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Metastatic RCC (metastatic + rcc)
Selected AbstractsMetastatic Renal Cell Carcinoma to the Head and Neck,THE LARYNGOSCOPE, Issue 9 2002Keith M. Pritchyk MD Abstract Objectives The objectives of the study were to present four cases of renal cell carcinoma (RCC) metastatic to the head and neck, to recognize the appearance on radiographic studies, to understand the importance of preoperative embolization, and to review the results of treatment. Study Design Retrospective review of patients diagnosed with metastatic RCC to the head and neck. Methods The records of four patients diagnosed with metastatic RCC at a tertiary medical center over a 5-year period from 1996 to 2001 were reviewed and analyzed for demographic and outcomes data. Results Metastatic RCC to the head and neck was seen in the following locations: nasal cavity, lower lip, hard palate, tongue, and maxillary sinus. Presenting signs were loose upper molars, dysphagia, nasal obstruction, lower lip lesion, recurrent epistaxis, and foul nasal drainage. Histological studies confirmed metastasis of RCC in all four patients. Treatment consisted of preoperative radiation therapy, embolization, and local excision with adjunct chemotherapy. Conclusions Metastatic RCC to the head and neck is rare but can have serious consequences if not recognized before biopsy. We present several treatment options with local excision as the primary mode of treatment. [source] Resection of renal metastases to the pancreas: a surgical challengeHPB, Issue 3 2003D Zacharoulis Background Metastasis to the pancreas from renal cell carcinoma (RCC) is distinctly uncommon. Most cases are detected at an advanced stage of the disease and are thus unsuitable for resection. A solitary RCC metastasis to the head of pancreas is rarely encountered and, although it is potentially amenable to surgical resection, surgeons may be hesitant to perform pancreatoduodenectomy. Cases outlines Two patients with a solitary RCC metastasis to the head of pancreas were treated by pancreatoduodenectomy, while a third with multiple RCC metastases declined any treatment. Two of the patients were asymptomatic, and one presented with anaemia and mild abdominal pain. Computed tomography (CT) and angiography were used to exclude other metastases and to assess resectability of the pancreatic tumour. All three patients are still alive, those with resectable disease at 2 years and 9 years and the one with irresectable disease at 4 years. Discussion Isolated RCC metastasis to the pancreas is a rare event. Patients present either on follow-up imaging or with symptoms such as mild abdominal pain, weight loss, jaundice, anaemia or gastrointestinal bleeding (whether occult or overt). Dynamic spiral CT can visualise the tumour and exclude distant metastasis. Angiography often reveals a highly vascularised tumour and will help to assess resectability. In the absence of widespread disease, pancreatic resection can provide long-term survival in metastatic RCC, although few cases have been reported with lengthy follow-up. The prognosis is better than for pancreatic adenocarcinoma. [source] Immunotherapy against metastatic renal cell carcinoma with mature dendritic cellsINTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2007Akihiko Matsumoto Objective: We performed a clinical trial of immunotherapy using autologous mature dendritic cells (DC) pulsed with autologous tumor lysate, for patients with metastatic renal cell carcinoma (RCC). Methods: Patients with refractory metastatic RCC were enrolled in the study. All of them received interferon (IFN)-, treatment after nephrectomy and were followed over 3 months prior to this study. Autologous monocyte-derived immature DC were pulsed with lysate from autologous primary tumor as the antigen and keyhole limpet hemocyanin (KLH) as immunomodulator, and cultured in the presence of tumor necrosis factor (TNF)-,, interleukin (IL)-1,, and prostaglandin (PG)E2 to generate mature DC. Mature DC were injected intradermally near bilateral inguinal lymph nodes of the patients. A delayed-type hypersensitivity (DTH) test and enzyme-linked immunospot (ELISPOT) assay were performed to evaluate the immunological response. After 4 months from first injection, the clinical effect was evaluated by diagnostic imaging. Results: The treatments were well tolerated without significant toxicity by the patients who were an average of 65.7 years old and had multiple metastases in the lung and other organs. One of the two patients developed a positive DTH reaction to tumor lysate and the other patient only to KLH. The patient with a positive DTH reaction to tumor lysate had stable disease in the clinical evaluation. Conclusions: We confirmed the safety of DC therapy in this clinical trial. The DTH test revealed that the DC therapy induced immunological response to RCC. On the other hand, it was necessary to reconsider the patient selection criteria. [source] Neopterin in renal cell carcinoma: inhalational administration of interleukin-2 is not accompanied by a rise of urinary neopterinLUMINESCENCE: THE JOURNAL OF BIOLOGICAL AND CHEMICAL LUMINESCENCE, Issue 4-5 2005Bohuslav Melichar Abstract Inhalational administration of interleukin-2 (IL-2) is effective in controlling renal cell carcinoma (RCC) lung metastases with minimal toxicity. Neopterin is an indicator of systemic immune activation in metastatic cancer and is increased after systemic IL-2 administration. Urinary neopterin was investigated in 13 patients with metastatic RCC and 18 controls. In seven patients, urinary neopterin was followed before and after treatment with inhalational IL-2. Neopterin was measured by highperformance liquid chromatography and creatinine was determined by Jaffé reaction. Urinary neopterin was significantly increased in patients with metastatic RCC compared to controls (257 ± 263 µmol/mol creatinine vs. 110 ± 41 µmol/mol creatinine; Mann,Whitney U-test, p < 0.05). Median survival was significantly longer in patients with urinary neopterin <173 µmol/mol creatinine compared to patients with neopterin ,173 µmol/mol creatinine (698 vs. 245 days; log-rank test, p < 0.05). No significant increase was observed after inhalational IL-2 therapy (147 ± 101 vs. 153 ± 54 µmol/mol creatinine). We conclude that urinary neopterin is increased in patients with metastatic RCC, and higher neopterin concentrations are indicative of poor prognosis. The absence of an increase in urinary neopterin after inhalational IL-2 therapy is in accord with the lack of significant systemic toxicity. Copyright © 2005 John Wiley & Sons, Ltd. [source] Contribution of the Src family of kinases to the appearance of malignant phenotypes in renal cancer cellsMOLECULAR CARCINOGENESIS, Issue 4 2005Yuko Yonezawa Abstract Although the constitute activation of the Src family of kinases (Src) has been established as a poor prognostic factor in several types of cancer, the role of Src in renal cell carcinoma (RCC) has not been defined. This study aimed to determine whether Src could contribute to the appearance of malignant phenotypes in RCC. The role of Src in the appearance of malignant phenotypes in RCC was examined in two human renal cancer cell lines, Caki-1 from human metastatic RCC and ACHN from human primary RCC. Src activity in Caki-1 cells was higher than that in ACHN cells, and this difference corresponded to the difference of PP1 (a Src family inhibitor)-induced cytotoxicity on the two cells. The difference in cytotoxicity between the cells did not depend on cell cycle regulation but on the induction of apoptosis, and the difference in apoptosis particularly related to the reduction of the Bcl-xL level. Furthermore, in Caki-1 cells with higher Src activity, Src stimulated the production of vascular endothelial growth factor (VEGF), partially via the activation of Stat3, and the inhibition of Src activity caused a reduction of the VEGF level in serum, angiogenesis, and tumor development in a xenograft model. These results suggested that Src contributed to the appearance of malignant phenotypes in renal cancer cells, particularly due to the resistance against apoptosis by Bcl-xL and angiogenesis stimulated by Src-Stat3-VEGF signaling. © 2005 Wiley-Liss, Inc. [source] Photosensitizing and Radiosensitizing Effects of Hypericin on Human Renal Carcinoma Cells in VitroPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2008Johannes Theodor Wessels The renal cell carcinoma (RCC) is extremely resistant to chemotherapy and radiotherapy. The prognosis of patients with metastatic RCC still remains poor, the median survival is less than 12 months. Therefore, new therapeutic options are desirable. The aim of this study was to investigate the photosensitizing and radiosensitizing effects of hypericin on human RCC cells in vitro. First the RCC-derived cell lines A498 and ACHN were incubated with different concentrations of hypericin. In vitro uptake and intracellular distribution of hypericin were confirmed by fluorescence microscopy. Subsequently cells were illuminated and irradiated with a dose of 2,8 Gy, respectively. Finally, metabolic activity, apoptosis and clonogenic survival were investigated. Uptake of hypericin was observed for almost all cells. Hypericin treatment combined with illumination led to a 94,97% decrease in metabolic activity and caused apoptosis in nearly 100% of RCC cells. Hypericin enhanced the radiosensitivity of A498 cells in vitro. The clonogenic survival after irradiation was significantly reduced by hypericin treatment. Taken together, the photosensitizing and radiosensitizing effects of hypericin on human RCC cells we found in this investigation could be of clinical relevance, e.g. for radiotherapy and intraoperative photodynamic therapy, respectively. [source] Metastatic Renal Cell Carcinoma to the Head and Neck,THE LARYNGOSCOPE, Issue 9 2002Keith M. Pritchyk MD Abstract Objectives The objectives of the study were to present four cases of renal cell carcinoma (RCC) metastatic to the head and neck, to recognize the appearance on radiographic studies, to understand the importance of preoperative embolization, and to review the results of treatment. Study Design Retrospective review of patients diagnosed with metastatic RCC to the head and neck. Methods The records of four patients diagnosed with metastatic RCC at a tertiary medical center over a 5-year period from 1996 to 2001 were reviewed and analyzed for demographic and outcomes data. Results Metastatic RCC to the head and neck was seen in the following locations: nasal cavity, lower lip, hard palate, tongue, and maxillary sinus. Presenting signs were loose upper molars, dysphagia, nasal obstruction, lower lip lesion, recurrent epistaxis, and foul nasal drainage. Histological studies confirmed metastasis of RCC in all four patients. Treatment consisted of preoperative radiation therapy, embolization, and local excision with adjunct chemotherapy. Conclusions Metastatic RCC to the head and neck is rare but can have serious consequences if not recognized before biopsy. We present several treatment options with local excision as the primary mode of treatment. [source] High-dose interleukin-2 immunotherapy is safe for patients with metastatic renal cell carcinoma on dialysisBJU INTERNATIONAL, Issue 2 2006JOHN P. BRUSKY OBJECTIVE To report our experience of high-dose interleukin-2 immunotherapy for patients with metastatic renal cell carcinoma (RCC) on haemodialysis. PATIENTS AND METHODS Two anephric patients with metastatic RCC on haemodialysis received interleukin-2 (600 000 IU/kg) every 8 h for a maximum of 14 doses. The patients rested for 9 days and cycles were repeated as tolerated. A nephrologist followed the patients during treatment and they received nearly daily haemodialysis. RESULTS These two cases were treated with high-dose interleukin-2 and had no unusual toxicity or adverse events. The first patient tolerated five, five, four, four and one dose of interleukin-2 over five cycles. He had a partial response to treatment with a decrease in size of a mediastinal mass, but ultimately developed progressive disease and died 32 months later. The second patient had four cycles of interleukin-2 (13, 13, 14 and nine doses). He initially maintained stable disease throughout treatment, but the disease ultimately progressed and he died 19 months later. CONCLUSIONS We recommend considering high-dose interleukin-2 immunotherapy in highly selected dialysis patients with metastatic RCC. Further study is required to determine the safety, efficacy and optimum dosing in this group. [source] A lower dose of thalidomide is better than a high dose in metastatic renal cell carcinomaBJU INTERNATIONAL, Issue 4 2005Sandy Srinivas OBJECTIVE To conduct a dose-finding trial using a single low dose and dose escalation of a higher dose of thalidomide in patients with metastatic renal cell carcinoma (RCC), and to evaluate the antineoplastic effectiveness of thalidomide as an anti-angiogenic agent on RCC. PATIENTS AND METHODS The 14 patients enrolled in the study had progressive measurable metastatic RCC and consented to participate. Patients were randomized to either a fixed low dose of 200 mg of thalidomide or to a high dose of 800 mg that was increased to a maximum dose of 1200 mg daily. Patients were evaluated for response after 8 weeks of therapy. RESULTS Stable disease was achieved in six patients and was seen in both the low-dose and high-dose thalidomide groups. The median overall survival was 9 months. The low-dose thalidomide regimen was better tolerated and patients survived longer than those on the high-dose regimen (16 vs 6 months, P = 0.04) CONCLUSION The use of low-dose thalidomide in patients with metastatic RCC was well tolerated and they survived for longer than those on the high-dose regimen. [source] Sunitinib-induced macrocytosis in patients with metastatic renal cell carcinomaCANCER, Issue 6 2008Brian I. Rini MD Abstract BACKGROUND. Sunitinib and sorafenib are small molecules that inhibit the vascular endothelial growth factor and related receptors with substantial clinical activity reported in metastatic renal cell carcinoma (RCC). Cytopenia and macrocytosis have been described in patients treated with these agents. METHODS. A retrospective review of all patients with metastatic RCC who were treated with sunitinib or sorafenib for at least 3 months at the Cleveland Clinic Taussig Cancer Institute was undertaken. Complete blood count (CBC) data including red blood cell indices were recorded at baseline, after 3 months of therapy, and at the end of treatment. RESULTS. A total of 61 patients were treated with sunitinib and 37 patients were treated with sorafenib with available CBC data. In patients treated with sunitinib, the median corpuscular volume (MCV) increased significantly at 3 months compared with baseline (median increase of 5.1 femtoliters [fL]; P < .001) and continued to increase throughout treatment. Patients who developed hypothyroidism had a larger MCV increase at 3 months than patients who remained euthyroid (P = .06), although macrocytosis was observed in patients without hypothyroidism. Ten patients discontinued sunitinib therapy, and the MCV decreased in all patients within 2 to 4 months, without further intervention. Bone marrow analysis of 4 patients revealed a hypocellular bone marrow with trilineage hematopoiesis and no evidence of metastasis. There was no evidence of folate or vitamin B12 deficiency. In contrast to sunitinib, there was no change in the MCV for patients treated with sorafenib. CONCLUSIONS. Macrocytosis was a common occurrence after treatment with sunitinib but not sorafenib in patients with metastatic RCC. Sunitinib-induced macrocytosis is reversible with drug discontinuation. Cancer 2008. © 2008 American Cancer Society. [source] Phase II study of lenalidomide in patients with metastatic renal cell carcinomaCANCER, Issue 11 2006Toni K. Choueiri MD Abstract BACKGROUND. Lenalidomide (LEN) is a structural and functional analogue of thalidomide that has demonstrated enhanced immunomodulatory properties and a more favorable toxicity profile. A Phase II, open-label study of LEN in patients with metastatic renal cell carcinoma (RCC) was conducted to determine its safety and clinical activity. METHODS. Patients with metastatic RCC received LEN orally at a dose of 25 mg daily for the first 21 days of a 28-day cycle. The primary endpoint was the objective response rate. Time to treatment failure, safety, and survival were secondary endpoints. RESULTS. In total, 28 patients participated in the trial and were included in the current analysis. Three of 28 patients (11%) demonstrated partial responses and continued to be progression-free for >15 months. Eleven patients (39%) had stable disease that lasted >3 months, including 8 patients who had tumor shrinkage. In total, 6 patients (21%) remained on the trial, and 5 additional patients continued to be followed for survival. The median follow-up for those 11 patients was 13.5 months (range, 8.3,17.0 months). The median survival had not been reached at the time of the current report. Serious adverse events included fatigue (11%), skin toxicity (11%), and neutropenia (36%). CONCLUSIONS. LEN demonstrated an antitumor effect in metastatic RCC, as evidenced by durable partial responses. LEN toxicities were manageable. Further studies will be required to assess the overall activity of LEN in patients with metastatic RCC. Cancer 2006. © 2006 American Cancer Society. [source] Phase II study of carboxyamidotriazole in patients with advanced renal cell carcinoma refractory to immunotherapy,,§CANCER, Issue 11 2005E489, an Eastern Cooperative Oncology Group study Abstract BACKGROUND The current study evaluated the response rate and 6-month time to disease progression of the antiangiogenesis agent carboxyamidotriazole (CAI) in patients with metastatic renal cell carcinoma (RCC). METHODS Fifty-seven patients with histologically confirmed metastatic RCC that progressed after biologic therapy (interferon or interleukin-2) were enrolled. Four patients were ineligible. CAI was administered orally as a 28-day cycle. Response and time to disease progression were evaluated. RESULTS Fifteen of 53 eligible patients received > 5 cycles, but 13 patients eventually discontinued treatment because of progressive disease. The majority of toxicities were Grade 1. However, Grade 3/4 toxicities did occur, the majority of which were gastrointestinal in nature. One of 47 patients evaluable achieved a partial response (1.9%) lasting 172 days. Six of 53 patients were alive and disease progression free at 6 months from the start of treatment (11.3%). The median overall survival was 12.5 months. The survival periods in the low-risk, intermediate-risk, and poor-risk groups were 16.2 months, 20.9 months, and 5.8 months, respectively. CONCLUSIONS Patients in trials of second-line therapy appear to have a better prognosis than previously considered, in part because they are eligible for another clinical trial. CAI was found to have little to no effect on the natural history of progressive RCC. Cancer 2005. © 2005 American Cancer Society. [source] Costimulatory molecule B7-H1 in primary and metastatic clear cell renal cell carcinomaCANCER, Issue 10 2005R. Houston Thompson M.D. Abstract BACKGROUND Cancer cell expression of costimulatory molecule B7-H1 has been implicated as a potent inhibitor of T-cell,mediated antitumoral immunity. The authors recently reported that B7-H1 is aberrantly expressed in primary renal cell carcinoma (RCC). Blockade of B7-H1, as demonstrated in several murine cancer models, now represents a promising therapeutic target in RCC. However, the potential expression of B7-H1 in metastatic RCC has not been investigated. In the current study, the authors updated their primary RCC results with additional follow-up and investigated the potential role of B7-H1 in metastatic RCC. METHODS Between 2000 and 2004, 196 patients underwent nephrectomy and 26 patients had resection of RCC metastases for clear cell RCC. Immunohistochemical analysis was performed on tumor cryosections using a B7-H1 monoclonal antibody (clone 5H1). A urologic pathologist quantified the percentage of B7-H1,positive tumor cells and lymphocytes. RESULTS Variable levels of B7-H1 were expressed on primary RCC tumor cells (n = 130 [66.3%]) and primary tumor-infiltrating lymphocytes (n = 115 [58.7%]). Patients with high expression of B7-H1 on primary tumor cells and/or lymphocytes were significantly more likely to die of RCC compared with patients with low B7-H1 expression (risk ratio [RR] = 4.17; 95% confidence interval [95% CI], 1.97,8.84; P < 0.001) and this risk persisted in multivariate analysis after adjusting for the Mayo Clinic stage, size, grade, and necrosis score (RR = 2.63; 96% CI, 1.23,5.64; P = 0.013). Of the 26 metastatic specimens, cancer cell and lymphocyte B7-H1 expression were demonstrated in 17 (65.4%) and 18 (69.2%) specimens, respectively. In total, 14 (54.3%) metastatic specimens had high aggregate B7-H1 levels compared with 44.4% in primary RCC specimens. CONCLUSIONS Patients with RCC with high B7-H1 expression were significantly more likely to die even after multivariate analysis. The authors also demonstrated that a high percentage of RCC metastases similarly harbored B7-H1. The authors surmised that B7-H1 blockade may augment current immunotherapy, including patients treated for metastases after cytoreductive nephrectomy. Cancer 2005. © 2005 American Cancer Society. [source] | ||||||||||||||||||||||