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    Could the concomitant use of beta blockers with bevacizumab improve survival in metastatic colon cancer?
    (Springer Heidelberg, 2023) Kocak, Mehmet Zahid; Er, Muhiddin; Ugrakli, Muzaffer; Hendem, Engin; Araz, Murat; Eryilmaz, Melek Karakurt; Artac, Mehmet
    AimDrug-drug interactions are sometimes neglected in oncology practice. Due to drug pharmacokinetic and pharmacodynamic interactions, clinically increased or decreased drug effects and increased or decreased adverse effects may occur. Considering that the concomitant use of these two drugs that affect vascular endothelial growth factor receptor (VEGFR) may cause pharmacological potentiation or additive interaction, we aimed to evaluate the survival outcomes of concomitant use of bevacizumab and beta blockers in patients with metastatic colorectal cancer (mCRC).MethodsIn total, 181 patients with mCRC administered with bevacizumab plus cytotoxic chemotherapy regimen in a first-line setting were divided into two groups: concomitant beta-blocker user and nonuser.ResultsThe median overall survival (mOS) was 35.9 (95% CI: 27.9-43.9) months in the beta-blocker-using group and 29.6 (95% CI: 27.9-43.9) months in the beta-blocker-non-using group (p = 0.054). The median progression-free survival (mPFS) was 16.1 (95% CI: 12.4-19.9) months in the beta-blocker-using group and 12.8 (95% CI: 10.6-15.0) months in the beta-blocker-non-using group (p = 0.006). The multivariate analysis revealed that beta-blocker use was an independent predictor of mPFS (HR: 0.66, 95% CI: 0.46-0.93, p = 0.018) and mOS (HR: 0.57, 95% CI: 0.36-0.91, p = 0.02).ConclusionThis study demonstrated that concomitant usage of beta blockers improved both survival outcomes, irrespective of the kind of beta blocker.
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    The effect of concomitant proton pump inhibitor use on survival outcomes of Nivolumab-treated renal cell carcinoma patients: a multicenter study
    (Springer, 2023) Ugrakli, Muzaffer; Kocak, Mehmet Zahid; Dinc, Gulhan; Genc, Tugrul Burak; Caglayan, Melek; Ugrakli, Selin; Hendem, Engin
    AimWe aimed to evaluate the effect of concomitant proton pump inhibitors (PPI) use with nivolumab on survival outcomes in metastatic renal cell carcinoma (mRCC) in second-line setting.MethodsThe study was designed as a multicenter and retrospective involving patients with metastatic renal cell carcinoma receiving second-line nivolumab therapy. One hundred and nine patients with mRCC were divided into two groups based on whether they use PPI concomitantly with nivolumab: concomitant PPI users and non-users. Overall survival (OS) and progression-free survival (PFS) were compared between the groups with and without concurrent PPIs.ResultsOf 109 patients in our study, 59 were not using PPI concomitantly with nivolumab and 50 were using PPI concomitantly. The median PFS was 6.37 (5.2-7.5) months in the concomitant PPI group and 9.7 (4.5-15) months in the non-users (p = 0.03). The median OS was 14.6 (7.1-22.1) months in patients on PPI concurrently with nivolumab and 29.9 (17.1-42.7) months in the non-users (p = 0.01). Accordingly, PPI use for PFS (Non-use vs. Use = HR: 0.44, 95%Cl 0.28-0.96, p = 0.014) and PPI use for OS (Non-use vs. Use = HR: 0.68, 95%Cl 0.22-0.88, p = 0.01) were found to be as independent risk factors.ConclusionsConcomitant use of PPIs is associated with worse survival outcomes in patients with mRCC treated with nivolumab. Clinicians should carefully consider the concomitant use of PPIs in such patients.
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    Pazopanib-associated secondary adrenal insufficiency in a patient with malignant solitary fibrous tumor
    (Sage Publications Ltd, 2021) Er, Muhammed Muhiddin; Araz, Murat; Karabacak, Meryem; Ugrakli, Muzaffer; Eryilmaz, Melek Karakurt; Karaagac, Mustafa; Artac, Mehmet
    Introduction Pazopanib is an agent that is being successfully used in soft tissue sarcomas. Some endocrine side effects may develop during pazopanib treatment. Here, we presented a case diagnosed with secondary adrenal insufficiency while being investigated for etiology of hypoglycemia which developed after pazopanib. Case report A 69-year-old male patient was operated in June 2019 due to a lung mass 26 x 18 x 10 cm in size. Pathological diagnosis revealed a solitary fibrous tumor with malignant behavior. The patient received three lines of chemotherapy. After pazopanib treatment, a hypoglycemic attack was reported. Management and outcome: Blood cortisol and ACTH (Adrenocorticotropic hormone) levels were not increased at the time of the hypoglycemic attack, and levels of other pituitary hormones were found to be normal. Electrolyte levels were in normal range. Since the counteracting hormone did not reach a sufficient level, it was considered secondary adrenal insufficiency. Hypoglycemic attacks did not occur during follow-up while taking steroid therapy and pazopanib. Discussion A single case of primary adrenal insufficiency has been reported in the literature. We here present a case who developed hypoglycemia after pazopanib and was diagnosed with drug-associated secondary adrenal insufficiency. When hypoglycemia develops during pazopanib treatment, we must be aware of adrenal insufficiency.
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    Pneumonitis associated with Trastuzumab emtansine in a patient with metastatic breast cancer
    (Sage Publications Ltd, 2022) Ugrakli, Muzaffer; Araz, Murat; Demirkiran, Aykut; celik, Ahmet Faruk; Karakurt Eryilmaz, Melek; Karaagac, Mustafa; Artac, Mehmet
    Introduction Trastuzumab emtansine (TDM-1) is an antibody-drug conjugate effective in human epidermal growth factor receptor-2 - expressing advanced breast cancer. Pulmonary complications of TDM-1 are rarely reported. TDM-1-associated interstitial lung disease is referred to as pneumonitis. Case report A 47-year-old female patient who underwent modified radical mastectomy and axillary lymph node dissection operations due to a palpable mass in the right breast and axillary region. The patient who had received multiple chemotherapy was last receiving TDM-1 treatment. Fatigue, dyspnea, and tachypnea were detected for the first time on 20 days after the 6(th) treatment. Menagement and outcome In our case, we first considered metastasis, pneumonia and fungal infection based on radiological findings, but the lack of response to the treatments and the results of the investigations suggested drug-induced pneumonia and steroid treatment was started. Our case had a complete radiological recovery and complete response to sterod therapy. In such cases, it is important to first exclude infections and metastasis. In cases of drug-induced pneumonia, the first treatment option is systemic corticosteroids and generally responded well. Discussion Unlike other cases of interstitial pneumonia, lung imaging of our case was resembling a metastasis, pneumonia and fungal infection. With increasing use of TDM-1, we will have more experience in both efficacy and complications of TDM-1. Although TDM-1 is a well-tolerated drug, clinicians should be aware of rare pulmonary complications and prepared to respond appropriately.