Phase II Trial of Bortezomib for Patients With Advanced Renal Cell Carcinoma

2004 ◽  
Vol 22 (18) ◽  
pp. 3720-3725 ◽  
Author(s):  
G. Varuni Kondagunta ◽  
Beverly Drucker ◽  
Lawrence Schwartz ◽  
Jennifer Bacik ◽  
Stephanie Marion ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Partial Response ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Sensory Neuropathy ◽  
Molecular Profile ◽  
Weekly Schedule ◽  
Best Response ◽  
Grade 3 ◽  
Metastatic Rcc

Purpose To assess the efficacy and toxicity of bortezomib (Velcade; Milennium Pharmaceuticals Inc, Cambridge, MA; formerly PS-341) in patients with metastatic renal cell carcinoma (RCC). Patients and Methods Thirty-seven patients with metastatic RCC were treated with bortezomib. The first 25 patients enrolled onto the trial were treated with a dose of 1.5 mg/m2. The dose was decreased to 1.3 mg/m2 for the subsequent 12 patients, because more than 50% of the patients treated at the higher dose required dose reductions. Bortezomib was given by intravenous administration on a twice-weekly schedule for 2 weeks followed by 1 week without treatment until progression or unacceptable toxicity occurred. Twenty-three patients (62%) previously had undergone nephrectomy, and 19 patients (51%) had previously been treated with cytokine therapy. Results Of the 37 assessable patients, the best response was a partial response in four patients (11%; 95% CI, 3% to 25%) and stable disease in 14 patients (38%; 95% CI, 23% to 55%). The four patients with partial response experienced response durations of 8, 8+, 15+, and 20+ months. Grade 2 or 3 sensory neuropathy was present in 10 patients (53%) overall. One patient in the 1.5 mg/m2 group had grade 3 sensory neuropathy; no grade 3 sensory neuropathy was seen in the 1.3 mg/m2 group. Conclusion The results of this trial suggest that bortezomib has an antitumor effect in individual patients with metastatic RCC. The small proportion of patients who achieved a partial response does not support routine use in metastatic RCC. Efforts to identify the molecular profile associated with clinical response or combination therapy with interferon alfa or other novel agents, may be considered.

scholarly journals Antitumor Effect of Cabozantinib in Bone Metastatic Models of Renal Cell Carcinoma

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 781
Author(s):  
Michele Iuliani ◽  
Sonia Simonetti ◽  
Francesco Pantano ◽  
Giulia Ribelli ◽  
Alberto Di Martino ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cell Carcinoma ◽  
Survival Data ◽  
Renal Cell ◽  
Antitumor Effect ◽  
Molecular Profile ◽  
Cell Contact ◽  
Metastatic Rcc

Background: The presence of bone metastases in renal cell carcinoma (RCC) negatively affects patients’ survival. Data from clinical trials has highlighted a significant benefit of cabozantinib in bone metastatic RCC patients. Here, we evaluated the antitumor effect of cabozantinib in coculture models of renal cell carcinoma (RCC) and osteoblasts (OBs) to investigate whether and how its antiproliferative activity is influenced by OBs. Methods: Bone/RCC models were generated, coculturing green fluorescent protein (GFP)-tagged Caki-1 and 786-O cells with human primary OBs in a “cell–cell contact” system. RCC proliferation and the OB molecular profile were evaluated after the cabozantinib treatment. Results: The Caki-1 cell proliferation increased in the presence of OBs (p < 0.0001), while the 786-O cell growth did not change in the coculture with the OBs. The cabozantinib treatment reduced the proliferation of both the Caki-1 (p < 0.0001) and 786-O (p = 0.03) cells cocultured with OBs. Intriguingly, the inhibitory potency of cabozantinib was higher when Caki-1 cells grew in presence of OBs compared to a monoculture (p < 0.001), and this was similar in 786-O cells alone or cocultured with OBs. Moreover, the OB pretreatment with cabozantinib “indirectly” inhibited Caki-1 cell proliferation (p = 0.040) without affecting 786-O cell growth. Finally, we found that cabozantinib was able to modulate the OB gene and molecular profile inhibiting specific proliferative signals that, in turn, could affect RCC cell growth. Conclusions: Overall, the “direct” effect of cabozantinib on OBs “indirectly” increased its antitumor activity in metastatic RCC Caki-1 cells but not in the primary 786-O model.

scholarly journals Immune-Related Meningoencephalitis following Nivolumab in Metastatic Renal Cell Carcinoma

2021 ◽  
pp. 1051-1058
Author(s):  
Lisa B.E. Shields ◽  
Mohammad S. Alsorogi ◽  
Nataliya Mar ◽  
Arash Rezazadeh Kalebasty
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Rare Complication ◽  
Psoas Muscle ◽  
High Dose ◽  
Lower Extremity Weakness ◽  
Left Psoas Muscle ◽  
Metastatic Rcc

While immunotherapy with nivolumab is promising for patients with renal cell carcinoma (RCC), overactivation of the immune system can lead to serious side effects. Immune-related meningoencephalitis without a viral or microbial etiology is a rare complication that may occur in patients treated with checkpoint inhibitors (CPI). Herein, we report a 66-year-old man who underwent a partial nephrectomy which revealed a papillary RCC with clear cell component. Three years later, an abdomen and pelvic CT revealed metastatic lesions in the left psoas muscle and in the left 12th rib. The patient was treated with pazopanib which was discontinued after 2 weeks due to significant hepatic and renal toxicity. He subsequently started sunitinib. Two months later, a chest, abdomen, and pelvic CT demonstrated progressive metastatic RCC in the retroperitoneal mass of the left psoas muscle and paraspinal musculature as well as a left renal mass. The patient was treated with 7 cycles of the CPI nivolumab. He was subsequently hospitalized for 3 weeks after experiencing bilateral lower extremity weakness, lethargy, several falls, hyperthermia, confusion, and gait abnormalities. A CSF analysis demonstrated a lymphocyte pleocytosis with elevated protein and no bacterial or viral growth. The patient was treated with high-dose steroids after which his symptoms resolved. Chest, abdomen, and pelvic CT scans over the next 3 years revealed no evidence of metastatic disease, reflecting a progression-free survival of 40 months. We highlight the unique case of a patient with metastatic RCC who experienced immune-related meningoencephalitis following immunotherapy with nivolumab. Medical oncologists should be alert to the potential development of immune-related encephalitis in patients treated with nivolumab and should promptly diagnose and treat this concerning condition. The excellent oncologic outcome of this case emphasizes the need for continued aggressive measures for management of CNS toxicity resulting from CPI therapy.

scholarly journals Individual approach in choosing second-line targeted therapy for metastatic renal cell carcinoma

2018 ◽  
Vol 14 (2) ◽  
pp. 68-78 ◽  
Author(s):  
B. Ya. Alekseev ◽  
I. M. Shevchuk ◽  
A. D. Kaprin
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Surgical Treatment ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Optimal Dosage ◽  
Second Line ◽  
Newly Diagnosed ◽  
Disease Prognosis ◽  
Metastatic Rcc

Renal cell carcinoma (RCC) is one of the most common genitourinary malignancies worldwide. Approximately 25–30 % of newly diagnosed patients have metastatic RCC (mRCC), whereas in 20–30 % of cases, dissemination occurs after radical surgical treatment. The development of targeted and immunooncological agents in recent years significantly increased survival in patients with mRCC. However, clinicians faced a problem of choosing an optimal therapeutic regimen to achieve maximum effectiveness of the treatment. This article discusses the choice of second-line drugs for mRCC, advantages of axitinib and its optimal dosage, and efficacy of sunitinib depending on the disease prognosis.

Interleukin-4 Promoter Polymorphisms: A Genetic Prognostic Factor for Survival in Metastatic Renal Cell Carcinoma

2007 ◽  
Vol 25 (7) ◽  
pp. 845-851 ◽  
Author(s):  
Thomas Kleinrath ◽  
Christoph Gassner ◽  
Peter Lackner ◽  
Martin Thurnher ◽  
Reinhold Ramoner
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clinical Course ◽  
Prognostic Significance ◽  
Interleukin 4 ◽  
Promoter Polymorphisms ◽  
Cox Regression Analysis ◽  
Metastatic Rcc

Purpose Renal cell carcinoma (RCC) is considered a cytokine-responsive tumor. The clinical course of a patient may thus be influenced by the patient's capacity to produce distinct cytokines. Therefore, cytokine gene polymorphisms in RCC patients were analyzed to determine haplotype combinations with prognostic significance. Patients and Methods A selection of 21 single nucleotide polymorphisms within the promoter regions of 13 cytokine genes were analyzed in a cross-sectional single-center study of 80 metastatic RCC patients. Univariate and multivariate analyses and the Cox forward-stepwise regression model were chosen to assess genetic risk factors. Results Multivariate Cox regression analysis confirmed by a bootstrap technique identified the heterozygous IL4 genotype −589T−33T/−589C−33C as an independent prognostic risk factor (risk ratio, 3.1; P < .01; 95% CI, 1.4 to 6.9; adjusted for age, sex, and nuclear grading) in metastatic RCC patients. IL4 haplotype −589T−33T and −589C−33C were found with a frequency of 0.069 and 0.925, respectively, which represents a two-fold decrease of IL4 haplotype −589T−33T (P < .01) and an increase of IL4 haplotype −589C−33C frequency (P < .05) in metastatic RCC compared with other white reference study populations. The median overall survival was decreased 3.5-fold (P < .05) in heterozygote patients carrying IL4 haplotype −589T−33T and −589C−33C (3.78 months) compared with patients homozygote for IL4 haplotype −589C−33C (13.44 months). In addition, a linkage disequilibrium between the IL4 gene and the KIF3A gene was detected. Conclusion Our findings indicate that IL4 promoter variants influence prognosis in patients with metastatic RCC and suggest that genetically determined interleukin-4 (IL-4) production affects the clinical course of the disease possibly through regulation of immune surveillance.

scholarly journals Unusual presentation of renal cell carcinoma: A rare case report

2018 ◽  
Vol 10 (02) ◽  
pp. 241-244 ◽  
Author(s):  
Manjari Kishore ◽  
Devender Singh Chauhan ◽  
Shruti Dogra
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Upper Lip ◽  
Rare Case Report ◽  
Aggressive Tumor ◽  
Oral Tumors ◽  
Metastatic Rcc

AbstractCutaneous and intraoral metastasis from any malignancy is not common. Cutaneous spread is usually noted in 5%–10% of high-grade malignancies, as in carcinoma breast, lung, colon, ovary, and malignant melanoma. Only 4.6% cases of cutaneous spread are from renal cell carcinoma (RCC). Intraoral spread from RCC is much rarer with an incidence of approximately 1% of all malignant oral tumors, noted sometimes in tongue, palate, buccal mucosa, gingiva, and lips. RCC is a highly aggressive tumor which requires early diagnosis for increasing the chance of cure. In our case, a 54-year-old male presented with swelling over upper lip, scalp, and retromolar area, which on histopathology and immunohistochemistry revealed clear cell carcinoma compatible with metastatic RCC.

scholarly journals Exceptional Response of Metastatic Chromophobe Renal Cell Carcinoma to Vascular Endothelial Growth Factor (VEGF) Inhibitors: Should Increased VEGF-C Expression Be Used to Guide Treatment?

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Jacob W. Bruinius ◽  
Karl J. Dykema ◽  
Sabrina L. Noyes ◽  
Bin Tean Teh ◽  
Brian R. Lane
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Clear Cell ◽  
Locally Advanced ◽  
Chromophobe Renal Cell Carcinoma ◽  
Molecular Profile ◽  
Vegf Inhibitors ◽  
Cell Renal Cell Carcinoma

There is sparse literature demonstrating effective treatments for metastatic chromophobe renal cell carcinoma (ChRCC). The tyrosine kinase inhibitor (TKI) sunitinib selectively inhibits the VEGF pathway and it is a standard care for metastatic clear cell renal cell carcinoma (ccRCC), although data supporting its use in ChRCC is much more limited. A 56-year-old underwent palliative nephrectomy for locally-advanced ChRCC with sarcomatoid differentiation. Tumor gene expression profiling using Affymetrix HG-U133 Plus 2.0 GeneChip platform demonstrated significantly elevated VEGF-C expression compared to normal renal tissue n=12 and other types RCC n=158. Adjuvant sunitinib was used to treat his residual unresectable retroperitoneal lymph nodes. He demonstrated an exceptional response and underwent complete surgical resection four months later. He has been managed with TKIs for nearly nine years with only minimal disease progression. Additional studies exploring treatment options for patients with non-clear cell RCC are needed; in their absence, we would recommend TKIs for patients whose tumors bear a similar molecular profile.

scholarly journals Determinants of treatment in patients with stage IV renal cell carcinoma

BMC Urology ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Christopher S. Hollenbeak ◽  
Eric W. Schaefer ◽  
Justin Doan ◽  
Jay D. Raman
Keyword(s):  
Renal Cell Carcinoma ◽  
Elderly Patients ◽  
Cell Carcinoma ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Stage Iv ◽  
Data Set ◽  
Causes Of Mortality ◽  
Competing Causes ◽  
Metastatic Rcc

Abstract Background Advances in systemic targeted therapies afford treatment opportunities in patients with metastatic renal cell carcinoma (RCC). Elderly patients with metastatic RCC present a subpopulation for consideration owing to competing causes of mortality and benefits seen with new therapeutic agents. We investigate treatment patterns for elderly patients with stage IV RCC and determine factors associated with not receiving treatment. Methods The Surveillance Epidemiology and End Results (SEER) Medicare linked data set contained 949 stage IV RCC patients over age 65 diagnosed between 2007 and 2011. Treatment approach was modeled using multinomial logistic regression. Landmark analysis at 6 months accounted for early death as a potential explanation for no treatment. Results Of the 949 patients with stage IV RCC, 26.2% received surgery and 34.1% received systemic therapy within 6 months of diagnosis. Among our entire cohort, over half (51.2%) had no evidence of receiving surgery or systemic therapy. Among the 447 patients who survived at least 6 months, 26.6% did not receive treatment during this time. Older patients and those with a higher Charlson Comorbidity Index (CCI) had lower odds of being treated with surgery, systemic therapy, or both. Conversely, married patients had higher odds of receiving these therapies. These associations were largely sustained in the 6-month landmark analyses. Conclusions Elderly patients with metastatic RCC present a unique subpopulation for consideration owing to competing causes of mortality. Many elderly patients with stage IV RCC did not receive surgery or systemic therapy up to 6 months from diagnosis. Several clinical and demographic factors were associated with this observation. Further investigation is needed to understand the rationale underlying the underutilization of systemic therapy in elderly patients.

Understanding the adverse event experience in the S-TRAC adjuvant trial of sunitinib for high-risk renal cell carcinoma

2020 ◽  
Vol 16 (4) ◽  
pp. 39-47
Author(s):  
Sarah Yenser Wood ◽  
Joanne C Ryan ◽  
Andrew G Clair ◽  
Daniel J George
Keyword(s):  
Renal Cell Carcinoma ◽  
Adverse Event ◽  
High Risk ◽  
Cell Carcinoma ◽  
Adjuvant Treatment ◽  
Renal Cell ◽  
Disease Recurrence ◽  
Event Management ◽  
The Usa ◽  
Metastatic Rcc

Until recently, the sole treatment for patients with nonmetastatic renal cell carcinoma (RCC) was nephrectomy followed by observation. As metastatic RCC (mRCC) remains largely incurable (5-year survival rate ∼12%), adjuvant treatment, with potential to prevent/delay disease recurrence, is needed. In November 2017, sunitinib was approved in the USA as the first adjuvant therapy for patients at high risk for recurrent RCC postnephrectomy based on results from the S-TRAC trial. Patients eligible for adjuvant treatment have no evidence of disease and may be less willing to tolerate side effects. Therefore, proactive adverse event management is critical for keeping patients on adjuvant treatment and requires understanding the subtle differences in the adverse event profile of sunitinib in the adjuvant versus metastatic RCC setting.

Medical Treatment of Metastatic Renal Cell Carcinoma

1980 ◽  
Vol 66 (2) ◽  
pp. 235-240 ◽  
Author(s):  
Umberto Tirelli ◽  
Sergio Frustaci ◽  
Enzo Galligioni ◽  
Andrea Veronesi ◽  
Mauro G. Trovò ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Medical Treatment ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Medical Oncology ◽  
Primary Treatment ◽  
Duration Of Response ◽  
Treatment Agent ◽  
Metastatic Rcc

Thirty five patients with metastatic RCC were observed over a 57 months period in our Division of Radiotherapy and Medical Oncology, and 30 are evaluable for this analysis. MPA was selected as primary treatment agent in 23 patients, VLB singly, in combination with MPA or in combination with CCNU was used in 1.4 and 2 patients. With MPA the TR rate was 3/23 (1 CR and 2 PR). Duration of response for the patient with CR was 6 months whereas for the patients with PR was 21 and 14 months respectively. 4 additional patients showed NC. With VLB-MPA the TR rate was 1/4 (1 PR). Duration of PR was 3 months. The median duration of survival for the 11 patients with CR, PR and NC was 14 months whereas for the 19 patients with NR was 7 months (p < 0.01). TES and TAM showed no or minimal activity as second treatment agents.

Phase I Trial of 40-kd Branched Pegylated Interferon Alfa-2a for Patients With Advanced Renal Cell Carcinoma

2001 ◽  
Vol 19 (5) ◽  
pp. 1312-1319 ◽  
Author(s):  
Robert J. Motzer ◽  
Ashok Rakhit ◽  
Michelle Ginsberg ◽  
Karen Rittweger ◽  
Jacqueline Vuky ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Serum Concentration ◽  
Phase I ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Subcutaneous Administration ◽  
Interferon Alfa ◽  
Advanced Renal Cell Carcinoma ◽  
Grade 3 ◽  
Dose Limiting Toxicity

PURPOSE: Pegylated (40 kd) interferon alfa-2a (IFNα2a) (PEGASYS, Hoffman-La Roche, Nutley, NJ; PEG-IFN) is a modified form of recombinant human IFNα2a with sustained absorption and prolonged half-life after subcutaneous administration. A phase I study of PEG-IFN with pharmacokinetic and pharmacodynamic evaluations was conducted in previously untreated patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS: Twenty-seven patients were enrolled onto cohorts of three or six patients. PEG-IFN was administered on a weekly basis by subcutaneous injection. The dose was escalated from 180 μg/wk to a maximum of 540 μg/wk in 90-μg increments. Serial venous blood samples were drawn to assess concentrations of PEG-IFN and two immunologic surrogates, neopterin and 2′-5′ oligoadenylate synthetase (OAS). RESULTS: The maximum-tolerated dose was determined as 540 μg/wk, because two patients experienced dose-limiting toxicity within 28 days of starting treatment. One developed serum grade 3 ALT elevation, and a second developed grade 3 fatigue. Six patients were treated at 450 μg/wk without dose-limiting toxicity. Over the course of treatment, the side-effect profile was mostly mild to moderate in intensity. Adverse events included fatigue, fever, headache, myalgia, nausea, and decreased appetite. Five patients (19%) achieved a partial response. The mean maximum serum concentration increased from 5.0 to 27 ng/mL, and mean area under the curve increased from 247 to 2,981 ng/h/mL, with dose escalation from 180 μg/wk to 540 μg/wk. Serum concentration of PEG-IFN was sustained at close to peak during the dosing interval, and steady-state was achieved in approximately 5 weeks. The immunologic surrogates, neopterin and OAS, were induced at all doses with a sustained concentration profile similar to PEG-IFN. CONCLUSION: PEG-IFN is a modified form of IFNα2a with distinct pharmacokinetic advantages and immunomodulatory and antitumor activity for patients with advanced RCC. A dose of 450 μg/wk by subcutaneous administration was determined as a suitable dose for further study. PEG-IFN is more convenient to administer than IFNα and has potential for increased efficacy, less toxicity, or both. The efficacy and toxicity of PEG-IFN will be further assessed in clinical trials and compared with IFNα.

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