Phase I study of capecitabine combined with radioembolization using yttrium-90 resin microspheres (SIR-Spheres) in patients with advanced cancer.

BACKGROUND

This was a prospective single-centre, phase I study to document the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended phase II dose for future study of capecitabine in combination with radioembolization.

METHODS

Patients with advanced unresectable liver-dominant cancer were enrolled in a 3+3 design with escalating doses of capecitabine (375-1000 mg/m(2) b.i.d.) for 14 days every 21 days. Radioembolization with (90)Y-resin microspheres was administered using a sequential lobar approach with two cycles of capecitabine.

RESULTS

Twenty-four patients (17 colorectal) were enrolled. The MTD was not reached. Haematologic events were generally mild. Common grade 1/2 non-haematologic toxicities included transient transaminitis/alkaline phosphatase elevation (9 (37.5%) patients), nausea (9 (37.5%)), abdominal pain (7 (29.0%)), fatigue (7 (29.0%)), and hand-foot syndrome or rash/desquamation (7 (29.0%)). One patient experienced a partial gastric antral perforation with a capecitabine dose of 750 mg/m(2). The best response was partial response in four (16.7%) patients, stable disease in 17 (70.8%) and progression in three (12.5%). Median time to progression and overall survival of the metastatic colorectal cancer cohort was 6.4 and 8.1 months, respectively.

CONCLUSIONS

This combined modality treatment was generally well tolerated with encouraging clinical activity. Capecitabine 1000 mg/m(2) b.i.d. is recommended for phase II study with sequential lobar radioembolization.