What is the administration route of Sunitinib (Sutent)?

From the Guidelines

Sunitinib is typically given orally in capsule form, with a standard dosing regimen of 50 mg once daily for 4 weeks, followed by a 2-week rest period, or continuous daily dosing of 37.5 mg without breaks for certain conditions. The most recent and highest quality study, published in 2022 1, supports the use of sunitinib as a second-line treatment for patients with gastrointestinal stromal tumors (GIST) who have progressed on or are intolerant to imatinib. The study recommends a dose of 50 mg daily following a "4 weeks on/2 weeks off" regimen, or a continuously dosed daily oral regimen with a lower daily dose of 37.5 mg.

Key Considerations

• Sunitinib should be taken with or without food consistently, meaning patients should establish a routine of either always taking it with food or always without.
• Dose adjustments may be necessary based on individual tolerability and side effects, which commonly include fatigue, diarrhea, skin discoloration, and hypertension.
• Regular monitoring of blood pressure, thyroid function, liver enzymes, and complete blood counts is essential during treatment.
• Sunitinib works as a multi-targeted tyrosine kinase inhibitor that blocks several proteins involved in tumor growth and angiogenesis, effectively cutting off the blood supply to tumors and inhibiting cancer cell growth.

Administration and Monitoring

• The dose and schedule of sunitinib may be individualized depending on patient response and adverse events, as noted in the 2016 study 1.
• Patients with metastatic GIST should be considered for participation in clinical trials of new therapies or combinations, as recommended in the 2022 study 1.
• The use of combinations of tyrosine kinase inhibitors (TKIs) outside of clinical studies should be discouraged due to the potential for considerable toxicity, as noted in the 2018 study 1.

Evidence-Based Recommendations

• The 2017 study 1 recommends sunitinib at 50 mg orally once a day over 4 weeks followed by a 2-week rest period as the therapy of choice after failure of imatinib.
• The 2022 study 1 supports the use of sunitinib as a second-line treatment for patients with GIST who have progressed on or are intolerant to imatinib, with a recommended dose of 50 mg daily following a "4 weeks on/2 weeks off" regimen, or a continuously dosed daily oral regimen with a lower daily dose of 37.5 mg.

From the FDA Drug Label

The pharmacokinetics of sunitinib and sunitinib malate have been evaluated in healthy subjects and in patients with solid tumors. Sunitinib AUC and C max increase proportionately over a dose range of 25 mg to 100 mg (0. 5 to 2 times the approved RDD of 50 mg). Following oral administration of sunitinib, the time to maximum plasma concentration (T max) ranged from 6 to 12 hours

• Administration: Sunitinib is given orally.
• Dosage form: Sunitinib malate capsules are supplied as printed hard shell capsules containing 12.5 mg, 25 mg, 37.5 mg or 50 mg of sunitinib.
• Key points: The administration of a single dose of sunitinib 50 mg with a high-fat, high-calorie meal had no clinically significant effect on sunitinib or active metabolites exposure 2

From the Research

Administration of Sunitinib

• Sunitinib is administered orally 3, 4, 5.
• The approved dose of sunitinib is 50 mg/d PO for 4 weeks, followed by a 2-week rest 4.
• This pattern is repeated until tumor progression or the occurrence of intolerable adverse effects 4.
• Sunitinib can also be administered on a continuous daily schedule at a lower dose 3.
• The dosage can be modulated (between 25 and 50 mg/day) and/or schedules (4 weeks on, 2 weeks off or continuous administration) to optimize the benefit-risk profile of sunitinib in individual patients 3.

Factors Affecting Sunitinib Administration

• Food does not appear to affect the bioavailability of sunitinib 4.
• Sunitinib is metabolized by cytochrome P450 (CYP) 3A4 to an active metabolite, SU12662 4.
• The parent compound and active metabolite have similar biochemical activity and potency and reach similar plasma concentrations 4.
• Steady-state concentrations of both active entities are reached after 10 to 14 days of therapy 4.

Therapeutic Drug Monitoring

• Therapeutic drug monitoring (TDM) of sunitinib and its major metabolite, N-desethylsunitinib, may be necessary to optimize treatment outcomes 5.
• A total (sunitinib + N-desethylsunitinib) trough level of 50-100 ng/mL serves as a reasonable target therapeutic range for optimal therapeutic response 5.
• To avoid toxicity, the total trough levels should not exceed 100 ng/mL 5.