scholarly journals Initial experience with the combination of atezolizumab and bevacizumab in patients with unresectable hepatocellular carcinoma progressing after tyrosine kinase inhibitor therapy: A multicenter prospective observational study

2021 ◽  
Author(s):  
Rie Sugimoto ◽  
Takeaki Satoh ◽  
Akihiro Ueda ◽  
Takeshi Senju ◽  
Yuki Tanaka ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Side Effects ◽  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Response To Treatment ◽  
Therapeutic Effects ◽  
Unresectable Hepatocellular Carcinoma ◽  
Study Results ◽  
Previously Treated

Abstract Background There is no evidence for the efficacy of atezolizumab plus bevacizumab treatment in patients with hepatocellular carcinoma previously treated with tyrosine kinase inhibitors (TKIs). Methods Twelve patients treated with atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma (HCC) and previously treated with TKIs were enrolled in the study. Results The treatment lines ranged from second line to sixth line. HCC staging was Barcelona Clinic Liver Cancer (BCLC) stage B in four cases and BCLC stage C in eight cases. The overall response rate and disease control rate according to the response evaluation criteria in solid tumors (RECIST) were 18.1% and 54.4%, respectively. Progression-free survival was 2.7 months, indicating that early response to treatment may differ depending on the type of previous therapy. The side effects profile also differed from that observed in IMbrave150, a phase 3 trial of atezolizumab plus bevacizumab, with many adverse events related to liver reserve. Conclusions The therapeutic effects and side effects differed from those previously reported during the treatment course of atezolizumab plus bevacizumab as first-line therapy.

scholarly journals Nilotinib therapy in an imatinib intolerant chronic myeloid leukemia patient with pulmonary severe hypertension

2015 ◽  
Vol 4 (2S) ◽  
pp. 17-20
Author(s):  
Mario Annunziata
Keyword(s):  
Side Effects ◽  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Chronic Myeloid Leukemia Patient ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
Molecular Response ◽  
Cutaneous Rash

Imatinib mesylate is a tyrosine kinase inhibitor that has significant efficacy in the treatment of chronic myelogenous leukemia. In general, hematologic and extrahematologic side effects of imatinib therapy are mild to moderate, with the large majority of patients tolerating prolonged periods of therapy. However, a minority of patients are completely intolerant of therapy, while others are able to remain on therapy despite significant side effects. Here, we describe a chronic phase CML patient with pulmonary arterial hypertension, mechanical hearth valve, who experienced extrahematologic adverse event (persistent grade III cutaneous rash, despite two discontinuations of imatinib and using of steroid). Necessitating switch to one of new tyrosine kinase inhibitors, nilotinib, has resulted in complete cytogenetic response and major molecular response, after 3 and 6 months, respectively. No cross-intolerance with imatinib was observed during nilotinib therapy. Besides, this clinical case suggests that warfarin and nilotinib can be used concurrently without the risk of increased anticoagulant effect.

Phase IIa safety and efficacy of milciclib, a pan-cyclin dependent kinase inhibitor, in unresectable, sorafenib-refractory or -intolerant hepatocellular carcinoma patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16711-e16711
Author(s):  
Erica Villa ◽  
Fabio Piscaglia ◽  
Rabit Geva ◽  
George Dalecos ◽  
George Papatheodoridis ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Checkpoint Inhibitors ◽  
Primary Objective ◽  
Response To Treatment ◽  
Cyclin Dependent Kinase ◽  
Advanced Hcc ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Secondary Endpoints

e16711 Background: Current hepatocellular carcinoma (HCC) therapeutics, tyrosine kinase inhibitors (TKI) and checkpoint inhibitors (CI), provide limited improvement in overall survival, suggesting the need to identify drugs with broad-spectrum mechanisms of action, used alone or in combination with a TKI or CI. Milciclib, a pan cyclin dependent kinase inhibitor, exhibited anti-cancer activity in refractory solid malignancy patients. The primary objective of this trial was to evaluate safety and tolerability of milciclib in sorafenib-refractory or intolerant advanced HCC patients. Methods: Single arm and multi-center study in advanced HCC patients was conducted in Italy, Greece and Israel. Milciclib was administered orally for up to 6 cycles. Each cycle consisted of 100mg milciclib daily for 4d on/3d off/week for 4 weeks. Safety assessment was the primary endpoint and secondary endpoints included progression free survival (PFS), time to progression (TTP) and clinical benefit rate (CBR). Results: A total of 31 patients were enrolled and 28 were evaluable for efficacy, of which 14 (50%) completed 6-months of treatment. Milciclib was well-tolerated with manageable toxicities. Eighteen of 31 treated patients had drug-related adverse events (AEs) with most frequent (≥5%) occurrence of drug-related diarrhea, nausea, asthenia, fatigue, retinal hemorrhage, rash and myalgia. No drug-related deaths were recorded. Nine of 14 patients (64%) continued treatment under Compassionate Use after study completion. Seven patients received milciclib until 9, 9, 10, 11, 13, 13 and 16 months. The remaining 2 patients are in the 16th month of treatment. Clinical response to treatment, assessed by mRECIST (independent radiological review), is shown in the Table. Both median TTP and PFS were 5.9 months. Conclusions: Milciclib, acting via a new mechanism, was safe, well-tolerated and met primary and secondary endpoints with 61% CBR. These promising clinical data warrant further evaluation of milciclib. Clinical trial information: NCT03109886 . [Table: see text]

scholarly journals Efficacy of the immune checkpoint inhibitor nivolumab in the treatment of advanced hepatocellular carcinoma with the exhausted possibilities of therapy with tyrosine kinase inhibitors

2021 ◽  
pp. 84-93
Author(s):  
A. Yu. Goryainova ◽  
A. I. Stukan ◽  
R. A. Murashko ◽  
S. V. Sharov ◽  
O. I. Kirsanova ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Side Effects ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Multiple Drug Resistance ◽  
Response To Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Surgical Methods ◽  
A Priority

Hepatocellular carcinoma is one of the most formidable and deadly cancers. The limited possibilities of surgical methods of treatment as well as the formation of multiple drug resistance caused by the biological characteristics of both the liver tissue itself and tumor cells with their microenvironment determine the unsatisfactory indicators of relapse free survival and overall survival of patients. In addition, therapy with tyrosine kinase inhibitors, which has become the “gold” standard, has limited possibilities: a large number of side effects significantly reduce the quality of life and adherence to treatment in patients with hepatocellular cancer. The search for molecular biological targets, as well as new therapeutic agents that block these targets, does not always lead to positive results. Immunotherapy in this sense is a priority, having good tolerance, a low number of side effects, no need for additional testing of the patient’s biological material before starting treatment, high efficiency and a long response time. However, there are many unresolved questions about the duration of therapy, predicting its efficacy, the optimal combination of drugs or the use of monotherapy, the formation of priority subgroups of patients. Understanding the mechanisms of immune evasion, an ability that hepatocellular carcinoma possesses, – is the key to successful use of immunotherapeutic agents alone, in combination with tyrosine kinase inhibitors, antiangiogenic drugs or among themselves. This article provides an overview of data from clinical studies of modern drugs for the treatment of hepatocellular carcinoma and describes the mechanism of liver immunological tolerance as a possible predictive marker of sensitivity to immunotherapy. It seems promising to study the role of cells in the microenvironment of hepatocellular carcinoma for predicting the effectiveness of immunotherapy. The clinical example is used to demonstrate the successful experience of using the immunotherapeutic drug nivolumab in the treatment of hepatocellular carcinoma resistance to tyrosine kinase inhibitors. This is a classic example of duration of response to therapy, lack of reactivation of chronic viral hepatitis and controlled toxicity. All these indicators enable the clinician to consider immunotherapy as a priority option for the treatment of inoperable hepatocellular carcinoma. 

EGFR mutation analysis and treatment outcomes with tyrosine kinase inhibitors in EGFR mutants: The Manchester Lung Cancer Group Experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18095-e18095
Author(s):  
Rahul Peck ◽  
Elizabeth Connolly ◽  
Paul Taylor ◽  
Corinne Faivre-Finn ◽  
Fiona Hellen Blackhall ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Response To Treatment ◽  
Smoking History ◽  
Egfr Mutations ◽  
Published Data ◽  
Duration Of Treatment

e18095 Background: The presence of Epidermal Growth Factor Receptor (EGFR) activating mutations in patients with NSCLC was first described in 2005. Tumours exhibiting these mutations show sensitivity to treatment with an oral Tyrosine Kinase Inhibitor. Testing for EGFR mutations in patients with non-squamous NSCLC began in the Greater Manchester and Cheshire network in the last quarter of 2009. Methods: We audited the notes of consecutive patients who were identified with an activating EGFR mutation by the Central Manchester Genetics Laboratory between November 2009 and October 2011. Results: A total of 110 mutations were identified in tumour tissue from 98 patients. 13.6% were in exon 18, 38.2% in exon 19, 15.4% in exon 20 and 32.8% in exon 21. 65% of patients were female. The median age was 69 years (36-89). Notes were available for 85 patients, 59 of whom received treatment with an EGFR TKi. 7 had previously received radical treatment and 19 never received treatment. 7% were current smokers, 40% were ex-smokers, 30.6% had never smoked and smoking history was not documented in 22.4%. An initial response to treatment was seen in 55%, with stable disease in 15%.The mean duration of treatment was 7.6 months (2 weeks – 23 months), with 24 patients still receiving a TKi at the time of data analysis. The most commonly seen toxicities were diarrhoea and rash. Only 1 patient had no documented toxicity from their TKi. 17 patients (29%) had treatment discontinued or interrupted because of toxicity. In 8 of these, treatment was re-introduced at a reduced dose, and 3 patients went back to full dose. Conclusions: Our results confirm that treatment with a TKi is effective for those patients whose tumours harbour EGFR mutations, with a side effect profile consistent with published data.

Tyrosine kinase inhibitors for unresectable hepatocellular carcinoma in adults

2021 ◽  
Vol 2021 (11) ◽  
Author(s):  
Winson Cheung ◽  
Yuan Xu ◽  
Shiying Kong ◽  
Roberta Elisa Rossi ◽  
Paolo Baldo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Unresectable Hepatocellular Carcinoma

A modified perfusion protocol for pulmonary endarterectomy in a patient with a hematologic malignancy treated with a tyrosine kinase inhibitor

Perfusion ◽  
2021 ◽  
pp. 026765912110521
Author(s):  
Renard G Haumann ◽  
Dedré Buys ◽  
Eline Hofland ◽  
Hans WA Romijn ◽  
Suzanne K Kamminga ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Side Effects ◽  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Hematologic Malignancy ◽  
Circulatory Arrest ◽  
Myelogenous Leukemia ◽  
Pulmonary Endarterectomy ◽  
Simple Modification

Tyrosine kinase inhibitors (TKI) are known to be highly effective in the treatment of various cancers with kinase-domain mutations such as chronic myelogenous leukemia. However, they have important side effects such as increased vascular permeability and pulmonary hypertension. In patients undergoing pulmonary endarterectomy with deep hypothermic circulatory arrest, these side effects may exacerbate postoperative complications such as reperfusion edema and persistent pulmonary hypertension. We report on a simple modification of the perfusion strategy to increase intravascular oncotic pressure by retrograde autologous priming and the addition of packed cells and albumin in a patient treated with a TKI.

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