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Pazopanib and renal cell carcinoma

Renee K McAlister, Jonathan Aston, Megan Pollack, Liping Du, Tatsuki Koyama, David D Chism
BACKGROUND: Pazopanib is an oral tyrosine-kinase inhibitor that is approved by the U.S. Food and Drug Administration for treatment of metastatic renal cell carcinoma (mRCC). Pharmacokinetic data have shown that concomitant administration of pazopanib and esomeprazole, a proton pump inhibitor (PPI), leads to decreased area under the curve and thus decreased exposure of pazopanib by 40%. Despite the pharmacokinetic data published to date, the clinical significance and impact on patient outcomes resulting from decreased pazopanib exposure remains unknown...
February 27, 2018: Oncologist
Michael W van Kalleveen, Maudy Walraven, Mathijs P Hendriks
Introduction Tumor lysis syndrome (TLS) is a life-threatening emergency caused by rapid cell death as a result of anti-tumor therapy. In the era of targeted therapy it has increasingly been observed in solid malignancies such as hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). Case We describe the case of a 58-year old man with the medical history of a memorial sloan kettering cancer centre (MSKCC) poor prognosis metastasized clear cell renal cell carcinoma (mRCC) who developed TLS within six days after initiating therapy with the tyrosine kinase inhibitor (TKI) pazopanib...
February 20, 2018: Investigational New Drugs
Annelies Verbiest, Gabrielle Couchy, Sylvie Job, Laure Caruana, Evelyne Lerut, Raymond Oyen, Aurélien de Reyniès, Lorenzo Tosco, Steven Joniau, Hendrik Van Poppel, Dirk Van Raemdonck, Kathleen Van Den Eynde, Agnieszka Wozniak, Jessica Zucman-Rossi, Benoit Beuselinck
BACKGROUND: Metastasectomy is routinely performed in selected patients with metastatic clear-cell renal cell carcinoma (ccRCC) as an alternative to systemic therapy. In the absence of randomized trials, the benefit and best way of patient selection remain unclear. Earlier, we described four molecular ccRCC-subtypes (ccrcc1-4) that have a prognostic and predictive value upon first-line sunitinib or pazopanib. OBJECTIVE: Assess the prognostic value of ccrcc1-4 subtypes after complete metastasectomy...
February 17, 2018: European Urology
Lin Yang, Anna Alyasova, Dingwei Ye, Antonia Ridolfi, Luca Dezzani, Robert J Motzer
BACKGROUND: RECORD-4 assessed everolimus in patients with metastatic renal cell carcinoma (mRCC) who progressed after 1 prior anti-vascular endothelial growth factor (VEGF) or cytokine and reinforced the clinical benefit of second-line everolimus. Because of the high percentage of patients from China enrolled in RECORD-4 (41%) and some reported differences in responses to certain targeted agents between Chinese and Western patients, this subanalysis evaluated outcomes in Asian versus non-Asian patients...
February 17, 2018: BMC Cancer
Marco Bandini, Ariane Smith, Michele Marchioni, Raisa S Pompe, Tristan F Martel, Luca Cindolo, Francesco Montorsi, Shahrokh F Shariat, Alberto Briganti, Anil Kapoor, Umberto Capitanio, Pierre I Karakiewicz
To conduct a review of literature on adjuvant therapy in nonmetastatic renal-cell carcinoma (nmRCC) treated with nephrectomy and to describe the efficacy of adjuvant agents on cancer control outcomes. A review of the literature was performed in January 2018 to identify all studies evaluating adjuvant therapy in patients with nmRCC treated with nephrectomy using PubMed, Embase, Medline, and Cochrane Library databases. The following keywords were used: adjuvant therapy, renal-cell carcinoma, nonmetastatic, targeted molecular therapy, kidney cancer...
February 2, 2018: Clinical Genitourinary Cancer
Arduino A Mangoni, Ganessan Kichenadasse, Andrew Rowland, Michael J Sorich
Background: There is inconsistency in the criteria used to define anti-vascular endothelial growth factor (VEGF) drug-induced hypertension (AVEGF-HT) in published studies. It is unknown whether specific patient characteristics similarly predict AVEGF-HT using different criteria. Methods: We assessed the associations between clinical and demographic factors (n = 22) and AVEGF-HT, using six criteria based on predefined on-treatment blood pressure (BP) thresholds or absolute BP elevations versus baseline, in a post hoc analysis of a phase III trial of 1102 patients with renal cell carcinoma (RCC) randomized to pazopanib or sunitinib (COMPARZ study)...
2018: Therapeutic Advances in Medical Oncology
Davis G Taylor, Adeel Ilyas, Gautam U Mehta, Ching-Jen Chen, David Schiff, Edward H Oldfield, Ashok R Asthagiri
Von Hippel-Lindau (VHL) disease is a multisystem genetic disease, the cardinal manifestations of which include central nervous system hemangioblastomas (CNS HB), renal cell carcinomas (RCC), and pheochromocytoma. Tumorigenesis in VHL of both RCC and CNS HB occurs secondary to downstream effects of a mutated or absent VHL protein. Treatment of RCCs with tyrosine kinase inhibitors (TKIs) such as Pazopanib is now first line therapy, but their effect on VHL-associated CNS HBs remains unknown. We report the use of Pazopanib in a patient with VHL disease for treatment of RCC who also harbored multiple CNS HBs...
January 26, 2018: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Bulent Cetin, Guldal Esendagli Yılmaz, Berkan Armagan, Baris Afsar, Umut Demirci, Ozlem Gulbahar, Ozge Gumusay, Irem Bilgetekin, Ahmet Ozet, Aytug Uner
Pazopanib is an effective treatment for advanced renal cell carcinoma and soft tissue sarcoma. Besides classical adverse events of this drug class, hepatotoxicity has been described as a frequent side effect. The aim of the present study was to evaluate the effect of pazopanib on the liver in an experimental rat model. Sixteen Wistar albino rats were divided into 3 groups: experimental toxicity was induced with pazopanib (10 mg/kg) administered for 28 days (group 2) or 56 days (group 3) orally by gavage. Group 1 (control group) received only distilled water...
January 24, 2018: Chemotherapy
Diogo Alpuim Costa, Susana Baptista de Almeida, Pedro Coelho Barata, António Quintela, Pedro Cabral, Ana Afonso, João Maia Silva
In phase II/III trials, cutaneous side effects of pazopanib were reported in less than 20% of patients, with only 1-3% being grade 3/4. We present a case of a 66-year-old man with a previous history of left nephrectomy for a stage II clear cell renal carcinoma. Approximately 18 months later, recurrent disease in the lungs, mediastinum, and left psoas and bulky abdominal/pelvic nodal metastasis were documented. He was initially treated with pazopanib 800 mg q.d. and 1 week after starting this therapy, the patient presented with palpable purpura on his ankles...
September 2017: Case Reports in Oncology
Arie J Verschoor, Fabiënne A R M Warmerdam, Tjalling Bosse, Judith V M G Bovée, Hans Gelderblom
BACKGROUND: Pazopanib is an oral tyrosine kinase inhibitor registered for metastatic renal cell carcinoma and soft tissue sarcoma. Liver toxicity is a common side effect for this class of agents. The current opinion is that in case of severe liver toxicity pazopanib should be interrupted and restarted at a lower dose after returning to Common Terminology Criteria for Adverse Events (CTCAE) grade 1. After recurrence of liver toxicity at the lower dose it is advised to permanently stop pazopanib...
January 22, 2018: BMC Cancer
Cora Sternberg, Frede Donskov, Naomi B Haas, Christian Doehn, Paul Russo, Mohamed A Elmeliegy, Guillaume Baneyx, Hiya Banerjee, Paola Aimone, Robert J Motzer
PURPOSE: PROTECT, a phase III randomized placebo-controlled study, evaluated pazopanib efficacy and safety in the adjuvant RCC setting. The relationship between pazopanib exposure (Ctrough) and efficacy and safety was evaluated. EXPERIMENTAL DESIGN: Evaluable steady-state blood trough concentrations were collected from 311 patients at week 3 or 5 (early Ctrough), and 250 patients at week 16 or 20 (late Ctrough). Pazopanib pharmacokinetic (PK) data was analyzed via a population model approach...
January 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Harvey Yu-Li Su
No abstract text is available yet for this article.
December 21, 2017: Clinical Genitourinary Cancer
Anne Robdrup Tinning, Camilla Bengtsen, Niels Viggo Jensen, Lars Bastholt, Boye Lagerbon Jensen, Kirsten Madsen
Drugs targeting VEGF (vascular endothelial growth factor) are often associated with rapid development of hypertension by a yet not fully understood mechanism. VEGF is expressed in renal epithelial cells and stimulates NO production. In the renal medulla, inhibition of NO formation by local L-NAME or by impaired endothelin-1 leads to hypertension. The present study was designed to test the hypothesis that VEGF receptor inhibitor treatment leads to hypertension through decreased renal medullary formation of NO and endothelin-1...
January 8, 2018: Hypertension
Shinya Takasaki, Masaki Tanaka, Masafumi Kikuchi, Masamitsu Maekawa, Yoshihide Kawasaki, Akihiro Ito, Yoichi Arai, Hiroaki Yamaguchi, Nariyasu Mano
An analytical method using high performance liquid chromatography/electrospray ionization tandem mass spectrometry has been developed and validated for simultaneous measurement of four tyrosine kinase inhibitors used for renal cell carcinoma and their metabolites in human plasma. Despite their similar structures, it is difficult to measure plasma levels of these compounds simultaneously using optimal MS parameters for each compound because a quantitative range exceeding 50,000-fold is required. To overcome this problem, we used a linear range shift technique using in-source collision-induced dissociation...
December 28, 2017: Biomedical Chromatography: BMC
Jennifer M Logue, Bahram Kiani, Rhonda L Bitting
Background: The VEGF inhibitor pazopanib is a widely used first-line therapy for the treatment of advanced renal cell carcinoma. Potential drug-drug interactions and toxicities may be underrecognized. Case Presentation: A 73-year-old woman with metastatic renal cell carcinoma on treatment with pazopanib presented with progressive inability to ambulate. The initial concern was for metastasis to the spine. However, MRI of the spine revealed diffuse muscle edema with no metastatic deposits or lytic lesions...
September 2017: Case Reports in Oncology
Miguel A Climent, José Muñoz-Langa, Laura Basterretxea-Badiola, Carmen Santander-Lobera
A systematic review was conducted to identify real world studies reporting outcomes after first-line pazopanib in patients with metastatic renal cell carcinoma. Studies had to be observational and report survival data in terms of progression-free survival and overall survival in order to conduct meta-analysis techniques. These real-world data were compared to those obtained in the phase II and III randomized controlled trials of pazopanib. Real world evidence showed that the clinical and safety outcomes were consistent with those observed in the clinical trials despite the inclusion of unselected patients with a wide spectrum of prognostic features and comorbidities...
January 2018: Critical Reviews in Oncology/hematology
Alexandr Poprach, Ondrej Fiala, Renata Chloupkova, Bohuslav Melichar, Radek Lakomy, Katarina Petrakova, Milada Zemanova, Katerina Kopeckova, Ondrej Slaby, Hana Studentova, Jindrich Kopecký, Igor Kiss, Jindrich Finek, Ladislav Dusek, Tomas Buchler
BACKGROUND: Pazopanib is approved for the first-line treatment of patients with metastatic renal cell carcinoma (mRCC). The present study was a retrospective registry-based analysis of 426 patients with mRCC treated with pazopanib as first-line targeted therapy. PATIENTS AND METHODS: The data were obtained from the Renal Cell Carcinoma Information system registry. Patient baseline parameters, treatment course and outcomes, and toxicity were analysed. RESULTS: Median progression-free and overall survival were 12...
January 2018: Anticancer Research
Lindsay Wilde, Praveen Mehrotra, Jean Hoffman-Censits
A 73-year-old male with a remote history of renal cell carcinoma presented with an asymptomatic left ventricular mass. Biopsy of the mass revealed a late recurrence of his renal cell carcinoma. Given the size and location of the mass, resection was not possible. Treatment with pazopanib was initiated with good clinical response.
December 2017: Canadian Journal of Urology
Annelies Verbiest, Gabrielle Couchy, Sylvie Job, Jessica Zucman-Rossi, Laure Caruana, Evelyne Lerut, Raymond Oyen, Aurélien de Reyniès, Brigitte Laguerre, Nathalie Rioux-Leclercq, Agnieszka Wozniak, Steven Joniau, Hendrik Van Poppel, Kathleen Van Den Eynde, Benoit Beuselinck
BACKGROUND: We previously described 4 molecular subtypes of metastatic clear cell renal cell carcinoma (mccRCC), named ccrcc1-4 (Beuselinck et al, 2015). These have both prognostic and predictive value for patients treated with first-line sunitinib, with distinctive objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The ccrcc2 and ccrcc3 tumors have the best outcomes, followed by ccrcc1 and then ccrcc4. We hypothesized that these molecular subtypes would show similar outcomes with first-line pazopanib treatment...
November 7, 2017: Clinical Genitourinary Cancer
John Kucharczyk, Kamal Mandalapu, Suma Satti, Marc R Matrana
Background: Late relapse with presentation of metastatic disease >5 years after nephrectomy with curative intent is a known behavior of renal cell carcinoma (RCC), but data on outcomes, especially regarding targeted therapies, are limited. In this study, we analyze clinicopathologic features and response to targeted therapy in patients with late-relapse metastatic RCC (mRCC). Methods: We retrospectively reviewed clinical data on consecutive patients treated with targeted therapy for mRCC diagnosed >5 years after nephrectomy with curative intent...
2017: Ochsner Journal
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