A phase I study of capecitabine in combination with yttrium-90 labeled resin microspheres (SIR-Spheres) in patients (pts) with advanced cancer.

Abstract

e14612 Background: Radioembolization (RE) with Yttrium-90 labeled resin microspheres (SIR-Spheres) is an emerging treatment for liver tumors, both alone and with chemotherapy. Concurrent use of capecitabine (cape) with RE has been contraindicated due to concerns for liver toxicity. This phase I study was initiated to formally evaluate the safety of concurrent cape and RE. Methods: Pts with unresectable metastatic or primary liver tumors were treated in a 3+3 design with escalating doses of cape (375, 600, 750, 900 mg/m2) bid x 14d q21d. RE was performed on the dominant diseased liver lobe on day 2 of chemotherapy. Repeat imaging was obtained after 2 cycles of cape. Pts with bilobar disease without progression in the treated lobe could receive a second RE with 2 additional cycles of cape. Inclusion criteria were liver only/dominant disease, any number of prior regimens, ECOG PS 0-1, bilirubin ≤ ULN, ALT and AST ≤ 1.5 x ULN, patent portal vein, < 20% lung shunt. Primary endpoints were safety and toxicity. Results: Pts (n=21) were enrolled in 4 cohorts. Pt characteristics: median age 61 (49-81), M/F (13/8), diagnoses (CRC 16, NET, biliary, HCC, small bowel, unknown, 1 each), median prior tx=2, prior TACE=2. Cohort 1 (375 mg/m2, n=8): Of the first 3, one pt with biliary cancer had gr 3 hyperbilirubinemia possibly related to tx. Of the next 2 pts, one with CRC had gr 4 hyperbilirubinemia related to disease. The cohort was expanded to 8 with no further DLTs. Cohort 2 (600 mg/m2, n=4 - one pt erroneously took 300 mg/m2 of cap): No DLTs were observed. Cohort 3 (750 mg/m2, n=6): One pt with mCRC and a large left lobe lesion had a partial antral perforation possibly related to tx and the cohort was expanded to 6, with no further DLTs. Cohort 4 (900 mg/m2, n=3): No DLTs were observed. No other gr 3/4 non-heme toxicities were noted. Common gr 1/2 non-heme toxicities included transaminitis/alk phos elevation (9), nausea (8), pain (7), fatigue (5), and hand/foot (5). Best response: cPR (3), uPR (1), SD (16), PD (1). Conclusions: Capecitabine can be safely administered with SIR-Spheres at doses typically utilized with combination chemotherapy (up to 900 mg/m2 twice daily). Further evaluation in CRC patients is planned.