Although significant progress has been made for metastatic renal cell carcinoma (MRCC), very little progress has been achieved for non-clear cell MRCC. Thus, we performed a phase II, multicenter ...trial of capecitabine in patients with non-clear cell MRCC.
Adult patients with MRCC containing <50% of clear cells were eligible. All patients received oral capecitabine (1,250 mg/m) twice daily for 14 days, followed by 14 days of rest. Primary end point was objective response rate. On the basis of Chen and Ng 2-stage accrual design, maximum planned enrollment was 51 patients. This study is registered with ClinicalTrials.gov, NCT01182142.
Fifty-one patients enrolled between February 2006 and January 2009. Most patients were men (72.5%), who had papillary RCC (76.5%), Memorial Sloan Kettering Cancer Center intermediate prognosis (86%), and had not been treated earlier (92%). The objective response rate was 26%. Two patients (4%) had a complete response. Stable disease was achieved in 24 (47%) patients. The median progression-free survival was 10.1 months 95% confidence interval (CI), 8.7-11.5, and overall survival was 18.3 months (95% CI, 15.5-21.1). The 1-year overall survival was 71% (95% CI, 63%-79%). Major grades 3 to 4, treatment-related toxicities included diarrhea (2%), esophageal mucosal inflammation (2%), hand-foot syndrome (4%), thrombocytopenia (9.8%), and neutropenia (8%). No patients were withdrawn because of laboratory abnormalities.
Capecitabine has clinical activity in MRCC patients who have non-clear cell histology and a good or intermediate prognosis. Additional prospective randomized trial comparing capecitabine with placebo is required.
Everolimus is an orally administered inhibitor of the mammalian target of rapamycin (mTOR) recommended for patients with metastatic renal cell carcinoma (mRCC) who progressed on previous vascular ...endothelial growth factor (VEGF) receptor-tyrosine kinase inhibitor therapy. Efficacy of everolimus in patients who progressed on anti-VEGF monoclonal antibody bevacizumab is unknown. We did a multicenter prospective trial of everolimus in patients with mRCC whose disease had progressed on bevacizumab ± interferon alpha (IFN). Patients with clear-cell mRCC which had progressed on bevacizumab ± IFN received everolimus 10 mg once daily. The primary end point was the proportion of patients remaining progression-free for 56 days, and a two-stage Simon design was used, with 80 % power and an alpha risk of 5 %. This study is registered with ClinicalTrials.gov, number NCT02056587. From December 2011 to October 2013, a total of 37 patients (28 M, 9 F) were enrolled. Median age was 60.5 years (range 41–66), 11 % had Eastern Cooperative Oncology Group Performance Status (ECOG PS) >2, and Memorial Sloan-Kettering Cancer Center (MSKCC) favorable/intermediate risk was 38/62 %. Five (14 %) patients had a confirmed partial response and 26 (70 %) patients had a stable disease. Median progression-free survival was 11.5 months (95 % CI, 8.8–14.2). Median overall survival was not reached. No grade 3 or 4 treatment-related toxicities were observed. The most common grade 2 adverse events were fatigue (19 %) and pneumonitis (8 %). Everolimus demonstrated a favorable toxicity profile and promising anti-tumor activity as a second-line therapy in metastatic renal cell carcinoma (RCC) patients previously treated with bevacizumab ± IFN.
Background
Targeted therapy with axitinib resulted in a greater objective response rate and prolonged progression-free survival (PFS) compared to sorafenib in patients with previously treated ...metastatic renal cell carcinoma (mRCC) in the phase 3 AXIS study, where 75% of patients had intermediate and poor International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk.
Objective
In this phase 2 study (FavorAx), we assessed the activity of axitinib in mRCC patients with a favorable risk and history of prior vascular endothelial growth factor receptor (VEGFR)-directed therapy.
Patients and Methods
Patients were required to have clear-cell mRCC, favorable risk according to IMDC criteria, and to have received first-line treatment with sunitinib or pazopanib. Prior treatment with other agents was not permitted. The primary endpoint of the study was 5 months PFS. Additional endpoints included response rate, safety, PFS, and overall survival (OS).
Results
A total of 21 patients were enrolled, 62% of whom were male. The mean age was 60 years. Eleven (52%) patients had two or more metastatic sites. 67% and 33% of patients received first-line sunitinib or pazopanib, respectively, with a median PFS of 17 months 95% confidence interval (CI), 14–20. After a median follow-up of 25 months, the median PFS was 19 months (95% CI, 15–23). The current study did achieve its primary endpoint based on the 5-month PFS of 100%. The median OS was not yet reached. The 18 months OS rate was 85.7%. The objective response rate was 33% and one patient achieved a complete response. Seven patients had dose escalation of axitinib and four patients had dose reduction. Grade 3 adverse events were observed in 19% of cases. There was no discontinuation of therapy due to toxicity.
Conclusions
The encouraging PFS and favorable safety profile observed in the FavorAx study support the administration of axitinib in mRCC patients with favorable IMDC risk and a history of prior sunitinib or pazopanib.
Von Hippel-Lindau disease (VHL) is a major heritable renal cell cancer (RCC) syndrome. 24-45% of VHL patients have a cumulative risk to develop RCC. The management of VHL has changed significantly as ...clinicians have learned how to best balance the risk of cancer dissemination while minimizing renal morbidity. Despite the improving management of this disease, there are no evidence-based guidelines of the treatment of localized and advanced RCC in VHL. Here, we describe a 39-year-old patient with VHL disease who developed metastatic RCC and received sunitinib with complete remission.
The overall survival (OS) results in patients with
-positive metastatic non-small-cell lung cancer (NSCLC) have rarely been reported. The aim of this prospective-retrospective cohort study was to ...obtain real-world data on the use of crizotinib or chemotherapy in patients with
-positive metastatic NSCLC in Russia.
Patients with epidermal growth factor receptor-negative metastatic NSCLC were screened in 23 cancer centers. To be eligible, patients were required to have confirmation of
rearrangement. Patients were treated with crizotinib (250 mg twice daily; n = 96) or the investigator's choice of platinum-based chemotherapy (n = 53). The primary end point was OS.
A total of 149
-positive patients were included. Mean age was 53 years in both groups. Patients were predominately women (59%) and never-smokers (74%), and most patients had adenocarcinoma histology (95%). At a median follow-up time of 15 months, 79 of the 149 patients included in the analysis had died. Median OS from the start of treatment was 31 months (95% CI, 28.5 to 33.5 months) in the crizotinib group and 15.0 months (95% CI, 9.0 to 21.0 months) in the chemotherapy group (
< .001). The objective response rate was 34% in the crizotinib group. Among patients with brain metastasis, one complete response (6%) and five partial responses (31%) were achieved. Grade 3 adverse events were observed in three patients (3%) in the crizotinib group.
The improved OS observed in crizotinib clinical trials in
-positive NSCLC was also observed in the less selective patient populations treated in daily practice in Russia. The use of standard chemotherapy in these patients remains common but seems inappropriate as a result of the effectiveness of newer treatments, such as crizotinib.
Abstract
Objective. Fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) has recently emerged as a critical event in the transformation and tumorigenicity of several murine and human ...tumors. This pathway could be a mechanism driving angiogenesis in patients with metastatic renal cell carcinoma (RCC). Membrane antigens such as FGFR expressed in RCC are attractive targets for new therapeutic and diagnostic applications. This study evaluated the expression of FGFR1 and FGFR2 in RCC. Material and methods. Formalin-fixed, paraffin-embedded specimens of 100 primary tumors and 40 metastatic lymph nodes removed from 140 untreated RCC patients were evaluated by immunohistochemistry with FGFR1 and FGFR2 antibodies. The extent of FGFR expression was compared with 40 specimens of normal human kidney tissue (selected from the surgical diagnostic files). Significant differences in the immunoexpression of FGFR among these groups were assessed bychi-squared and Fisher's exact tests using a semi-quantitative scoring system on the extent of stained cells and intensity of corresponding immunostained cells (0 to 3+). Results. Expression of FGFR1 was observed in 98% (98/100) of primary renal tumors and in 82.5% (33/40) of lymph-node metastases. Intensity was 3+ in allcases. Nuclear expression of FGFR1 was found in 68% (95/140). FGFR2 staining was seen in 4% (4/100) of primary tumors and in 5% (2/40) of lymph-node metastases. FGFR2 was expressed in RCC of non-clear cell histology. FGFR1 expression was significantly lower in the normal kidney tissue(p = 0.001) and was detected in 2.5% of cases (1/40); no FGFR2 expression was found. Conclusion. This study has shown for the first time that FGFR1 is highly expressed in RCC patients.
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