From the Guidelines
The first step in reducing the dose of sunitinib (sunitinib malate) for a patient experiencing adverse effects is to decrease the dose from the standard 50 mg once daily to 37.5 mg once daily. This approach is based on the guidelines for managing toxicities caused by sunitinib malate, which suggest that dose interruptions or reductions can often manage sunitinib-related toxicities 1. The recommended dose of sunitinib is either 37.5 mg orally once daily without interruption or 50 mg orally once daily on a schedule of 4 weeks on treatment followed by 2 weeks off (schedule 4/2) 1.
When considering dose reduction, it's essential to balance the need for therapeutic efficacy while minimizing adverse effects. Sunitinib's mechanism as a multi-targeted tyrosine kinase inhibitor means its side effect profile includes fatigue, hypertension, hand-foot syndrome, diarrhea, and myelosuppression. Implementing dose reductions promptly when significant toxicities occur is crucial, as maintaining treatment at a lower dose is generally preferable to discontinuing therapy entirely.
Key considerations for dose modification include:
- Dose reduction to a minimum of 37.5 mg daily if sunitinib must be coadministered with a strong CYP3A4 inhibitor 1
- Dose increase to a maximum of 87.5 mg daily if sunitinib must be co-administered with a CYP3A4 inducer 1
- Selection of an alternate concomitant medication with no or minimal enzyme induction potential is recommended for patients receiving sunitinib 1
By following this stepwise approach to dose reduction, clinicians can effectively manage sunitinib-related toxicities while optimizing treatment outcomes for patients.
From the FDA Drug Label
To manage adverse reactions, the recommended dosage modifications are provided in Table 1. Table 1 Recommended Dosage Reductions of Sunitinib Malate Capsules for Adverse Reactions Indications GIST RCC pNET Advanced RCC Adjuvant RCC First dose reduction 37.5 mg once daily 37.5 mg once daily 37. 5 mg once daily 25 mg once daily
The first step in reducing the dose of Sunitinib for a patient experiencing adverse effects is to decrease the dose to 37.5 mg once daily for GIST, RCC, and pNET, and to 25 mg once daily for Advanced RCC Adjuvant 2.
From the Research
Sunitinib Dose Reduction
- The first step in reducing the dose of Sunitinib for a patient experiencing adverse effects is to assess the severity of the adverse effects and the patient's overall condition 3.
- Dose adjustments or interruptions may be necessary to manage toxicities, with the goal of finding a balance between efficacy and tolerability 3.
- In some cases, a dose reduction to 37.5 mg/day may be considered, as this dose has been shown to have a manageable safety profile and significant antitumor activity in patients with metastatic renal cell carcinoma 4.
- The decision to reduce the dose should be based on the individual patient's response to treatment and the severity of any adverse effects, with the aim of maintaining an optimal therapeutic effect while minimizing toxicity 5.
- Therapeutic drug monitoring (TDM) may be useful in optimizing sunitinib exposure and reducing the risk of toxicity, with higher sunitinib exposure associated with increased toxicity leading to dose reduction 6.
- Examples of dose reduction strategies include:
- Reducing the dose from 50 mg/day to 37.5 mg/day, as described in a phase II trial of continuous once-daily dosing of sunitinib as first-line treatment in patients with metastatic renal cell carcinoma 4.
- Escalating the dose after an initial reduction, as reported in a case study of a patient with gastrointestinal stromal tumor of the small intestine who experienced a partial response after dose escalation 7.