Sunitinib malate which is also known as Sutent is a medication that acts as a tyrosine kinase inhibitor with multiple targets on kidney cancer cells cells. Sunitinib has been shown to be a potent inhibitor of VEGF receptors, FLT3, c-KIT, and PDGF receptors. These targets give Sunitinib direct antitumor and antiangiogenic properties. The recommended dosing schedule for kidney cancer is 50 mg daily orally for 4 weeks, followed by 2 weeks off treatment (6-week cycles). Sunitinib can be taken with or without food.
Sunitinib’s efficacy was initially evaluated as second-line therapy for patients with a after having had their kidney removed (cytoreductive nephrectomy) and after failing cytokine treatment for kidney cancer. In two studies performed in 2006 and 2007, 169 patients were enrolled. Both trials demonstrated that Sunitinib has a positive response for kidney cancer in a second-line setting. In these studies, the response rates were 40% and 33%, and progression-free survival of 8.7 and 8.8 months was documented.
The positive results noted with Sunitinib in the second-line setting for metastatic kidney cancer led to an evaluation of Sunitinib comparing it to interferon as a first-line therapy. The results of this trial were published in the New England Journal of Medicine in 2007 and demonstrated that Sunitinib had a significant advantage in objective response rate (RR; 31% vs 6%) and in progression-free survival (11 months vs. 5 months) compared to interferon therapy. Sunitinib-treated patients had a median overall survival of 26.4 months versus 21.8 months for interferon treated patients.
The above image demonstrates relative progression-free survival (survival with the kidney cancer disease totally stable) of patients with metastatic kidney cancer taking Sutent vs. interferon alpha. The separation of the curves from 1 to 11 months demonstrates that patients who received Sutent had a longer period on average without progression of their metastatic kidney cancer than patients who received interferon alpha. Importantly, the lines come together again between 11 and 12 months, demonstrating that Sutent can increase the amount of time patients will live with metastatic kidney cancer before it gets worse. The differences noted in this study are probably even more pronounced than the results appear as patients who were not doing well on the interferon treatment were switched over to Sunitinib. Results of this study proved the superiority of Sunitinib over IFN-a as first-line treatment for patients with metastatic conventional kidney cancer.
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Adverse Effects (see table):
Adverse events that occurred with Sunitinib treatment included gastrointestinal events (diarrhea, nausea, mucositis, vomiting, dyspepsia, abdominal pain, gastroesophageal reflux, oral pain, glossodynia, and flatulence); bleeding; hypertension; dermatologic events (rash, skin discoloration, dry skin, and hair color changes); hand-foot syndrome; limb pain; decreases in heart function (ejection fraction); and peripheral swelling (edema). Diminishment of thyroid gland function (hypothyroidism) was also more common in patients receiving Sunitinib.
Serious (Grade 3/4 adverse events) side effects more common on Sunitinib included hypertension, diarrhea, hand-foot syndrome, nausea, vomiting, mucositis and bleeding. More common serious (grade 3/4) laboratory abnormalities in Sunitinib-treated patients included blood level problems (neutropenia, thrombocytopenia, and leucopenia), increased in pancrease enzymes (lipase and increased amylase), low blood sodium (hyponatremia), Calcium (hyperuricemia), and elevated levels of bilirubin in the blood (hyperbilirubinemia).
Adverse Effects |
All Grades |
Grade 3 or (%) |
Fatigue/Asthenia |
58 |
7 |
Diarrhea |
53 |
5 |
Nausea |
44 |
3 |
Vomiting |
24 |
4 |
Anorexia |
28 |
1 |
Abdominal Pain |
22 |
3 |
Hypertension |
24 |
8 |
Mucositis/Stomatitis |
45 |
3 |
Hand-Foot Syndrome |
20 |
5 |
Rash |
19 |
2 |
Skin discoloration |
16 |
0 |
Bleeding |
26 |
<1 |
Labaratory |
Neutropenia |
72 |
12 |
Anemia |
71 |
4 |
Hypophoshatemia |
36 |
5 |
Thrombocytopenia |
65 |
8 |
Hyperglycemia |
18 |
4 |
Elevated lipase |
52 |
16 |
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