Use of ramucirumab for various treatment lines in real-world practice of patients with advanced hepatocellular carcinoma.

PURPOSE: Ramucirumab was shown to be effective as a second-line treatment after sorafenib in patients with advanced hepatocellular carcinoma (HCC) with alpha-fetoprotein levels > 400 ng/mL in a worldwide phase 3 trial. Ramucirumab is used in patients pretreated with various systemic therapies in clinical practice. We retrospectively examined the treatment outcomes of ramucirumab administered to advanced HCC patients after diverse systemic therapies. METHODS: Data were collected from patients with advanced HCC who received ramucirumab at three institutions in Japan. Radiological assessments were determined according to both Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 and modified RECIST and the Common Terminology Criteria for Adverse Events version 5.0 was used to assess adverse events. RESULTS: A total of 37 patients treated with ramucirumab between June 2019 and March 2021 were included in the study. Ramucirumab was administered as second, third, fourth, and fifth-line treatment in 13 (35.1%), 14 (37.8%), eight (21.6%), and two (5.4%) patients, respectively. Most patients (29.7%) who received ramucirumab as a second-line therapy were pretreated with lenvatinib. We found grade 3 or higher adverse events only in seven patients and no significant changes in the albumin-bilirubin score during ramucirumab treatment in the present cohort. The median progression-free survival of patients treated with ramucirumab was 2.7 months (95% confidence interval, 1.6-7.3). CONCLUSION: Although ramucirumab is used for various lines of treatment other than second-line immediately after sorafenib, its safety and effectiveness were not significantly different from the findings of the REACH-2 trial.

Successful treatment of chylous ascites by superselective embolization of the inflowing lymphatic vessels using a steerable microcatheter: a case study.

Background: Chylous ascites resulting from postoperative lymphatic leaks are uncommon but difficult to treat in cases with unsuccessful conservative treatment. Case report: We report the case of an 80-year-old woman who had previously undergone multiple procedures for peritoneal dissemination 3.5 months after a laparoscopic bilateral salpingo-oophorectomy for ovarian cancer. After hospital discharge, she gradually gained weight, and examination findings indicated lymphatic leakage. We performed drainage using an 8.5-French Dawson-Mueller catheter, but more aggressive treatment was deemed necessary. We determined that it would be difficult to fill the large space, in which the leaking lymph fluid was accumulating, with embolic materials. Therefore, we performed superselective embolization of these inflowing lymphatic vessels to allow control of the chylous ascites. To overcome the technical difficulty associated with the insertion of a microcatheter from a large leakage cavity into a small inflow lymphatic vessel, we adopted a triple coaxial system that utilizes a steerable microcatheter. Successful embolization resulted in marked decrease in drainage. Follow-up computed tomography revealed no evidence of reaccumulation of chylous ascites. A three-month follow-up revealed no recurrence of lymphatic leakage. Conclusions: To our knowledge, this is the first report on the treatment of large retropenitoneal chylous leakage by superselective embolization of the inflowing lymphatic vessels using steerable microcatheters. This method allows large lymphatic leaks to be treated with only a small amount of N-butyl 2-cyanoacrylate mixture and without the use of coils, and we firmly believe that it should be considered for the treatment of large refractory chylous ascites.

Sequential therapy with sorafenib and regorafenib for advanced hepatocellular carcinoma: a multicenter retrospective study in Japan.

Background Conversion from sorafenib to regorafenib is primarily an evidence-based treatment strategy in patients with advanced hepatocellular carcinoma (HCC). This study aimed to assess the safety and efficacy of sequential therapy with sorafenib and regorafenib in patients with advanced HCC by analysis of outcomes in clinical practice with the aim to complement phase III findings. Methods The medical records of patients with advanced HCC receiving regorafenib were retrieved to collect data on sorafenib administration at seven Japanese institutions. Radiological responses and adverse events were evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1 and the Common Terminology Criteria for Adverse Events version 4.0, respectively. Results Before March 2018, 44 patients were administered regorafenib for advanced HCC. The median sorafenib treatment duration was 8.4 months. The most common adverse events were similar to those reported by the RESORCE trial. The median overall survival (OS) was 17.3 months (95% confidence interval [CI] 11.4-22.9), and 17 of 37 patients (45.9%) discontinued regorafenib and received sequential systemic therapy after regorafenib. These patients had significantly longer OS than those who were treated by the best supportive care or sub-optimal therapy (not reached versus 8.7 months [95% CI 5.8-11.7]; P < 0.001). Conclusion The results based on Japanese clinical practices verified the tolerability of regorafenib in advanced HCC. Major regorafenib-associated adverse events were similar to those related to sorafenib. OS was significantly longer than expected, which might be associated with the sequential systemic therapies after regorafenib, mainly lenvatinib.

Characteristics of patients with sorafenib-treated advanced hepatocellular carcinoma eligible for second-line treatment.

Background Regorafenib has been investigated for its efficacy and safety as a second-line treatment in patients with advanced hepatocellular carcinoma (HCC). We assessed the characteristics of patients with HCC treated with sorafenib who might be eligible for second-line treatment in general and regorafenib in particular. Methods Patients with HCC treated with sorafenib were retrospectively analyzed. We defined second-line candidate patients as maintaining Child-Pugh A and ECOG-PS ≤1 at the time of sorafenib failure. We also defined regorafenib candidate patients as follows: 1) continuing sorafenib at the time of radiological progression, 2) maintaining Child-Pugh A and ECOG-PS ≤ 1 at the time of sorafenib failure, and 3) continuing sorafenib 400 mg or more without intolerable adverse events at least 20 days of the last 28 days of treatment. Results Of 185 patients, 130 (70%) and 69 (37%) were candidates for second-line treatment and regorafenib. Child-Pugh score 6 and ECOG-PS 1 at the time of starting sorafenib were significantly lower in both second-line treatment and regorafenib candidate patients. Moreover, hand-foot skin reaction and liver failure during sorafenib treatment were associated with significantly low and high probabilities, respectively, of both Child-Pugh score > 6 and ECOG-PS > 1 at the time of sorafenib failure. Conclusion Regorafenib candidate patients after sorafenib failure are limited, and generally fewer than those who are candidates for second-line treatment. A lower Child-Pugh score and a better ECOG-PS were predictors of eligibility for second-line therapy and regorafenib treatment in sorafenib-treated patients with advanced HCC patients.

Analysis of Sorafenib Outcome: Focusing on the Clinical Course in Patients with Hepatocellular Carcinoma.

BACKGROUND: Treatment outcomes of sorafenib therapy may greatly vary depending not only on tumor spread but also on past clinical processes prior to sorafenib therapy and timing of sorafenib administration in the past clinical course of hepatocellular carcinoma (HCC). We evaluated the efficacy of sorafenib in patients with HCC, taking into account of their past clinical courses. METHODS: Patients with HCC treated with sorafenib as a first-line systemic therapy, whose courses documented from the time of the initial diagnosis, were retrospectively analyzed. RESULTS: Of the 123 patients receiving sorafenib therapy at an advanced-stage, baseline characteristics differed including the rate of hepatitis C virus, Child-Pugh class, and status of intrahepatic lesions according to stage progression processes. Overall survival (OS) in patients progressed directly from the early-stage (15.3 months) was significantly longer than that in patients diagnosed at the advanced-stage (5.3 months, P = 0.022) and progressed from the intermediate-stages (6.0 months, P = 0.041). Of 105 patients diagnosed at the intermediate-stage on past clinical courses, OS of starting sorafenib therapy before progression to the advanced-stage (67 patients) was significantly longer than for patients starting sorafenib therapy only after progression to the advanced-stage (38 patients) (P = 0.015). CONCLUSION: Characteristic differences between past stage progression processes might affect prognosis in advanced-stage HCC patients receiving sorafenib. Switching to sorafenib therapy before progression to the advanced-stage appears more effective than that after progression to the advanced-stage in patients diagnosed in the intermediate-stage on past clinical courses prior to sorafenib administration.

Short-term therapeutic effects of transcatheter arterial chemoembolization using miriplatin-lipiodol suspension for hepatocellular carcinoma.

PURPOSE: To retrospectively investigate the short-term therapeutic effects and adverse effects associated with the use of miriplatin-lipiodol suspension for transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC), using TACE with cisplatin-lipiodol suspension as the historical control. MATERIALS AND METHODS: The study was conducted on 48 and 50 consecutive patients with HCC who underwent TACE with miriplatin-lipiodol suspension and cisplatin-lipiodol suspension, respectively. Therapeutic effect was evaluated by mRECIST. Adverse effects were graded by CTCAE, version 4.0. The therapeutic and adverse effects were compared using Fisher's exact test and multivariate logistic regression. RESULTS: Complete remission, partial response, stable disease and progressive disease were observed in 37.5, 18.8, 33.3 and 10.4 % of patients in the miriplatin group, with the corresponding percentages being 54.0, 32.0, 14.0 and 0.0 %, respectively, in the cisplatin group. The short-term therapeutic effects were statistically significantly worse in the miriplatin group than in the cisplatin group, even after adjustment for tumor size and Child-Pugh class. The rates of nausea and serum creatinine elevation were statistically significantly lower in the miriplatin group (p < 0.05). CONCLUSION: TACE using miriplatin-lipiodol suspension yielded worse short-term responses than cisplatin-lipiodol suspension; however, the rates of adverse events were significantly lower in the miriplatin group.