lusutrombopag and Liver-Neoplasms

Patients with hepatocellular carcinoma (HCC) secondary to chronic liver disease often require invasive procedures but frequently have thrombocytopenia. Lusutrombopag is an agonist of the thrombopoietin receptor that activates platelet production.. The per-protocol population included 270 patients (95 with HCC). A significantly higher proportion of patients with HCC who received lusutrombopag achieved the primary end point (68.0%) vs patients who received placebo (8.9%) (P < .0001); in patients without HCC, these proportions were 77.0% vs 21.6% (P < .0001). Lusutrombopag reduced the need for platelet transfusions, increased platelet counts for 3 weeks, and reduced the number of bleeding events in patients with and without HCC compared with placebo. Risk of thrombosis was similar to that of placebo.. Patients with and without HCC receiving lusutrombopag had a reduction in the number of platelet transfusions before invasive procedures compared with patients receiving placebo, with no increase in thrombosis or bleeding. L-PLUS 1: JapicCTI-132323; L-PLUS 2: ClinicalTrials.gov number no: NCT02389621.

Topics: Carcinoma, Hepatocellular; Cinnamates; Humans; Liver Neoplasms; Thiazoles; Thrombocytopenia

Thrombocytopenia represents an obstacle for invasive procedures in chronic liver disease (CLD) patients. We aimed to estimate the appropriate dose and evaluate the efficacy and safety of lusutrombopag for the treatment of thrombocytopenia before percutaneous liver radiofrequency ablation (RFA) for primary hepatic cancer in patients with CLD.. The proportion of patients who did not require platelet transfusion before RFA and that of responders were significantly higher (p < 0.01) in the 2-mg (80.0, 66.7%), 3-mg (81.3, 68.8%), and 4-mg groups (93.3, 80.0%) compared with the placebo group (20.0, 6.7%) and showed a dose-dependent effect. The incidence of AEs was 97.8 and 100% in the lusutrombopag (all groups) and placebo groups, respectively; no dose-related increase was observed. Four patients experienced thrombosis-related events (one each in the placebo and 2-mg groups, and two in the 4-mg group). A total of 16 (18%) adverse drug reactions occurred in the safety analysis set.. Lusutrombopag 3 mg once daily for 7 days was effective without raising concerns about excessive increases in platelet count.. The study is registered at JapicCTI-121944.

Topics: Aged; Aged, 80 and over; Carcinoma, Hepatocellular; Chronic Disease; Cinnamates; Double-Blind Method; Female; Half-Life; Humans; Japan; Liver Diseases; Liver Neoplasms; Male; Middle Aged; Platelet Count; Platelet Transfusion; Preoperative Care; Radiofrequency Ablation; Receptors, Thrombopoietin; Thiazoles; Thrombocytopenia; Thrombosis

The present study aimed to report our real-life experience of the TPO receptor agonist lusutrombopag for cirrhotic patients with low platelet counts.. We studied platelet counts in 1,760 cirrhotic patients undergoing invasive procedures at our hospital between January 2014 and December 2017. In addition, we studied 25 patients who were administered lusutrombopag before invasive procedures between June 2017 and January 2018. Effectiveness of lusutrombopag to raise platelet counts and to avoid transfusion and treatment-related adverse events were analyzed.. In 1,760 cirrhotic patients without lusutrombopag prior to invasive procedures, proportion of patients whose platelet counts <50,000/μL and needed platelet transfusions were 66% (n = 27/41) for radiofrequency ablation, 43% (n = 21/49) for transarterial chemoembolization, and 55% (n = 21/38) for endoscopic injection sclerotherapy / endoscopic variceal ligation, respectively. In 25 cirrhotic patients treated by lusutrombopag prior to the invasive procedures, platelet counts significantly increased compared with baseline (82,000 ± 26,000 vs. 41,000 ± 11,000/μL) (p < 0.01). Out of 25 patients, only 4 patients (16%) needed platelet transfusion before the invasive procedures. The proportion of patients with low platelet count and who needed platelet transfusions was significantly low in patients treated with lusutrombopag compared to those not treated with lusutrombopag (16% (4/25) vs. 54% (69/128), p = 0.001). Platelet counts after lusutrombopag treatment and prior to invasive procedures were lower in patients with a baseline platelet count ≤30,000/μL (n = 8) compared with those with a baseline platelet count >30,000/μL (n = 17) (50,000 ± 20,000 vs 86,000 ± 26,000/μL, p = 0.002). Patients with a baseline platelet count ≤30,000/μL with spleen index (calculated by multiplying the transverse diameter by the vertical diameter measured by ultrasonography) ≥40 cm2 (n = 3) had a lower response rate to lusutrombopag compared to those with spleen index <40 cm2 (n = 5) (0% vs. 100%, p = 0.02). Hemorrhagic complication was not observed. Recurrence of portal thrombosis was observed and thrombolysis therapy was required in one patient who had prior history of thrombosis.. Lusutrombopag is an effective and safe drug for thrombocytopenia in cirrhotic patients, and can reduce the frequency of platelet transfusions.

Topics: Aged; Carcinoma, Hepatocellular; Catheter Ablation; Chemoembolization, Therapeutic; Cinnamates; Esophageal and Gastric Varices; Female; Humans; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Platelet Count; Platelet Transfusion; Receptors, Thrombopoietin; Retrospective Studies; Sclerotherapy; Thiazoles; Thrombocytopenia

A 56-year-old Japanese man with liver cirrhosis (LC) due to hepatitis C virus was admitted to our hospital for radiofrequency ablation of residual tumor following lusutrombopag administration. Laboratory tests revealed thrombocytopenia and leukopenia. The patient's LC was managed, and he was classified as Child-Pugh A. After admission, lusutrombopag was administered for 7 days. The platelet count increased to over 50,000/mm

Topics: Carcinoma, Hepatocellular; Cinnamates; Hepatitis C; Humans; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Thiazoles; Thrombocytopenia

The efficacy of repeated lusutrombopag administration for thrombocytopenia in patients with chronic liver disease who undergo two or more planned invasive procedures is unknown. We herein report our findings regarding the effects of repeated lusutrombopag administration given to avoid platelet transfusion in a patient with chronic liver disease and thrombocytopenia. The platelet count showed a positive response to lusutrombopag treatment prior to the initial invasive procedure to treat a hepatoma, so platelet transfusion was not necessary. In conclusion, lusutrombopag may be a useful drug for patients with thrombocytopenia to avoid platelet transfusion in those undergoing two or more planned invasive procedures.

Topics: Carcinoma, Hepatocellular; Chronic Disease; Cinnamates; Female; Humans; Liver Diseases; Liver Neoplasms; Middle Aged; Platelet Count; Thiazoles; Thrombocytopenia