Introduction: Despite first-line approval in metastatic renal cell carcinoma (mRCC), the tyrosine kinase inhibitor cabozantinib is associated with frequent treatment-limiting side effects. Dose reductions in published trials of the drug and in clinical practice are commonplace. We analyzed our institution's real-world experience with cabozantinib dosing in patients with mRCC to assess strategies to improve tolerability and patient outcomes.
Objectives: The purpose of our study is to retrospectively analyze dose intensity, tolerability, and duration of exposure in mRCC patients who received cabozantinib at our institution.
Methods: In this retrospective, single-center chart review, we identified 35 adult patients who received at least one cycle cabozantinib for mRCC during a two-year period. Dosing patterns were reviewed for each patient to allow calculation of median dose intensity and median duration of exposure.
Results: The median dose intensity for cabozantinib was 55.4% and the median actual daily dose was 33.2 mg. Median duration of cabozantinib exposure was 10.4 months. Several alternative dosing strategies were employed with 60% of patients requiring at least one dose intervention to manage toxicities.
Conclusions: Patients in this analysis received a median actual daily dose of 33.4 mg, less than the reported median doses in the METEOR and CABOSUN trials. However, our median duration of cabozantinib treatment was 10.4 months compared to 8.3 months and 6.5 months in these respective trials. Further investigation is warranted to determine if alternative dosing strategies and lower median actual daily doses produce survival results comparable to published clinical trials.
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http://dx.doi.org/10.1177/1078155219875509 | DOI Listing |
Pharmacol Res
January 2025
Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai, China. Electronic address:
Biased µ-opioid receptor (MOR) agonists enhance pain relief by selectively activating G protein-coupled receptor signaling and minimizing β-arrestin-2 activation, resulting in fewer side effects. This multicenter Phase II/III trial evaluated the optimal dosage, efficacy, and safety of SHR8554, a biased MOR agonist, for postoperative pain management following orthopedic surgery. In Phase II, 121 patients were divided into four groups to receive varying patient-controlled analgesia (PCA) doses of SHR8554 or morphine.
View Article and Find Full Text PDFCancer Chemother Pharmacol
January 2025
Clinical Pharmacology and Translational Sciences, Pfizer Worldwide R&D, 10555 Science Center Drive, San Diego, CA, 92121, USA.
As development of new oncology small molecule therapies is focused mainly on molecularly targeted agents, the dose selection paradigm has shifted from the maximum tolerated dose (MTD)-based approach traditionally utilized with cytotoxic drugs towards determining an optimal dose with long-term tolerability while maintaining efficacy. To assess overall tolerability in recently approved oncology small molecules, we surveyed 54 compounds approved by the FDA since March 2017 with respect to dose intensity, dose modifications, and treatment emergent adverse events (TEAEs). Of the 54 new molecular entities surveyed, only 15 were approved at a label dose equal to the MTD (Label Dose = MTD).
View Article and Find Full Text PDFUltrasound Med Biol
January 2025
Department of Ultrasound, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address:
Objective: To evaluate the added value of dynamic contrast-enhanced ultrasound (DCE-US) analysis in pre-operative differential diagnosis of small (≤20 mm) solid pancreatic lesions (SPLs).
Methods: In this retrospective study, patients with biopsy or surgerical resection and histopathologically confirmed small (≤20 mm) SPLs were included. One wk before biopsy/surgery, pre-operative B-mode ultrasound and contrast-enhanced ultrasound were performed.
Clin Investig Arterioscler
January 2025
Unidad de Cardiología, Hospital Universitario de Jaén, Jaén, España.
Objective: To estimate the clinical and economic benefits derived from increasing the use of fixed-dose combinations of high-intensity statins and ezetimibe in patients at high/very high cardiovascular risk, from the perspective of the Spanish National Health System (SNS).
Methods: A baseline scenario (current market shares) was compared with scenarios that increased the use of fixed-dose combinations (alternative: 30% increase; optimized: 69% increase). The potential annual increase in the number of controlled patients, cardiovascular events avoided and the associated savings in direct medical costs were estimated, including the cost of pharmacological treatment, follow-up, and managing cardiovascular events over a three-year time horizon.
Phys Med
January 2025
Department of Radiation Oncology, The Third Affiliated Hospital, Sun Yan-Sen University, Guangzhou 510630, China. Electronic address:
A preliminary study was conducted using electronic portal imaging device (EPID) based dose verification in pre-treatment and in vivo dose reconstruction modes for breast cancer intensity-modulated radiation therapy (IMRT) technique with known repositioning set-up errors. For 43 IMRT plans, the set-up errors were determined from 43 sets of EPID images and 258 sets of cone beam computed tomography images. In-house developed Edose software was used to reconstruct the dose distribution using the pre-treatment and on-treatment (in vivo) EPID acquired fluence maps.
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