ribociclib and Chemical-and-Drug-Induced-Liver-Injury

Cyclin-dependent kinase (CDK) 4/6 inhibitors have shown a different adverse effect. In this case, persistent grade 3 hepatoxicity was observed after ribociclib. Therefore, ribociclib therapy was stopped, and then palbociclib was introduced. Transaminase levels returned to normal by switching to palbociclib therapy.. 71-year-old postmenopausal female patient with luminal subtypes of metastatic breast cancer treated with ribociclib.. Grade 3 hepatotoxicity secondary to ribociclib developed. She was successfully treated with palbociclib 125 mg.. In our case, palbociclib was started with a full dose, to increase treatment success. Starting with a 125 mg dose was not cause any toxicity. Nevertheless, laboratory follow-up is required in terms of neutropenia and increased transaminases.

Topics: Aged; Aminopyridines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemical and Drug Induced Liver Injury; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Protein Kinase Inhibitors; Purines

Hepatotoxicity is observed due to cyclin-dependent kinase (CDK4/6) inhibitors used to treat hormone receptor-positive metastatic breast cancer. However, it should not be ignored that denosumab may be hepatotoxic, although it is rare.. A 73-year-old female patient with breast cancer with axillary lymph node, adrenal gland and bone metastases was started on ribociclib letrozole and denosumab treatment. Ribociclib treatment was discontinued due to grade 4 hepatotoxicity during treatment, but liver function tests did not decrease. After discontinuation of denosumab treatment, alanine aminotransferase and aspartate aminotransferase values regressed to baseline values.. Despite the discontinuation of ribociclib treatment, other causes of liver toxicity were investigated due to persistence of hepatic transaminases and elevation. Autoimmune hepatitis markers were negative. Hepatobiliary USG did not reveal any pathological findings except hepatosteatosis. Liver biopsy was performed to determine the etiology. Pathology result was compatible with acute hepatocellular damage (in favor of toxic hepatitis). A decrease in liver values was detected after discontinuation of denosumab treatment.. Although cases with improvement in liver enzymes have been reported after discontinuation of ribociclib, no improvement in hepatotoxicity was observed in our case. Since the liver biopsy was toxic hepatitis, it was thought that other drugs used by the patient might cause this toxicity, and a significant decrease was observed in liver values after discontinuation of denosumab. Denosumab-induced liver toxicity is very rare, and there are only a limited number of cases in the literature.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemical and Drug Induced Liver Injury; Denosumab; Female; Humans; Letrozole; Receptor, ErbB-2

Topics: Aminopyridines; Breast Neoplasms; Chemical and Drug Induced Liver Injury; Female; Humans; Purines

A 59-year-old woman presented with a bone-only metastatic luminal breast cancer. She received first-line treatment with aromatase inhibitors associated with a cyclin-dependent kinase (CDK) 4/6 inhibitor, ribociclib. She developed Grade 3 elevated transaminases leading us to interrupt ribociclib permanently. Specific toxicity of the CDK 4/6 inhibitor ribociclib was retained. Once transaminase levels normalized, the patient initiated another CDK4/6 inhibitor, palbociclib, using an escalating dose without reappearance of hepatic injury. This case suggests the possibility of rechallenge after hepatic toxicity with a different CDK 4/6 inhibitor using dose escalation and careful monitoring.

Topics: Alanine Transaminase; Aminopyridines; Aromatase Inhibitors; Aspartate Aminotransferases; Bone Neoplasms; Breast Neoplasms; Carcinoma, Lobular; Chemical and Drug Induced Liver Injury; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Drug Substitution; Drug Therapy, Combination; Female; Humans; Letrozole; Middle Aged; Piperazines; Protein Kinase Inhibitors; Purines; Pyridines

CDK4/6 inhibitors in association with aromatase inhibitors have led to a paradigm shift in the management of metastatic positive hormone-receptors breast cancer. Liver toxicity is common with these agents, but no data are reported on the sequential use of these CDK4/6 inhibitors in case of confirmed efficacy and intolerable toxicity. In this article, we report the successful use of Palbociclib in a metastatic positive hormone-receptors breast cancer patient after initial response to Ribociclib, which was interrupted for grade 4 liver toxicity.

Topics: Aminopyridines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemical and Drug Induced Liver Injury; Female; Humans; Letrozole; Liver; Middle Aged; Piperazines; Protein Kinase Inhibitors; Purines; Pyridines; Receptors, Estrogen; Receptors, Progesterone; Zoledronic Acid

Cyclin-dependent kinase inhibitors (CDKIs) and endocrine therapy (ET) are the corner-stone of systemic therapy for patients with hormone-positive (HR+) HER2-negative metastatic breast cancer (MBC). However, limited data exist regarding rechallenge treatment strategies with CDKIs after limiting toxicity. In this report, we provide evidence of the safety and efficacy of sequential treatment with palbociclib or abemaciclib in 6 HR+/HER- MBC patients who experienced grade ≥3 ribociclib-induced hypertransaminasemia. Until results from large observational or randomized studies are communicated, empirical evidence may help make individualized decisions on CDKI rechallenge beyond ribociclib-induced unacceptable liver toxicity.

Topics: Aminopyridines; Antineoplastic Agents; Benzimidazoles; Breast Neoplasms; Chemical and Drug Induced Liver Injury; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Drug Substitution; Female; Humans; Middle Aged; Piperazines; Protein Kinase Inhibitors; Purines; Pyridines; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies; Transaminases; Treatment Outcome