Drug-Eluting Bead, Irinotecan Therapy of Unresectable Intrahepatic Cholangiocarcinoma (DELTIC) with Concomitant Systemic Gemcitabine and Cisplatin.

BACKGROUND: Unresectable intrahepatic cholangiocarcinoma (ICC) carries a poor prognosis, and currently there are moderately established chemotherapeutic [gemcitabine/cisplatin (Gem/Cis)] treatments to prolong survival. The purpose of this study was to assess the efficacy of irinotecan drug-eluting beads (DEBIRI) therapy by transarterial infusion in combination with systemic therapy in unresectable ICC. PATIENTS AND METHODS: This is a prospective, multicenter, open-label, randomized phase II study (Clin Trials: NCT01648023-DELTIC trial) of patients with ICC randomly assigned to Gem/Cis with DEBIRI or Gem/Cis alone. The primary endpoint was response rate. RESULTS: The intention-to-treat population comprised 48 patients: 24 treated with Gem/Cis and DEBIRI and 22 with Gem/Cis alone (2 screen failures). The two groups were similar with respect to the extent of liver involvement (35% versus 38%) and presence of extrahepatic disease (29% versus 14%, p = 0.12). Median numbers of chemotherapy cycles were similar (6 versus 6), as were rates of grade 3/4 adverse events (34% for the Gem/Cis-DEBIRI group versus 36% for the Gem/Cis group). The overall response rate was significantly greater in the Gem/Cis-DEBIRI arm versus the Gem/Cis arm at 2 (p < 0.04), 4 (p < 0.03), and 6 months (p < 0.05). There was significantly more downsizing to resection/ablation in the Gem/Cis-DEBIRI arm versus the Gem/Cis arm (25% versus 8%, p < 005), and there was improved median progression-free survival [31.9 (95% CI 8.5-75.3) months versus 10.1 (95% CI 5.3-13.5) months, p = 0.028] and improved overall survival [33.7 (95% CI 13.5-54.5) months versus 12.6 (95% CI 8.7-33.4) months, p = 0.048]. CONCLUSION: Combination Gem/Cis with DEBIRI is safe, and leads to significant improvement in downsizing to resection, improved progression-free survival, and overall survival.

Randomized controlled trial of irinotecan drug-eluting beads with simultaneous FOLFOX and bevacizumab for patients with unresectable colorectal liver-limited metastasis.

BACKGROUND: Reports have demonstrated the superior activity of combining both irinotecan and oxaliplatin (FOLFOXIRI) therapy. An option for gaining similar benefits with less toxicity would be the administration of irinotecan through a hepatic artery approach. The aim of this study was to assess the response and adverse event rates for irinotecan drug-eluting beads (DEBIRI) with folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX) and bevacizumab as a first-line treatment for unresectable colorectal liver metastasis. METHODS: Patients with colorectal liver metastases were randomly assigned to modified FOLFOX (mFOLFOX) and bevacizumab or mFOLFOX6, bevacizumab, and DEBIRI (FOLFOX-DEBIRI). The primary endpoint was the response rate. The secondary endpoints were adverse events, the rate of conversion to resection, and progression-free survival. RESULTS: The intention-to-treat population comprised 70 patients: 10 patients in the pilot and then 30 patients randomly assigned to the FOLFOX-DEBIRI arm and 30 patients randomly assigned to the FOLFOX/bevacizumab arm. The 2 groups were similar with respect to the extent of liver involvement (30% vs 30%), but a greater percentage of patients in the FOLFOX-DEBIRI arm had an Eastern Cooperative Oncology Group performance status of 1 or 2 (57% vs 31%) and extrahepatic disease (56% vs 32%, P = .02). The median numbers of chemotherapy cycles were similar (10 vs 9), and there were similar rates of grade 3/4 adverse events (54% for the FOLFOX-DEBIRI group vs 46% for the FOLFOX/bevacizumab group). The overall response rate was significantly greater in the FOLFOX-DEBIRI arm versus the FOLFOX/bevacizumab arm at 2 (78% vs 54%, P = .02), 4 (95% vs 70%, P = .03), and 6 months (76% vs 60%, P = .05). There was significantly more downsizing to resection in the FOLFOX-DEBIRI arm versus the FOLFOX/bevacizumab arm (35% vs 16%, P = .05), and there was improved median progression-free survival (15.3 vs 7.6 months). CONCLUSIONS: The simultaneous administration of mFOLFOX6 (with or without bevacizumab) and DEBIRI through the hepatic artery (FOLFOX-DEBIRI) is safe and does not cause treatment delays or increase the systemic toxicity of chemotherapy. This strategy leads to improved overall response rates, improved hepatic progression-free survival, and more durable overall progression-free survival in patients downsized to resection.

Is selective internal radioembolization safe and effective for patients with inoperable hepatocellular carcinoma and venous thrombosis?

BACKGROUND: The goal of this study was to examine the safety and efficacy of selective internal radioembolization (SIR) for hepatocellular carcinoma (HCC) with portal vein or caval thrombosis (VT), or both. Recent reports have demonstrated that SIR is safe for patients with HCC, but the impact on efficacy of venous thrombosis is unknown. STUDY DESIGN: Prospective single-arm study of the use of Therasphere in patients with unresectable HCC enrolled from January 2004 to June 2007. Patients were categorized into three groups based on VT status and therapy. RESULTS: Fifty-two patients were enrolled: 20 patients without VT who received SIR, 15 patients with VT who were treated, and 17 patients (10 with VT) who were not treated because of preprocedure screening failure. Fifty-eight treatments were administered, with a median of two treatments per patient (range of one to three treatments). Child's score was different between groups. Of the VT patients treated, 67% had portal VT, 7% had cava VT, and 26% had both. There were no treatment-related deaths. There was no difference in complications among groups (p = 0.34). Treated patients without thrombosis had a median overall survival of 13.9 months versus 2.7 months for those treated with thrombosis and 5.2 months for the untreated group given best supportive care only (p = 0.01). CONCLUSIONS: SIR is safe in patients with HCC. Although SIR can be delivered with minimal morbidity, there might be no benefit for patients with VT. Continued emphasis on multimodality therapy in this population is needed to improve survival.