A rare case of Takotsubo cardiomyopathy.

BACKGROUND: The recent advent of the cyclin-dependent kinase (CDK) 4/6 inhibitors has considerably evolved hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer treatment. Palbociclib, an orally administered pyridopyrimidine derivative, was the first CDK4/6 inhibitor to be introduced into daily clinical practice in combination with classic endocrine backbone, based on progression-free survival (PFS) benefit assessed in the pivotal PALOMA series of randomized clinical trials. Regarding its safety profile, neutropenia and leukopenia are the most common and well-defined adverse effects, while cardiac complications are rather scarce. CASE REPORT: We present the rare case of a middle-aged female patient with HR+/HER2- metastatic breast cancer, without prior exposure to cardiotoxic antineoplastic agents, who developed Takotsubo cardiomyopathy (TTC) in the context of systemic therapy with palbociclib plus letrozole combination. CONCLUSIONS: Pharmacovigilance and experimental studies are warranted to confirm any causative relationship and to explore the underlying pathophysiology, respectively.

Cyclin-dependent kinase (CDK) inhibitors in solid tumors: a review of clinical trials.

Cyclin-dependent kinases (CDKs) play a key regulating role in the cell cycle, which is almost universally altered in cancer, leading to sustained proliferation. Early pan-CDK inhibitors showed poor results in clinical trials for solid malignancies, as the lack of selectivity produced significant toxicity. The production of more selective inhibitors led to significant developments in cancer therapy, as CDK4/6 inhibitors in combination with endocrine therapy changed the landscape of the treatment of hormone-receptor positive (HR +) metastatic breast cancer. Recently, Trilaciclib demonstrated benefits regarding hematological toxicity compared to placebo when administered in combination with chemotherapy in small cell lung cancer. Newer agents, such as SY-5609, a selective CDK7 inhibitor, have also shown promising results in early clinical trials. In this paper, we review the data from clinical trials of CDK inhibitors in solid tumors, either as a monotherapy or in combination with other agents, with an emphasis on novel agents and potential new indications for this drug class.

Tinzaparin Safety in Patients With Cancer and Renal Impairment: A Systematic Review.

Low-molecular-weight heparins are approved for primary and secondary venous thromboembolism prevention. Tinzaparin is the low-molecular-weight heparin with the highest average molecular weight. The purpose of this systematic review is to provide an update regarding the safety profile of tinzaparin, prescribed either as a prophylactic or as a therapeutic regimen for venous thromboembolism in special populations, including cancer patients and patients with renal impairment. We identified prospective studies up to August 2020 reporting safety outcomes for cancer patients and patients with renal impairment on tinzaparin regimens. In patients with cancer major bleeding rates fluctuated between 0.8% and 7%. Patients on tinzaparin exhibited significantly lower rates of clinically relevant nonmajor bleeding events in comparison with those on vitamin K antagonists. Bioaccumulation of tinzaparin was not correlated with age, body weight or creatinine clearance. Periodic administration of either prophylactic or therapeutic doses of tinzaparin did not result in bioaccumulation, even in patients with severe renal impairment and creatinine clearance < 20 ml/min. Major bleeding rates for non-cancer patients with renal impairment on prophylactic tinzaparin regimens were 0%. Non-cancer patients with renal impairment on therapeutic tinzaparin regimens exhibited major bleeding in 0 to 3.4% of cases; major bleeding rates were higher for cancer patients with renal impairment on therapeutic tinzaparin regimens (4.3 to 10%). Tinzaparin can be used without dose adjustment in patients with severe renal impairment and creatinine clearance > 20 ml/min. Tinzaparin represents a safe choice for special populations at increased risk for thrombosis and bleeding.

Omalizumab for refractory chronic spontaneous urticaria during concurrent immunomodulatory therapy for multiple sclerosis.

SUMMARY: Data derived from previous clinical trials and real-life studies have shown that omalizumab may represent an effective third-line treatment option for patients with chronic spontaneous urticaria (CSU) refractory to standard antihistamine treatment. Nevertheless, the safety and efficacy of omalizumab treatment for CSU, when administered concurrently with other immunomodulatory agents remains largely unknown. We herein present the case of a female patient with relapsing-remitting multiple sclerosis (RRMS), under treatment with interferon beta-1a, azathioprine and gabapentin, who was successfully treated with omalizumab for refractory CSU. To the best of our knowledge, this is the first reported case attesting to the safety and efficacy of omalizumab for CSU when administered concurrently with other immunomodulatory agents.

Treating patients with ALK-rearranged non-small-cell lung cancer: mechanisms of resistance and strategies to overcome it

Anaplastic lymphoma kinase (ALK) rearrangement is detected in 3-7% of patients with non-small-cell lung cancer. Crizotinib is an ALK inhibitor, which was approved in 2011 for the treatment of ALK-positive lung cancer. Despite the initial enthusiasm, most of the patients develop resistance within the first year of treatment. The main mechanisms are secondary mutations and bypass track activation. Moreover, crizotinib has low penetration into the central nervous system. The need to overcome these limitations has led to the development of second-generation inhibitors that have better effectiveness against crizotinib-resistant mutations and brain metastases. Ceritinib and alectinib are the only approved drugs of this group. Many ongoing trials try to define the most appropriate agent for the treatment of ALK-positive lung cancer depending on the responsible mechanism. This review focuses on the current data regarding the potential mechanisms of resistance to ALK inhibitors and the strategies to overcome it (AU)

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Treating patients with ALK-rearranged non-small-cell lung cancer: mechanisms of resistance and strategies to overcome it.

Anaplastic lymphoma kinase (ALK) rearrangement is detected in 3-7% of patients with non-small-cell lung cancer. Crizotinib is an ALK inhibitor, which was approved in 2011 for the treatment of ALK-positive lung cancer. Despite the initial enthusiasm, most of the patients develop resistance within the first year of treatment. The main mechanisms are secondary mutations and bypass track activation. Moreover, crizotinib has low penetration into the central nervous system. The need to overcome these limitations has led to the development of second-generation inhibitors that have better effectiveness against crizotinib-resistant mutations and brain metastases. Ceritinib and alectinib are the only approved drugs of this group. Many ongoing trials try to define the most appropriate agent for the treatment of ALK-positive lung cancer depending on the responsible mechanism. This review focuses on the current data regarding the potential mechanisms of resistance to ALK inhibitors and the strategies to overcome it.

Changes of acute-phase protein levels in the serum of lung cancer patients following radiotherapy.

PURPOSE: the assessment of serum level changes of C-reactive protein (CRP), ferritin (FER), and albumin (ALB) as inflammation markers in Non Small Cell Lung Cancer patients (stages IIIA - inoperable and stage IIIB) treated with radiotherapy. Significant findings: Normal pre-radiotherapy levels of CRP were found in 18 patients, of FER in 17, and of ALB in 22. Higher levels of CRP were found in 9 patients and of FER in 10. Lower ALB was found in 5 patients.Post-radiotherapy CRP levels were significantly higher (compared to the pre-radiotherapy levels) in 25 patients. The same was observed regarding FER in 18 patients whereas 12 patients had lower post-radiotherapy levels. The statistical analysis (non parametrical Wilcoxon test) revealed that these differences were statistically significant (p-value< 0.001). CONCLUSIONS: The levels of CRP, FER, and ALB are reliable and useful biomarkers correlated with the acute complication of lung parenchyma damage induced by radiotherapy.