≤10% of patients and include hypertension, fatigue, asthenia, diarrhea, and hand-foot syndrome. Lab abnormalities associated with sunitinib therapy include lipase, amylase, neutrophils, lymphocytes, and platelets. Hypothyroidism has also been associated with sunitinib.
Most adverse events can be managed through supportive care, dose interruption, or dose reduction.
The efficacy of the dose reduced sub-group has never been published.
Costs:
Sunitinib is marketed by Pfizer as Sutent, and is subject to patents and market exclusivity as a new chemical entity until February 15, 2021. Sutent has been cited in financial news as a potential revenue source to replace royalties lost from Lipitor following the expiration of the latter drug's patent expiration in November 2011.Sutent is one of the most expensive drugs widely marketed. Doctors and editorials have criticized the high cost, for a drug that doesn't cure cancer but only prolongs life.
What should you tell your doctor before taking SUTENT?
Tell your doctor about all your medical conditions. Be sure to tell your doctor if you:
• are pregnant, could be pregnant, or plan to get pregnant. SUTENT may harm
an unborn baby.
• are breast-feeding. Do not breast-feed while you are being treated with SUTENT.
• have any heart problems
• have high blood pressure
• have kidney function problems (other than cancer)
• have liver problems
• have any bleeding problem
• have seizures
SUTENT and other medicines:
Tell your doctor about all your medicines. Include prescription medicines, overthecounter drugs, vitamins, and herbal products. Some medicines can react with SUTENT and cause serious side effects.
Especially tell your doctor if you take:
• St. John’s Wort. Do not take St. John’s Wort while taking SUTENT.
• Dexamethasone (a steroid)
• Medicine for:
• tuberculosis (TB) • seizures (epilepsy)
• infections (antibiotics) • fungal infections (antifungals)
• depression • HIV (AIDS)
Keep a list of your medicines. Show it to your doctor or pharmacist. Talk with your doctor before starting any new medicines.
What are possible side effects of SUTENT?
Possible serious side effects include:
• Heart Problems. Tell your doctor if you feel very tired, are short of breath, or have swollen feet and ankles.
• Rare life-threatening events: hole in stomach or bowel wall (perforation) or bleeding from the tumor. Both of these side effects could cause symptoms such as painful, swollen abdomen, vomiting blood, and black, sticky stools. Your doctor can tell you other symptoms to watch for.
• Increased blood pressure. Your doctor may check your blood pressure. You may need treatment for high blood pressure.
Common side effects:
• Feeling tired
• Diarrhea, nausea, vomiting, mouth sores, upset stomach, abdominal pain, and constipation. Talk with your doctor about ways to handle these problems.
• The medicine in SUTENT is yellow, so it may make your skin look yellow. Your skin and hair may get lighter.
• Your skin may become dry, get thicker, or crack. You may get blisters or a rash on the palms of your hands and soles of your feet.
• Taste changes • Swelling
• Loss of appetite • High blood pressure
• Bleeding, such as nosebleeds or bleeding from cuts. Call your doctor if you have any swelling or bleeding.
There are other side effects. For a more complete list, ask your cancer specialist nurse or doctor.
How Supplied
12.5 mg Capsules
Hard gelatin capsule with orange cap and orange body, printed with white ink "Pfizer" on the cap, "STN 12.5 mg" on the body; available in: Bottles of 28
25 mg Capsules
Hard gelatin capsule with caramel cap and orange body, printed with white ink "Pfizer" on the cap, "STN 25 mg" on the body; available in:
Bottles of 28:
50 mg Capsules
Hard gelatin capsule with caramel cap and caramel body, printed with white ink "Pfizer" on the cap, "STN 50 mg" on the body; available in:
Bottles of 28:
Storage:
Store at 25oC (77oF); excursions permitted to 15-30oC (59-86oF)
How should I take SUTENT?
• SUTENT comes in 12.5 mg, 25 mg, and 50 mg capsules you take by mouth. Do not open the capsules.
• Take SUTENT once a day with or without food.
• Take it exactly the way your doctor tells you.
• Do not drink grapefruit juice or eat grapefruit. They may change the amount of SUTENT in your body.
• Dosing cycle:
• Take SUTENT for 4 weeks (28 days) THEN
• Stop for 2 weeks (14 days)
• Repeat this cycle as long as your doctor tells you
• Your doctor may check your blood before each dosing cycle.
• If you miss a dose, take it as soon as you remember. Do not take it if it is close to your next dose. Just take the next dose at your regular time. Do not take more than 1 dose of SUTENT at a time. Tell your doctor or nurse about the missed dose.
• Call your doctor right away, if you take too much SUTENT.
What is in SUTENT?
Active ingredient: sunitinib malate
Inactive ingredients: mannitol, croscarmellose sodium, povidone (K-25), magnesium stearate Orange gelatin capsule shell: titanium dioxide, red iron oxide Caramel gelatin capsule shell: yellow iron oxide, black iron oxide Printing ink: shellac, propylene glycol, sodium hydroxide, povidone, titanium dioxide.
See also: Bowel and Stomach cancer
Sutent notes:
Sutent generic name sunitinib available under name of Pfizer is used to treat certain types of advanced or progressive tumors of the digestive system or the kidneys. It helps the body by slowing down the growth and reproduction of tumor cells.
Sunitinib malate of the group antineoplastics medicnes, is used to treat patients with gastrointestinal stromal tumor which develops in wall of stomach, intestine or rectum, when the medicine imatinib mesylate did not stop the cancer from growing or when the patient cannot take imatinib mesylate.
Sunitinibis used to treat triple negative tumours i.e. breast cancers that do not contain growth regulator proteins for estrogen and progesterone receptor. Patients with such type of tumors have a poor prognosis when treated with standard therapies. It works by blocking angiogenesis which is the process of new blood vessel growth in tumors.
According to clinical trial, sunitinib patients lived for a median of 26.4 months, compared with 21.8 months for Interferons(IFN) patients. Tumors shrank in 31 percent of sunitinib patients, compared with six percent of IFN.
Store sunitinib at room temperature away from moisture and heat.
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Drug category:Anti-cancer drugs
 Sutent
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