Effect van een zoutbeperkt dieet op de bloeddrukstijging die door behandeling met sunitinib of regorafenib kan ontstaan
Subtitel:
Preventie van bijwerkingen vanVEGF-remmers door zoutbeperking (SUN-SALT studie)

Rationale: Growth and metastatic spread of a malignant tumor requires the formation of new blood vessels. Recent therapies target this mechanism by inhibiting vascular endothelial growth factor (VEGF)-signalling. Although this is an effective anticancer treatment, many patients develop cardiovascular side effects such as hypertension and kidney disease, frequently requiring dose reduction and/or early termination of treatment while still effective. Therefore, strategies to prevent VEGF inhibitor-induced toxicity are urgently needed.

In animal studies, VEGF inhibitor-induced hypertension is salt-sensitive. In this study, we want to study salt restriction in cancer patients treated with VEGF inhibitors sunitinib and regorafenib as a strategy to attenuate or prevent VEGF inhibitor-induced toxicity, primarily the rise in blood pressure.

Objective: To prospectively study the effect of salt restriction on the rise in blood pressure in response to anti-cancer treatment with the VEGF inhibitor sunitinib and regorafenib.

Study design: This is a single centre prospective open-label intervention study to compare a treatment cycle using salt restriction with the previous treatment cycle without salt restriction.

Study population: Patients treated with sunitinib or regorafenib according to standard of care, using a standard dosing regimen.

Intervention: A salt restricted diet (<4 grams/day) will be started during the off-treatment period under guidance of a specialized dietititan. Salt-less bread will be provided. The whole period of salt restriction will take four (regorafenib) or five (sunitinib) weeks.

Main study parameters/endpoints: Primary endpoint: mean difference in blood pressure rise between the treatment cycle with and the treatment cycle without salt restriction.

Secondary endpoints: effects of salt restriction on rise in endothelin-1, proteinuria as marker for nephropathy and pharmacokinetics of sunitinib and regorafenib; if an effect on blood pressure is shown, further analyses of effects on renal transporter proteins will be performed to explain the mechanism of salt sensitivity.

Salt restriction is an effective strategy to attenuate or prevent VEGF inhibitor-induced toxicity, primarily the rise in blood pressure.

The last endpoint is at the end of treatment cycle with regorafenib or sunitinib in which the salt restriction was applied

Salt restricted (<4g/day) diet