The prevalence of PE and mortality due to PE is high in cancer patients. Risk stratification for venous thromboembolism (VTE) should be done in all cancer patients and thromboprophylaxis should be optimally used.
Background This phase I dose de-escalation study aimed to assess the tolerability, safety, pharmacokinetics (PK), and efficacy of sequentially decreasing doses of sorafenib in combination (SAM) with atorvastatin (A, 10 mg) and metformin (M, 500 mg BD) in patients with advanced hepatocellular carcinoma (HCC). Methods Patients were enrolled in 1 of 4 sequential cohorts (10 patients each) of sorafenib doses (800 mg, 600 mg. 400 mg, and 200 mg) with A and M. Progression from one level to the next was based on prespecified minimum disease stabilization (at least 4/10) and upper limits of specific grade 3-5 treatment-related adverse events (TRAE). Results The study was able to progress through all 4 dosing levels of sorafenib by the accrual of 40 patients. Thirty-eight (95%) patients had either main portal vein thrombosis or/and extra-hepatic disease. The most common grade 3-5 TRAEs were hand-foot-syndrome (grade 2 and grade 3) in 3 (8%) and transaminitis in 2 (5%) patients, respectively. The plasma concentrations of sorafenib peaked at 600 mg dose, and the concentration threshold of 2400 ng/mL was associated with higher odds of achieving time to exposure (TTE) concentrations >75% centile (odds ratio [OR] = 10.0 [1.67-44.93]; P = .01). The median overall survival for patients without early hepatic decompensation (n = 31) was 8.9 months (95% confidence interval [CI]: 3.2-14.5 months). Conclusion The SAM combination in HCC patients with predominantly unfavorable baseline disease characteristics showed a marked reduction in sorafenib-related side effects. Studies using sorafenib 600 mg per day in this combination along with sorafenib drug level monitoring can be evaluated in further trials. (Trial ID: CTRI/2018/07/014865).
Cisplatin has been used for over 40 years in various cancer chemotherapies. Toxicity induced by cisplatin-based therapeutic regimens include gastrointestinal toxicity, myelotoxicity, neurotoxicity, ototoxicity and nephrotoxicity. Cisplatin-based regimens have been associated with a wide range of cardiovascular complications. In this paper, we report 2 cases of cisplatin-induced cardiotoxicity.We present cases of 2 young patients who developed acute myocardial infarction during combination chemotherapy with bleomycin, etoposide and cisplatin. The first patient had acute anterior wall ST elevation myocardial infarction and the second one had acute myocardial infarction with peripheral arterial thromboembolism.Cisplatin use can result in cardiovascular events. Clinicians should be very cautious while managing patients on cisplatin-based chemotherapy. Early recognition of cardiotoxicity will allow for timely prevention of permanent cardiac damage.
Atrial fibrillation is a well recognized side effects of several drugs. However it is ignored since most studies have failed to show that it impacts survival adversely. This is not the case with ibrutinib, especially amongst patients with pre-existing cardiac morbidities. In this article, we provide practical consensus guidelines for cancer patients being commenced on therapy with ibrutinib.
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