Nephrectomy is the reference-standard treatment for renal-cell carcinoma (RCC). For patients with unresectable disease, tumor may be shrunk by using chemotherapy, thereby permitting surgical resection, which can be curative. We provided neoadjuvant cabozantinib, the preferred tyrosine kinase inhibitor for advanced RCC of poor and intermediate risk, to two patients with initially unresectable RCCs. In both patients, this led to tumor shrinkage of > 50% after 4 months of therapy, which permitted surgical resection. Both tumor specimens also showed strong pathologic tumor response. The robust responses observed with cabozantinib, even at reduced doses, suggest it to be an effective neoadjuvant option in RCC. Our novel experience with neoadjuvant cabozantinib, combined with our review of the use of cabozantinib in RCC, indicates that providing preoperative cabozantinib to facilitate potentially curative surgical resection has good results and should be further explored.
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http://dx.doi.org/10.1016/j.clgc.2020.04.003 | DOI Listing |
Res Sq
August 2024
Winship Cancer Institute, Emory University, Atlanta, GA, USA.
Cabozantinib is an oral multikinase inhibitor approved for treatment in metastatic renal cell carcinoma (RCC). We hypothesized that neoadjuvant cabozantinib could downstage localized tumors, facilitating partial nephrectomy, and facilitating surgery in patients with locally advanced tumors that would require significant adjacent organ resection. We, therefore, conducted a phase 2, single-arm trial of cabozantinib treatment for 12 weeks in 17 patients with locally advanced biopsy-proven non-metastatic clear cell RCC before surgical resection.
View Article and Find Full Text PDFCancer Med
January 2024
Department of Pediatric Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Introduction: Introduction: Renal cell carcinoma (RCC) is a very rare pediatric renal tumor. Robust evidence to guide treatment is lacking and knowledge on targeted therapies and immunotherapy is mainly based on adult studies. Currently, the International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG) 2016 UMBRELLA protocol recommends sunitinib for metastatic or unresectable RCC.
View Article and Find Full Text PDFThe treatment paradigm for high risk localized and advanced kidney cancer has been characterized by ongoing changes, with the introduction of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) and later with immune checkpoint blockade. In this article, we review how current evidence informs our decision-making on post-checkpoint inhibitor systemic therapies, the role of adjuvant and/or neoadjuvant therapies, and the role of cytoreductive nephrectomy in the evolving systemic therapy landscape. While some studies support a post-checkpoint inhibitor benefit from the VEGFR TKIs cabozantinib or axitinib, the benefit of doublet therapies including a VEGF receptor inhibitor and a checkpoint inhibitor remains an area of active investigation, with the combination of lenvatinib plus pembrolizumab showing promise but with a Phase III trial of the combination of atezolizumab plus cabozantinib showing no benefit over cabozantinib alone.
View Article and Find Full Text PDFFront Oncol
June 2024
Department of Hepatobiliary and Pancreatic Surgery I, General Surgery Center, The First Hospital of Jilin University, Changchun, China.
Hepatocellular carcinoma (HCC), a type of liver cancer, ranks as the sixth most prevalent cancer globally and represents the third leading cause of cancer-related deaths. Approximately half of HCC patients miss the opportunity for curative treatment and are then limited to undergoing systemic therapies. Currently, systemic therapy has entered the era of immunotherapy, particularly with the advent of immune-checkpoint inhibitors (ICIs), which have significantly enhanced outcomes for patients with advanced HCC.
View Article and Find Full Text PDFCancer Res
August 2024
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Due to the lack of treatment options, there remains a need to advance new therapeutics in hepatocellular carcinoma (HCC). The traditional approach moves from initial molecular discovery through animal models to human trials to advance novel systemic therapies that improve treatment outcomes for patients with cancer. Computational methods that simulate tumors mathematically to describe cellular and molecular interactions are emerging as promising tools to simulate the impact of therapy entirely in silico, potentially greatly accelerating delivery of new therapeutics to patients.
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