Severe sunitinib-induced myelosuppression in a patient with a CYP 3A4 polymorphism

2017 ◽  
Vol 24 (8) ◽  
pp. 623-626 ◽  
Author(s):  
Nirav D Patel ◽  
Kanishka Chakrabory ◽  
Garrett Messmer ◽  
Koyamangalath Krishnan ◽  
John B Bossaer
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Growth Factor Receptor ◽  
Skin Reactions ◽  
Current State ◽  
Early Grade ◽  
Grade 3 ◽  
Endothelial Growth Factor

Sunitinib, an oral vascular endothelial growth factor receptor, is a first-line option for metastatic renal cell carcinoma and widely used in clinical practice. Despite the proven benefit of sunitnib in metastatic renal cell carcinoma, patients may suffer from a variety of adverse events including hypertension, fatigue, hypothyroidism, hand–foot skin reactions, rash, depigmentation, and myelosuppression. Myelosuppression is usually mild, transient and resolves during the two weeks at the end of each cycle where no drug is taken. We present a case of severe and early grade 3 neutropenia and thrombocytopenia occurring two weeks into a six-week cycle. Because of the extreme nature of the toxicity, CYP 3A4 polymorphisms were explored. The patient was found to be heterozygous for CYP 3A4*22, at least partially explaining the early-onset and severity of myelosuppression. This pharmacogenetics information resulted in a rechallenge of dose-reduced sunitinib, which was well tolerated by the patient. The current state of pharmacogenomics concerning sunitinb is also presented, and the need for greater research in this area is highlighted.

Treatment Strategies in Metastatic Renal Cell Carcinoma

2010 ◽  
Vol 06 (02) ◽  
pp. 41
Author(s):  
Alain Ravaud ◽  
Jean Christophe Bernhard ◽  
Marine Gross-Goupil ◽  
◽  
◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Mammalian Target Of Rapamycin ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Clinical Effects ◽  
Improved Outcomes ◽  
Endothelial Growth Factor

Metastatic renal cell carcinoma (mRCC) is associated with a poor clinical outcome. Until recently, treatment recommendations were limited to immunotherapy and nephrectomy; however, an increased understanding of the molecular biology of RCC has led to the advent of targeted therapies directed against vascular endothelial growth factor/receptor (VEGF/VEGFR) or the mammalian target of rapamycin (mTOR) pathways, both major mediators of tumour growth and progression. These targeted agents have significantly improved outcomes in patients with mRCC, revolutionising treatment. These treatments have overlaps and important distinctions in terms of clinical effects, toxicity and patient populations in which they have been investigated. Concerns in terms of the appropriate sequencing of these agents, their combined use and their role in the context of nephrectomy have emerged as clinically relevant and are being actively investigated.

scholarly journals Cabozantinib in metastatic renal cell carcinoma: latest findings and clinical potential

2017 ◽  
Vol 9 (10) ◽  
pp. 627-636 ◽  
Author(s):  
Melissa Bersanelli ◽  
Sebastiano Buti
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Wide Spectrum ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Immune Checkpoint Blockade ◽  
Endothelial Growth Factor

Since the advent of immunotherapy revolutionized the treatment of metastatic renal cell carcinoma (mRCC), the attention of oncologists has been unavoidably shifted from tyrosine kinase inhibitors (TKIs) to immune checkpoint blockade, with the associated risk of listing cabozantinib as just one of many available TKIs. On the contrary, we think that cabozantinib represents a very good option for mRCC treatment, with outstanding outcomes in terms of response rate, progression-free survival, overall survival and quick time to treatment response. Its safety profile is acceptable and its discontinuation rate, due to toxicity, is similar to those of other TKIs. It is still not clear if the effectiveness of this drug is justified by its wide spectrum of multikinase activity, extended to the MET and AXL kinases, or by the simple maintenance of a ‘vascular endothelial growth factor receptor pressure’ after another previous TKI. Early-phase studies are currently ongoing to investigate the potential activity and safety of cabozantinib in association with immunotherapy, albeit with the risk of an overly toxic combination. Thus, future opportunities to improve the clinical use of this drug will probably be represented by a smart treatment sequence.

scholarly journals Brain Complete Response to Cabozantinib prior to Radiation Therapy in Metastatic Renal Cell Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-4 ◽  
Author(s):  
An Uche ◽  
Chad Sila ◽  
Tad Tanoura ◽  
James Yeh ◽  
Neil Bhowmick ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Radiation Therapy ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Complete Response ◽  
Heavily Pretreated ◽  
Treatment Paradigm ◽  
Endothelial Growth Factor

Cabozantinib represents an established vascular endothelial growth factor- (VEGF-) tyrosine kinase inhibitor (TKI) in the treatment paradigm of metastatic renal cell carcinoma (mRCC). Its activity in mRCC patients with brain metastases (BMs) has been largely underreported in prospective clinical trials. We present the unique case of a heavily pretreated mRCC patient with BMs who achieved a brain complete response to cabozantinib prior to receiving radiation therapy. We end with a literature review and discussion of the biologic rationale and growing evidence supporting the intracranial activity of cabozantinib.

scholarly journals Impaired Retinal Circulation during Axitinib Treatment for Metastatic Renal Cell Carcinoma

2019 ◽  
Vol 10 (1) ◽  
pp. 5-10 ◽  
Author(s):  
Masashi Kimura ◽  
Sentaro Kusuhara ◽  
Mizuki Tagami ◽  
Makoto Nakamura
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Sudden Onset ◽  
Fundus Photography ◽  
Retinal Circulation ◽  
Circulatory Disorder ◽  
The Right ◽  
Endothelial Growth Factor

Purpose: Axitinib, an orally administered vascular endothelial growth factor receptors 1, 2, and 3 inhibitor, is widely used as the second-line treatment for metastatic renal cell carcinoma. We present a case of metastatic renal cell carcinoma who developed a novel ocular adverse event, impaired retinal circulation, during axitinib therapy. Methods: This is an observational case report. Results: A 57-year-old male who had been treated with axitinib for metastatic renal cell carcinoma for 2 years presented in August 2015. He complained of sudden-onset abnormal visual field in his right eye. His right eye exhibited multiple soft exudates on fundus photography and a significant fluorescein filling delay of the retinal vessels on fluorescein angiography. His best corrected visual acuity (BCVA) was 20/20 in the right eye, and a cecocentral scotoma was detected by Goldmann perimeter. As axitinib could have been responsible for impaired retinal circulation, axitinib was terminated and switched to temsirolimus. The soft exudates gradually subsided and the patients’ symptoms got better, but his right BCVA dropped to 20/63 3 months after the end of axitinib treatment with worsening of his general condition. Conclusion: Clinicians should be aware of retinal circulatory disorder that can occur in patients under axitinib treatment.

scholarly journals Papillary renal cell carcinoma: what is missing in research? A case report and a review of literature

2019 ◽  
Vol 7 ◽  
pp. 2050313X1986947 ◽  
Author(s):  
Ihab Eldessouki ◽  
Ola Gaber ◽  
Mahmoud A Shehata ◽  
Tariq Namad ◽  
Joseph Atallah ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Growth Factor Receptor ◽  
Papillary Renal Cell Carcinoma ◽  
Type I ◽  
Renal Cell Carcinomas ◽  
Cancer Statistics ◽  
Male Predominance ◽  
Endothelial Growth Factor

The incidence of renal cell carcinomas in adults ranges has been increasing over the past decades in both men and women. Once the incidence was 2.9%, now is reported to have increased to 3%–5% with male predominance according to the most recent reports of cancer statistics. The disease typically describes a group of different histopathological subtypes; the most common is clear cell carcinoma which accounts for 70%–80% of the diagnosed cases, while papillary renal cell carcinoma and chromophobe types represent 20% and 5%, respectively. In 1996, the renal cell carcinomas Heidelberg classification was introduced by Delahunt et al. It divides renal cell tumors into benign and malignant parenchymal neoplasms, excluding Wilm’s tumor and secondary metastases and limiting each subcategory to the most commonly documented genetic abnormalities, if applicable. In this report, we discuss a case of metastatic type I papillary renal cell carcinoma treated with the anti-vascular endothelial growth factor receptor sunitinib and showing marked long-term clinical response. Through this case, we highlight the importance of re-classifying papillary renal cell carcinoma subtypes to prioritize the clinical management of these cases.

scholarly journals PRISM protocol: a randomised phase II trial of nivolumab in combination with alternatively scheduled ipilimumab in first-line treatment of patients with advanced or metastatic renal cell carcinoma

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Hannah L. Buckley ◽  
Fiona J. Collinson ◽  
Gemma Ainsworth ◽  
Heather Poad ◽  
Louise Flanagan ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Phase Iii ◽  
First Line ◽  
Grade 3

Abstract Background The combination of nivolumab, a programmed death-1 (PD-1) targeted monoclonal antibody, with the cytotoxic T-lymphocyte antigen-4 (CTLA-4) targeted antibody, ipilimumab, represents a new standard of care in the first-line setting for patients with intermediate- and poor-risk metastatic renal cell carcinoma (mRCC) based on recent phase III data. Combining ipilimumab with nivolumab increases rates of grade 3 and 4 toxicity compared with nivolumab alone, and the optimal scheduling of these agents when used together remains unknown. The aim of the PRISM study is to assess whether less frequent dosing of ipilimumab (12-weekly versus 3-weekly), in combination with nivolumab, is associated with a favourable toxicity profile without adversely impacting efficacy. Methods The PRISM trial is a UK-based, open label, multi-centre, phase II, randomised controlled trial. The trial population consists of patients with untreated locally advanced or metastatic clear cell RCC, and aims to recruit 189 participants. Participants will be randomised on a 2:1 basis in favour of a modified schedule of 4 doses of 12-weekly ipilimumab versus a standard schedule of 4 doses of 3-weekly ipilimumab, both in combination with standard nivolumab. The proportion of participants experiencing a grade 3 or 4 adverse reaction within 12 months forms the primary endpoint of the study, but with 12-month progression free survival a key secondary endpoint. The incidence of all adverse events, discontinuation rates, overall response rate, duration of response, overall survival rates and health related quality of life will also be analysed as secondary endpoints. In addition, the potential of circulating and tissue-based biomarkers as predictors of therapy response will be explored. Discussion The combination of nivolumab with ipilimumab is active in patients with mRCC. Modifying the frequency of ipilimumab dosing may mitigate toxicity rates and positively impact quality of life without compromising efficacy, a hypothesis being explored in other tumour types such as non-small cell lung cancer. The best way to give this combination to patients with mRCC must be similarly established. Trial registration PRISM is registered with ISRCTN (reference ISRCTN95351638, 19/12/2017). Trial status At the time of submission, PRISM is open to recruitment and data collection is ongoing.

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