Phase I/II study of capecitabine and PHY906 in hepatocellular carcinoma

Abstract

4610 PHY906, a Chinese medicine formula, has been used for 1,700 years for the treatment of diarrhea, vomiting, nausea, stomach cramps, and fever. PHY906 was found to potentiate the antitumor efficacy of capecitabine in hepatocellular carcinoma (HCC) xenografts. A Phase I/II, multicenter, open-label, dose-escalation, safety and efficacy study of capecitabine / PHY906 was initiated in patients with advanced HCC. Patients were required to have measurable, recurrent, metastatic, or unresectable HCC, Karnofsky status of 70% or above, and adequate organ and hematologic parameters. Study objectives were: Phase I - to determine the safety and tolerability of the two-drug combination; Phase II - to measure antitumor response and to assess patients’ quality of life (QoL). Patients were considered evaluable after two cycles of treatment. The initial dose regimen (capecitabine 1,000 mg/m2 BID; PHY906 1,000 mg BID) was found to have unfavorable toxicities. Thus, capecitabine was reduced to 750 mg/m2 BID and PHY906 to 600 mg BID. Subsequently, a new cohort of 750 mg/m2 BID capecitabine plus 800 mg BID PHY906 was added. Both latter regimens were well tolerated (N=4 for PHY906 600 mg BID, N=26 for PHY906 800 mg BID). The capecitabine 750 mg/m2 BID and PHY906 800 mg BID regimen was used for the Phase II study. Thirty-four patients participated in the Phase II study; 31 at US sites and 3 at Taiwan sites. Among the 27 evaluable patients at US sites, four (14.8%) achieved minor response (MR), 14(51.9%) had stable disease (SD), and 9(33.3%) exhibited progressive disease after two cycles of treatment. Median survival time was higher for the 20 Child-Pugh A patients (10.9 months vs. 9.2 months overall). Asian patients (N=12) had a higher overall 12-month survival rate (68%) than non-Asians (26%, N=15)[p=0.02]. Patients’ QoL did not appear to deteriorate significantly during treatment. Based on the results obtained with Child-Pugh A patients, additional Phase II studies in such patients in which the effectiveness of the capecitabine / PHY906 combination is compared to that of sorefinib (recently approved for the treatment of HCC) appear warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration PhytoCeutica Inc. PhytoCeutica Inc. PhytoCeutica Inc.