Neoadjuvant pazopanib and molecular analysis of tissue response in renal cell carcinoma

Wood, Christopher G.; Ferguson, James E.; Parker, Joel S.; Moore, Dominic T.; Whisenant, Jennifer G.; Maygarden, Susan J.; Wallen, Eric; Kim, William Y.; Milowsky, Mathew I.; Beckermann, Kathryn E.; Davis, Nancy B.; Karam, Jose A.; Bortone, Dante S.; Vincent, Benjamin G.; Powles, Thomas; Rathmell, W. Kimryn

doi:10.1172/jci.insight.132852

Cited by 13 publications

(6 citation statements)

References 48 publications

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“…Currently, pazopanib has been approved in the EU, the USA, and other nations for the treatment of advanced RCC ( 35 ). In addition, several prospective clinical trials and retrospective studies support the use of pazopanib as a standard or alternative first-line treatment for advanced or metastatic RCC ( 35 – 37 ).…”

Section: Discussionmentioning

confidence: 99%

Case Report: Pancreatic metastasis of renal cell carcinoma 16 years after nephrectomy

Lou

Guo²,

Zheng³

2023

Front. Oncol.

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BackgroundRenal cell carcinoma (RCC) is the most common renal malignancy, and may metastasize to different sites in the body via hematogenous and lymphomatous routes. The pancreas is a rare metastatic site of metastatic RCC (mRCC) and isolated pancreatic metastasis of RCC (isPMRCC) is even rarer.ResultsThe present report describes a case of isPMRCC that recurred 16 years after surgery. The patient responded well to the treatment with pancreaticoduodenectomy and systemic therapy, and no recurrence was recorded after 2 years.ConclusionsisPMRCC is a distinct subgroup of RCC with unique clinical characteristics that may be explained by its underlying molecular mechanisms. Surgery and systemic therapy confer survival benefits to patients with isPMRCCs, although the recurrence problem has to be paid attention to.

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Section: Discussionmentioning

confidence: 99%

Case Report: Pancreatic metastasis of renal cell carcinoma 16 years after nephrectomy

Lou

Guo²,

Zheng³

2023

Front. Oncol.

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“…Bevacizumab has been used for CaCx treatment in many clinical trials that led to its approval, and continues to be used, with good patient prognosis despite its high toxicity levels in some cases according to expert opinion. A tyrosine kinase inhibitor (TKI), pazopanib also directly affects VEGF and is currently used for renal cell carcinoma and other soft-tissue tumors though not currently approved for CaCx [ 71 , 72 ].…”

Section: Cancer Hallmarks Targetable By Innocuous Integrative Oncologymentioning

confidence: 99%

Biological Therapy with Complementary and Alternative Medicine in Innocuous Integrative Oncology: A Case of Cervical Cancer

Chizenga

Abrahamse

2021

Pharmaceutics

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Good medicine is based on good science, inquiry driven and open to new paradigms. For a complex disease such as cancer, a complex treatment regime that is well structured and multifactorial is indispensable. In the present day, Complementary and Alternative Medicine (CAM) therapies are being used frequently for cancer, alongside modern biological therapies and allopathic medicine, in what is called integrative oncology. In all conscience, the use of natural, less invasive interventions whenever possible is ideal. However, a comprehensive understanding of not only the etiopathology of individual cancers, but also the detailed genetic and epigenetic characteristics, the cancer hallmarks, that clearly show the blueprint of the cancer phenotype is a requisite. Different tumors have a common behavioral pattern, but their specific features at the genetic and epigenetic levels vary to a great extent. Henceforth, with so many failed attempts to therapy, drug formulations and combinations need a focused pre-assessment of the inherent features of individual cancers to destroy the tumors holistically by targeting these features. This review therefore presents innocuous therapeutic regimes by means of CAM and integrative medicine approaches that can specifically target the hallmarks of cancer, using the case of cervical cancer.

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“…Results were most favourable for sunitinib and axitinib [ 5 , 7 , 11 ]. There are several prospective studies on VEGFR TKIs in the pre-nephrectomy setting [ 13 – 15 ], but none specifically addresses the question of surgical downstaging of vein-involved local extension. Wood et al reported on four patients with IVC VTT but reported no change in surgical management, and did not report specifically about change in the extent of venous involvement [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…There are several prospective studies on VEGFR TKIs in the pre-nephrectomy setting [ 13 – 15 ], but none specifically addresses the question of surgical downstaging of vein-involved local extension. Wood et al reported on four patients with IVC VTT but reported no change in surgical management, and did not report specifically about change in the extent of venous involvement [ 13 ]. In a Phase II trial of 12 weeks of neoadjuvant axitinib in clear cell RCC (ccRCC; all patients were cT3a), the median reduction in primary tumour diameter was 28% [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

A Phase II study of neoadjuvant axitinib for reducing the extent of venous tumour thrombus in clear cell renal cell cancer with venous invasion (NAXIVA)

et al. 2022

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Background Surgery for renal cell carcinoma (RCC) with venous tumour thrombus (VTT) extension into the renal vein (RV) and/or inferior vena cava (IVC) has high peri-surgical morbidity/mortality. NAXIVA assessed the response of VTT to axitinib, a potent tyrosine kinase inhibitor. Methods NAXIVA was a single-arm, multi-centre, Phase 2 study. In total, 20 patients with resectable clear cell RCC and VTT received upto 8 weeks of pre-surgical axitinib. The primary endpoint was percentage of evaluable patients with VTT improvement by Mayo level on MRI. Secondary endpoints were percentage change in surgical approach and VTT length, response rate (RECISTv1.1) and surgical morbidity. Results In all, 35% (7/20) patients with VTT had a reduction in Mayo level with axitinib: 37.5% (6/16) with IVC VTT and 25% (1/4) with RV-only VTT. No patients had an increase in Mayo level. In total, 75% (15/20) of patients had a reduction in VTT length. Overall, 41.2% (7/17) of patients who underwent surgery had less invasive surgery than originally planned. Non-responders exhibited lower baseline microvessel density (CD31), higher Ki67 and exhausted or regulatory T-cell phenotype. Conclusions NAXIVA provides the first Level II evidence that axitinib downstages VTT in a significant proportion of patients leading to reduction in the extent of surgery. Clinical trial registration NCT03494816.

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Neoadjuvant pazopanib and molecular analysis of tissue response in renal cell carcinoma

Cited by 13 publications

References 48 publications

Case Report: Pancreatic metastasis of renal cell carcinoma 16 years after nephrectomy

Case Report: Pancreatic metastasis of renal cell carcinoma 16 years after nephrectomy

Biological Therapy with Complementary and Alternative Medicine in Innocuous Integrative Oncology: A Case of Cervical Cancer

A Phase II study of neoadjuvant axitinib for reducing the extent of venous tumour thrombus in clear cell renal cell cancer with venous invasion (NAXIVA)

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