Administration of Tivozanib via Gastrostomy Tube: A Pharmacokinetic Analysis

BACKGROUND

Tivozanib is an oral multikinase inhibitor targeting VEGFR-1,-2, and 3; c-KIT; and PDGFR-b. In the phase 3 TIVO-3 trial, tivozanib improved median progression-free survival (5.6 vs 3.9 months) over sorafenib, leading to FDA approval for adult patients with relapsed or refractory advanced renal cell carcinoma (RCC). To our knowledge, there are no published data on administering tivozanib through enteral tubes.

METHODS

The patient was unable to swallow pills due to a metastasis to his paratracheal lymph node, requiring tracheostomy tube placement. Tivozanib was dosed per the package insert. The capsule contents were mixed in whole milk, then administered via gastrostomy tube (G-tube) and subsequently flushed with at least 10 mL of whole milk. Patient whole-blood samples were collected through an outpatient lab or home health. Sample times were selected to capture maximum concentration (Cmax), trough (Ctrough), and terminal elimination (Celim) at steady state. Samples for C max were collected on day 14, at 6, 8, and 10 hours post dose, with Ctrough samples collected on days 15 and 18, prior to medication administration. Terminal elimination samples were collected during the off-treatment week. Samples were processed: centrifuged, plasma aliquoted, and stored at –80 °C. All samples were shipped for bioanalytical testing using a modified high-performance liquid chromatography-tandem mass spectrometry assay.

RESULTS

A total of 7 samples were collected, with all samples processed within 5 hours of collection. An 8-hour Cmax of 48.5ng/mL, Ctrough values of 54.8 and 34.3 ng/mL, and terminal elimination values of 40.8 and 22.7 ng/mL on days 23 and 25 were comparable to published values (Figure). The Ctrough collected on day 15 (concentration of 54.8 ng/mL) may have been drawn post dose and was subsequently left out of pharmacokinetic analyses. Radiographically, the hypopharyngeal mass decreased in size at month 2 and remained stable after month 4, while pulmonary nodules showed disease stability. Clinically, the patient experienced improved neck fullness, denied respiratory symptoms, and tolerated treatment well without significant adverse events or G-tube obstruction.

CONCLUSIONS

These findings suggest that tivozanib administered via G-tube can achieve pharmacokinetic exposure comparable to published data, resulting in clinically meaningful disease control with good tolerability. This may provide an alternative for patients unable to swallow tivozanib capsules.