Phase I/II study of transcatheter arterial chemoembolization with cisplatin powder and degradable starch microspheres for unresectable hepatic metastases from colorectal cancer refractory to systemic standard chemotherapy.

Abstract

577 Background: We conducted a phase I/II study of novel transcatheter arterial chemoembolization with cisplatin powder and degradable starch microspheres (DSM) to determine the recommended dose (RD) and to assess the efficacy and safety. Methods: Cisplatin powder and DSM mixing solution was administered followed by the injection of DSM alone via hepatic artery every 4 weeks. In phase I, cohorts of 3 patients received escalating dose of cisplatin (50, 65 and 80mg/m2), and RD was estimated during the first cycle. In the phase II, more RD patients were added to assess tumor response, toxicity, hepatic progression free survival (H-PFS) and 6-month overall survival (OS) rate. Results: A total of 24 patients (male 16, female 8; mean age 63.0, range 45-79; colon 15, rectal 9) were enrolled in this study. FOLFOX had previously been administered to all patients, irinotecan-containing regimen to 12 and bevacizumab and/or cetuximab to 14. During phase I (n= 9 patients), maximum tolerated dose was not reached and cisplatin 80 mg/m2 was recommended for a phase II. Phase II enrolled 15 patients. The following grade 3 toxicities were observed: platelets reduction 16.6%, aspartate transaminase elevation 38.8%, alanine transaminase elevation 16.6%, hyponatremia 11.1%, cholecystitis 5.5%. The tumor response rate was 53.3% (CR 0, PR 8, SD 6, and PD 1). The median H-PFS was 6.3 months (95% CI; 2.71 to 9.88) and 6 -month OS rate was 86.7%. Conclusions: This phase I/II study demonstrates that novel transcatheter arterial chemoembolization with 80 mg/m2 cisplatin powder and DSM is well tolerable, and can produce a high response rate with encouraging survival duration. Further clinical trials are warranted. No significant financial relationships to disclose.