Phase 2 trial comparing sorafenib, pravastatin, their combination or supportive care in HCC with Child–Pugh B cirrhosis

Blanc, Jean‐Frédéric; Khemissa, Faïza; Bronowicki, Jean–Pierre; Montérymard, Carole; Perarnau, Jean–Marc; Bourgeois, Vincent; Obled, Stéphane; Abdelghani, Méher Ben; Mabile-Archambeaud, Isabelle; Faroux, Roger; Seitz, Jean‐François; Locher, Christophe; Senellart, Hélène; Villing, Anne-Laure; Audemar, Franck; Costentin, Charlotte; Deplanque, Gaël; Manfrédi, Sylvain; Edeline, Julien

doi:10.1007/s12072-020-10120-3

Cited by 35 publications

(27 citation statements)

References 28 publications

(33 reference statements)

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“…Thus, in patients with BCLC B and C, data suggest a prolonged survival for DSM-TACE compared to best supportive care. Regarding Child-Pugh class, patients with Child-Pugh B receiving placebo/best supportive care instead of systemic treatment had a reported median OS within the range of 3.5-8.0 months, which was substantially lower than the achieved survival of 15.2 months when treated with DSM-TACE, thus suggesting a survival benefit [23][24][25].…”

Section: Discussionmentioning

confidence: 94%

European Multicenter Study on Degradable Starch Microsphere TACE: The Digestible Way to Conquer HCC in Patients with High Tumor Burden

Ludwig

Iezzi

Theysohn

et al. 2021

Cancers

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To evaluate the safety and efficacy of transarterial chemoembolization with degradable starch microspheres (DSM-TACE) for the treatment of hepatocellular carcinoma (HCC) with a high tumor burden ineligible for or failing other palliative therapies, 121 patients from three European centers were included. Kaplan–Meier analysis was used for median overall survival (OS) and time to progression (TTP, mRECIST criteria) in months with a 95% confidence interval (95% CI). Uni- (UVA) and multivariate (MVA) analyses were performed using the Cox Proportional Hazard Model. The median OS of the study cohort was 15.5 (13.3–18.7) months. The UVA identified HCC lesions ≤10 cm, unilobar involvement, lower Child–Pugh class and Barcelona Clinic Liver Cancer (BCLC) stage, absence of vascular invasion, and extrahepatic metastases as factors for prolonged survival. MVA confirmed lesions of ≤10 cm and unilobar disease as independent OS factors. Median TTP was 9.5 (7.6–10.3) months. The best response was achieved after a median of 3 (range: 1–6) treatments with CR/PR/SD/PD in 13.5%/44.5%/25.2%/16.8%, respectively. DSM-TACE was well tolerated with no major clinical adverse events and only limited major laboratory events. Preserved liver function was observed after repetitive DSM-TACE treatments. Repetitive DSM-TACE is a safe, well-tolerated and effective treatment option for HCC patients with high tumor burden ineligible or failing other palliative therapies.

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Section: Discussionmentioning

confidence: 94%

European Multicenter Study on Degradable Starch Microsphere TACE: The Digestible Way to Conquer HCC in Patients with High Tumor Burden

Ludwig

Iezzi

Theysohn

et al. 2021

Cancers

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“…Finally, McNamara et al [23] published a metanalysis of studies including HCC patients (both Child-Pugh A and B) treated with sorafenib. The results regarding 1684 Child-Pugh B patients are similar to those of the above-mentioned studies, with a worse prognosis than Child-Pugh A patients, due to their poorer liver function, but no conclusions on the efficacy of sorafenib might be drawn in these patients.…”

Section: Discussionmentioning

confidence: 99%

BOOST: a phase 3 trial of sorafenib vs. best supportive care in first line treatment of hepatocellular carcinoma in patients with deteriorated liver function

Daniele¹,

Schettino²,

Arenare³

et al. 2021

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Aim: Only patients with good liver function {[Child-Pugh (CP)] A class} were eligible for trials testing sorafenib as first-line treatment of hepatocellular carcinoma (HCC); nevertheless, the drug was authorized without restrictions based on liver function. Therefore, we planned to test sorafenib efficacy and safety in patients with HCC and deteriorated liver function (CP-B). Methods:This was an open-label, multicenter, randomized phase 3 trial. Patients with HCC, no previous systemic therapy, and CP-B score 7-9 were assigned 1:1 to best supportive care alone (control arm) or with standard dose sorafenib (experimental arm). Overall survival (OS) was the primary endpoint. To detect a 0.70 HR of death, with 80% power, and two-tailed α error 0.05, 234 events were required. The study closed prematurely because of slow accrual. Descriptive analyses are reported.Results: From 2012 to 2017, 13 Italian centers randomized 35 patients. In total, 28 deaths were recorded, 12 without and 16 with sorafenib; median OS was 4.9 (95%CI: 1.2-5.6) and 3.5 months (95%CI: 1.3-5.3), respectively. At least one severe adverse event was reported in 2/15 (13.3%) without and 9/17 (52.9%) patients with sorafenib.Conclusions: This trial failed its planned enrolment goal, showing the difficulty in performing clinical trials with drugs already registered with a label broader than what available evidence supports.

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“…There are several phase II or III RCTs that studied this effect. Sorafenib plus pravastatin did not improve time to progression (TTP), PFS, and OS compared with sorafenib alone [131,132], but improved TTP in another study [133]. In a study of transcatheter arterial embolization followed by fluorouracil, the addition of pravastatin prolonged OS compared with the standard therapy alone in advanced hepatocellular carcinoma [134].…”

Section: Hepatocellular Carcinomamentioning

confidence: 99%

Beyond Lipid-Lowering: Effects of Statins on Cardiovascular and Cerebrovascular Diseases and Cancer

et al. 2022

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The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, are administered as first-line therapy for hypercholesterolemia, both as primary and secondary prevention. Besides the lipid-lowering effect, statins have been suggested to inhibit the development of cardiovascular disease through anti-inflammatory, antioxidant, vascular endothelial function-improving, plaque-stabilizing, and platelet aggregation-inhibiting effects. The preventive effect of statins on atherothrombotic stroke has been well established, but statins can influence other cerebrovascular diseases. This suggests that statins have many neuroprotective effects in addition to lowering cholesterol. Furthermore, research suggests that statins cause pro-apoptotic, growth-inhibitory, and pro-differentiation effects in various malignancies. Preclinical and clinical evidence suggests that statins inhibit tumor growth and induce apoptosis in specific cancer cell types. The pleiotropic effects of statins on cardiovascular and cerebrovascular diseases have been well established; however, the effects of statins on cancer patients have not been fully elucidated and are still controversial. This review discusses the recent evidence on the effects of statins on cardiovascular and cerebrovascular diseases and cancer. Additionally, this study describes the pharmacological action of statins, focusing on the aspect of ‘beyond lipid-lowering’.

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Phase 2 trial comparing sorafenib, pravastatin, their combination or supportive care in HCC with Child–Pugh B cirrhosis

Cited by 35 publications

References 28 publications

European Multicenter Study on Degradable Starch Microsphere TACE: The Digestible Way to Conquer HCC in Patients with High Tumor Burden

European Multicenter Study on Degradable Starch Microsphere TACE: The Digestible Way to Conquer HCC in Patients with High Tumor Burden

BOOST: a phase 3 trial of sorafenib vs. best supportive care in first line treatment of hepatocellular carcinoma in patients with deteriorated liver function

Beyond Lipid-Lowering: Effects of Statins on Cardiovascular and Cerebrovascular Diseases and Cancer

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