ABSTRACT

Thrombocytopenia occurs frequently in patients with cancer-associated thrombosis (CAT), however prospective evaluation of clinical outcomes following randomization to anticoagulants is limited. The HOKUSAI VTE Cancer study was a randomized, open-label, non-inferiority, phase III trial comparing dalteparin with edoxaban in CAT patients. This post hoc analysis of Hokusai VTE Cancer Study was performed to compare outcomes in patients with platelet count ≤100 K/μL at one or more specified time points (baseline, 1-month, or 3-month) versus those without thrombocytopenia. Cumulative incidences at 180 days were calculated with death as a competing risk. The primary outcome was major bleeding; secondary outcomes were clinically relevant non-major bleeding (CRNMB), recurrent thrombosis, and survival. The analysis included 1,045 patients with primarily solid tumor malignancies (89%), median age 65 years, and 52% male. The thrombocytopenia group comprised 9.6% (N=101) of the cohort and relative to the non-thrombocytopenia cohort (N=944), experienced significantly higher major bleeding (9.0% vs. 4.0%, sub-distribution hazard ratio (SHR) 2.4, P=0.02) and CRNMB (17.9% vs. 9.6%, SHR 2.0, P=0.01). Thrombocytopenia did not impact recurrent VTE (9.8% vs. 7.4%, SHR 1.3, P=0.37) nor overall mortality (21.8% vs. 26.0%, HR 0.9, P=0.48). Major bleeding was higher in patients with thrombocytopenia and gastrointestinal malignancies receiving edoxaban versus dalteparin (16.8% vs 0, p.

PMID:37855029 | DOI:10.3324/haematol.2023.284192

07:10

PubMed articles on: Cancer & VTE/PE

In vivo evaluation of the pharmacokinetic interactions between almonertinib and rivaroxaban, almonertinib and apixaban

Front Pharmacol. 2023 Oct 4;14:1263975. doi: 10.3389/fphar.2023.1263975. eCollection 2023.

ABSTRACT

Background: Almonertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is commonly used as a first-line treatment for non-small cell lung cancer (NSCLC) patients with EGFR T790M mutations. Rivaroxaban and apixaban are a selective, direct factor Xa inhibitor used to treat venous thromboembolism (VTE), which is a frequent complication of NSCLC. Rivaroxaban and apixaban are substrates of CYP3A4, P-gp and BCRP, whereas almonertinib is an inhibitor of P-gp and BCRP. Rivaroxaban or apixaban are often prescribed together with almonertinib in NSCLC patients, but clear information on pharmacokinetic drug interaction is lacking. Therefore, this study aimed to unravel the extent of interactions between almonertinib-rivaroxaban and almonertinib apixaban in rats, and whether the pharmacokinetic interaction can be mitigated by rivaroxaban and apixaban dose adjustment. Methods: Rats were divided into ten groups (n = 6) that received rivaroxaban (2 mg/kg) (group 1), apixaban (0.5 mg/kg) (group 2), almonertinib (15 mg/kg) (group 3, group 4), almonertinib with rivaroxaban (2 mg/kg) (group 5), almonertinib with rivaroxaban (1 mg/kg) (group 6), almonertinib with apixaban (0.5 mg/kg) (group 7), almonertinib with apixaban (0.25 mg/kg) (group 8), rivaroxaban (2 mg/kg) with almonertinib (group 9), apixaban (0.5 mg/kg) with almonertinib (group 10). The concentrations of drugs were determined by an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The levels of messenger RNA were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Results and Discussion: The results indicate that almonertinib increased the Cmax and AUC0-t of 2 mg/kg rivaroxaban by 3.30 and 3.60-fold, 1 mg/kg rivaroxaban by 1.28 and 1.90-fold. Almonertinib increased the Cmax and AUC0-t of 0.5 mg/kg apixaban by 2.69 and 2.87-fold, 0.25 mg/kg apixaban by 2.19 and 2.06-fold. In addition, rivaroxaban also increased systemic exposure to almonertinib. The results of qRT-PCR showed that almonertinib reduced the expression of Cyp3a1 in liver and intestine, and Abcb1a, Abcg2 in intestine and kidney. The pharmacokinetic results suggest that it is important to take special care of the interactions of these drugs in clinical applications.

PMID:37860116 | PMC:PMC10582335 | DOI:10.3389/fphar.2023.1263975

07:10

PubMed articles on: Cancer & VTE/PE

Complications of Central Venous Access Devices Used in Palliative Care Settings for Terminally Ill Cancer Patients: A Systematic Review and Meta-Analysis

Cancers (Basel). 2023 Sep 25;15(19):4712. doi: 10.3390/cancers15194712.

ABSTRACT

(1) Background: Central venous access devices (CVADs) have been commonly employed during various courses of anticancer treatment. Currently, there are a few types of clinically available CVADs, which are associated with short-term and long-term complications. However, little is known about the complication rates when CVADs are used only in palliative care settings. We therefore performed a systematic review and meta-analysis of all the published literature to evaluate the complication rates of CVADs in this clinical setting. (2) Methods: A systematic review and meta-analysis were conducted to identify publications from PubMed/MEDLINE, Embase (Ovid), Scopus, Cochrane Library, CINAHL, Google Scholar, and trial registries. Publications reporting the complication rates of PICCs, central lines, and PORTs in palliative settings for terminally ill cancer patients were included, while those on the use of systemic anticancer therapy and peripheral venous catheters were excluded. The outcome measures included overall complication rate, rate of catheter-related bloodstream infection (CRBSI), and rate of thromboembolism (TE). This systematic review was registered with PROSPERO (CRD42023404489). (3) Results: Five publications with 327 patients were analyzed, including four studies on PICCs and one study on central lines. No studies on PORTs were eligible for analysis. The overall complication rate for PICCs (pooled estimate 7.02%, 95% CI 0.27-19.10) was higher than that for central lines (1.44%, 95% CI 0.30-4.14, p = 0.002). The risk of CRBSI with PICCs (2.03%, 95% CI 0.00-9.62) was also higher than that with central lines (0.96%, 95% CI 0.12-3.41, p = 0.046). PICCs also had a trend of a higher risk of TE (2.10%, 95% CI 0.00-12.22) compared to central lines (0.48%, 95% CI 0.01-2.64, p = 0.061). (4) Conclusions: PICCs for palliative cancer care were found to have greater complications than central lines. This might aid in the formulation of future recommendation guidelines on the choice of CVAD in this setting.

PMID:37835406 | PMC:PMC10571956 | DOI:10.3390/cancers15194712

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PubMed articles on: Cancer & VTE/PE

Low-Dose Rivaroxaban to Prevent Recurrences of Venous Thromboembolism in Cancer: A Real-Life Experience with a Focus on Female Patients

J Clin Med. 2023 Oct 9;12(19):6427. doi: 10.3390/jcm12196427.

ABSTRACT

BACKGROUND: The way in which to prevent recurrent venous thromboembolism (VTE) is an unmet clinical need in cancer patients. International guidelines only provide conditional recommendations and do not specify which anticoagulant and dose should be used. In the last 2 years, we have been using low-dose rivaroxaban to prevent VTE recurrences in cancer patients. The results of this real-life experience are presented in this study.

METHODS: All patients had cancer and had previously completed a cycle of at least six months of full-dose anticoagulation for the treatment of a VTE index event, before receiving a prescription of low-dose rivaroxaban (10 mg once daily) for secondary prevention of VTE. Effectiveness and safety of this therapeutic regimen were evaluated in terms of VTE recurrences, major bleedings (MB), and clinically relevant non-major bleedings (CRNMB).

RESULTS: The analysis included 106 cancer patients. Their median age was 60 years (IQR 50-69). Metastatic cancer was present in 87 patients (82.1%). Six patients (5.7%) had brain metastases. Over a median follow-up time of 333 days (IQR 156-484), the incidence of VTE recurrences was 3.8% (95%CI 1.0-9.4), with a recurrence rate of 4.0 per 100 person-years (95%CI 1.1-10.2). We observed no MB (0.0%) and three CRNMB (2.8%) (95%CI 0.6-8.1).

CONCLUSIONS: Low-dose rivaroxaban is potentially effective and safe in cancer patients that require prevention of recurrent VTE. Large-scale studies are needed to confirm these findings.

PMID:37835070 | PMC:PMC10573527 | DOI:10.3390/jcm12196427

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PubMed articles on: Cancer & VTE/PE

Inhibition of Factor XI: A New Era in the Treatment of Venous Thromboembolism in Cancer Patients?

Int J Mol Sci. 2023 Sep 22;24(19):14433. doi: 10.3390/ijms241914433.

ABSTRACT

Direct oral anticoagulants against activated factor X and thrombin were the last milestone in thrombosis treatment. Step by step, they replaced antivitamin K and heparins in most of their therapeutic indications. As effective as the previous anticoagulant, the decreased but persistent risk of bleeding while using direct oral anticoagulants has created space for new therapeutics aiming to provide the same efficacy with better safety. On this basis, drug targeting factor XI emerged as an option. In particular, cancer patients might be one of the populations that will most benefit from this technical advance. In this review, after a brief presentation of the different factor IX inhibitors, we explore the potential benefit of this new treatment for cancer patients.

PMID:37833881 | PMC:PMC10572808 | DOI:10.3390/ijms241914433

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PubMed articles on: Cancer & VTE/PE

Enoxaparin for the long-term therapy of venous thromboembolism in patients with cancer and renal insufficiency

Thromb Haemost. 2023 Oct 13. doi: 10.1055/a-2191-7510. Online ahead of print.