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ABSTRACT: BACKGROUND: Few studies have examined factors associated with the quality of life (QOL) of patients with renal tumors. Illness uncertainty may influence QOL. OBJECTIVE: To prospectively examine the influence of uncertainty on general and cancer-specific QOL and distress in patients undergoing watchful waiting (WW) for a renal mass. DESIGN, SETTING, AND PARTICIPANTS: In 2006-2010, 264 patients were enrolled in a prospective WW registry. The decision for WW was based on patient, tumor, and renal function characteristics at the discretion of the urologist and medical oncologist in the context of the physician-patient interaction. Participants had suspected clinical stage T1-T2 disease, were aged ≥18 yr, and spoke and read English. The first 100 patients enrolled in the registry participated in this study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients completed questionnaires on demographics, illness uncertainty (Mishel Uncertainty in Illness Scale), general QOL (Medical Outcomes Study 36-item short-form survey), cancer-specific QOL (Cancer Rehabilitation Evaluation System-Short Form), and distress (Impact of Events Scale) at enrollment and at 6, 12, and 24 mo. Age, gender, ethnicity, tumor size, estimated glomerular filtration rate, comorbidities, and assessment time point were controlled for in the models. RESULTS AND LIMITATIONS: Among the sample, 27 patients had biopsies, and 17 patients had proven renal cell carcinoma. Growth rate was an average of 0.17cm/yr (standard deviation: 0.35). Mean age was 72.5 yr, 55% of the patients were male, and 84% of the patients were Caucasian. Greater illness uncertainty was associated with poorer general QOL scores in the physical domain (p=0.008); worse cancer-related QOL in physical (p=0.001), psychosocial (p<0.001), and medical (p=0.034) domains; and higher distress (p<0.001). CONCLUSIONS: This study is among the first to prospectively examine the QOL of patients with renal tumors undergoing WW and the psychosocial factors that influence QOL. Illness uncertainty predicted general QOL, cancer-specific QOL, and distress. These factors could be targeted in psychosocial interventions to improve the QOL of patients on WW.
European urology 02/2013; · 7.67 Impact Factor
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ABSTRACT: OBJECTIVES:: This study evaluated the effect of tyrosine kinase inhibitors (TKIs) on the brain metastasis (BM), local control (LC), and overall survival (OS) of patients with renal cell carcinoma (RCC) with BM. METHODS:: A retrospective review of patients with RCC BM was conducted. Eligible patients from 2 eras: pre-TKI, 2002 to 2003 and post-TKI, 2006 to 2007, were identified. Prognostic factors, use, and type of systemic therapy were noted. The timing, number, size, and treatment modality data for each BM were recorded. Use of TKI and BM treatment modality were correlated to LC and OS. RESULTS:: Eighty-one patients with 216 BMs were identified. Thirty-seven patients had BM at diagnosis and the remaining 44 were found to have BM at a later point. Forty-one patients never received a TKI and the remaining 40 received TKIs. Stereotactic radiosurgery, surgery, whole brain radiotherapy, or no local brain treatment was used for 89, 19, 24, and 75 lesions, respectively. The median OS from BM diagnosis was 5.4 months for the whole group: 4.4 versus 6.71 months in the never-TKI versus TKI groups, respectively. Patients who received TKIs post-BM development had a median OS of 23.6 months versus 2.08 and 4.41 months for the patients who received TKIs pre-BM or never-TKI, respectively (P=0.0001). LC was statistically superior in lesions managed with surgery or stereotactic radiosurgery versus the no local therapy. CONCLUSIONS:: In patients with RCC and BM, TKIs are associated with a trend of improved OS, but no significant improvement in LC of BM. They may provide a significant benefit to patients with BM with no prior TKI exposure.
American journal of clinical oncology 08/2012; · 2.21 Impact Factor
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ABSTRACT: Nephrectomy continues to be the cornerstone of treatment for localized renal cell carcinoma (RCC). Despite undergoing nephrectomy, recurrence of disease remains a concern in many patients, and different medical therapies are being investigated as means to decrease this risk. The use of the traditional immunotherapy options has not provided benefit as adjuvant treatment in this disease state. Recently, the treatment of metastatic RCC has experienced key advances with the introduction of targeted agents against the vascular endothelial growth factor (VEGF) molecule and related pathways as well as inhibitors of the mammalian target of rapamycin (mTOR), in addition to improvements in surgical technique. Additionally, there are questions about the optimal timing of systemic therapy in the context of high risk non-metastatic disease. There is optimism that locally advanced RCC might benefit from adjuvant or neoadjuvant treatment with these therapies. Ongoing clinical trials are addressing the role of targeted agents in this disease state.
Current clinical pharmacology. 08/2011; 6(3):144-50.
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ABSTRACT: Loss of chromosome 14 has been associated with poor outcomes in clear-cell renal cell carcinoma. Expression of HIFα isoforms has been linked to distinct molecular phenotypes of clear-cell renal cell carcinoma. We hypothesized that chromosome 14 loss could lead to a decrease in HIF1α levels, as its gene (HIF1A) resides in this chromosome. We analyzed 112 archival clear-cell renal cell carcinoma tumor specimens with 250K SNP microarrays. We also evaluated expression of HIFα isoforms by qPCR and immunohistochemistry in a subset of 30 patients. Loss of chromosome 14q was associated with high stage (III-IV, P=0.001), high risk for recurrence (P=0.002, RR 2.78 (1.506-5.153)) and with decreased overall survival (P=0.030) in non-metastatic clear-cell renal cell carcinoma. HIF1α mRNA and protein expression was reduced in specimens with loss of 14q (P=0.014) whereas HIF2α was not. Gain of 8q was associated with decreased overall survival (P<0.0001). Our studies confirm an association between 14q loss and clinical outcome in non-metastatic clear-cell renal cell carcinoma patients and that 8q gain is a candidate prognostic marker for decreased overall survival and appears to further decrease survival in patients with 14q loss. We have also identified that differential expression of HIF1α is associated with 14q loss. Further exploration of 8q gain, 14q loss, MYC, HIF1A and EPAS1 (HIF2α) as molecular markers of tumor behavior and prognosis could aid in personalizing medicine for patients with clear-cell renal cell carcinoma.
Modern Pathology 07/2011; 24(11):1470-9. · 4.79 Impact Factor
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ABSTRACT: Renal cell carcinoma (RCC) is the most common malignant neoplasm of the kidney, and sarcomatoid RCC is an aggressive and lethal variant. Sarcomatoid features can be seen in all types of RCC and do not constitute a separate histologic type. No cellular or genetic biomarker for the sarcomatoid variant has yet been discovered. Most systemic therapies developed for metastatic RCC are less effective in sarcomatoid RCC, although some of the cytotoxic drugs may actually be more effective for sarcomatoid RCC because of its rapid rate of proliferation. Several ongoing prospective clinical trials are investigating new drug combinations for this disease.
Expert Review of Anti-infective Therapy 06/2011; 11(6):913-20. · 2.65 Impact Factor
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ABSTRACT: This study was designed to evaluate the impact of tyrosine kinase inhibitors (TKIs) on incidence of brain metastasis (brain metastasis) and overall survival (OS) in patients with metastatic renal cell cancer (mRCC).
All patients who presented with mRCC but no brain metastasis in the intervals 2002 to 2003 and 2006 to 2007 were identified using the institutional tumor registry. The following data were collected: age, sex, Fuhrman grade, disease sites, nephrectomy, systemic therapy including TKIs (sorafenib or sunitinib), Memorial Sloan-Kettering Cancer Center risk category, brain metastasis treatment, and vital status. Statistical analysis was performed using the Cox proportional hazards model and the Kaplan-Meier method.
Of the 338 patients who were identified; 154 (46%) were treated with a TKI before brain metastasis, and 184 (54%) were not. There were no significant differences in age, histology, nephrectomy, involved sites of disease other than lung, or Memorial Sloan-Kettering Cancer Center risk category between the groups. Median OS was longer in the TKI-treated group (25 months vs 12.1 months, P < .0001). In multivariate analysis, TKI treatment (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.38-0.74; P < .001) was associated with improved OS. Forty-four (13%) patients developed a brain metastasis, including 29 (15.8%) of the non-TKI group and 15 (9.7%) of the TKI group. The 5-year actuarial rate of brain metastasis was 40% versus 17%, respectively (P < .001). TKI treatment was associated with lower incidence of brain metastasis in Cox multivariate analysis (HR, 0.39; 95% CI, 0.21-0.73; P = .003). Lung metastasis increased the risk of brain metastasis (HR, 9.61; 95% CI, 2.97-31.1; P < .001).
Treatment with TKI agents reduces the incidence of brain metastasis in mRCC. Lung metastasis is a risk factor for brain metastasis development.
Cancer 04/2011; 117(21):4958-65. · 4.77 Impact Factor
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ABSTRACT: Activated platelet-derived growth factor receptor (p-PDGFR) is frequently expressed in bone metastases of castration-resistant prostate cancer (CRPC). Phase II study of tandutinib was conducted to assess the effects of a continuously administered highly potent PDGFR inhibitor in this disease state.
Men with progressive CRPC, bone metastases, and prior taxane chemotherapy were treated with oral tandutinib 500 mg twice daily until disease progression under a two-stage design with the 8-week freedom-from-progression (FFP) rate as the primary endpoint. The trial was designed to have 87% power to reject a null FFP rate of 10% when the true rate was 33% (type I error rate = 0.02). Secondary endpoints included tumor expression of p-PDGFR, bone marker (urine N-telopeptide, serum bone-specific alkaline phosphatase) kinetics, in vivo monitoring of PDGFR inhibition in peripheral blood leukocytes, and correlation with survival.
Among 18 patients registered (aged 47-81, median 66 years), 15 were evaluable for efficacy. Five of 6 evaluable tumors were p-PDGFR positive. Mean urine N-telopeptide declined from 123.7 (baseline) to 41.0 (Cycle 2 Day 1) nmol/mmol Cr (P = 0.012). Probability of decrease in peripheral blood leukocyte p-PDGFR >0.5 versus <0.5 was associated with progression-free survival of 6 versus 8 weeks (P = 0.03, log-rank) and overall survival, 26.6 versus 42.9 weeks, respectively (P = 0.09, log-rank).
In vivo PDGFR inhibition with tandutinib correlated with accelerated disease progression. This observation raises the hypothesis that PDGF contributes to the homeostasis of bone metastases from prostate cancer.
Cancer Chemotherapy and Pharmacology 02/2011; 68(4):889-96. · 2.83 Impact Factor
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ABSTRACT: We retrospectively evaluated the feasibility, safety and outcomes of radio frequency ablation of primary renal tumors to control local disease while preserving renal parenchyma in a series of patients with metastatic renal cell carcinoma in a single institutional, multidisciplinary setting.
We evaluated the records of patients with metastatic renal cell carcinoma who underwent percutaneous radio frequency ablation of a primary renal tumor. Patient demographic and disease characteristics, adjunctive medical and surgical therapies, recurrence and clinical outcomes were studied.
A total of 15 patients treated between 2002 and 2008 met study inclusion criteria. There was no incomplete ablation or local recurrence. Ten patients had biopsy proven renal cell carcinoma in the ablated renal mass. Eight patients had a solitary metastasis, 3 had metastasis at 2 sites and 4 had 3 or more metastatic sites. Four patients experienced major complications. Median radiographic and clinical followup in patients at risk for an event was 25.5 and 33.0 months, respectively. The overall survival rate 1, 3 and 5 years after radio frequency ablation was 73.3%, 57.1% and 38.1%, respectively. At last evaluation 4 patients were in complete remission, 4 had no evidence of local recurrence but had evidence of distant disease and 7 had died of the disease.
Radio frequency ablation is feasible and safe in highly selected patients with metastatic renal cell carcinoma, resulting in durable local control as part of multimodality management and achieving renal preservation. Further investigation is required to define the role of radio frequency ablation in this patient population.
The Journal of urology 11/2010; 184(5):1882-7. · 4.02 Impact Factor
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Eric Jonasch,
Christopher G Wood,
Surena F Matin,
Shi-Ming Tu,
Lance C Pagliaro,
Paul G Corn,
Ana Aparicio,
Pheroze Tamboli,
Randall E Millikan,
Xuemei Wang,
John C Araujo,
Wadih Arap, Nizar Tannir
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ABSTRACT: To assess safety and efficacy of presurgical bevacizumab in patients with metastatic renal cell carcinoma (mRCC), and to explore the hypothesis that pretreatment of patients with antiangiogenic therapy will select patients who benefit most from cytoreductive nephrectomy.
Patients with newly diagnosed, clear cell mRCC whose primary tumors were considered resectable were enrolled. In this single-arm, phase II trial, patients received bevacizumab plus erlotinib (first patients, n = 23) or bevacizumab alone (n = 27 patients) for 8 weeks followed by restaging. If patients demonstrated progressive disease and had declining performance statuses after 8 weeks, nephrectomy procedures were deferred. Postoperatively, patients continued on the study drug or drugs if disease stabilization or regression had occurred.
Between March 2005 and March 2008, 52 patients were enrolled on study, and 50 were included in the analysis. By Memorial Sloan-Kettering Cancer Center criteria, 82% of patients had intermediate-risk, and 18% had poor-risk, features. Forty-two patients underwent nephrectomy. Median progression-free survival was 11.0 months (95% CI, 5.5 to 15.6 months). Median overall survival was 25.4 months (95% CI, 11.4 months to not estimable). Two perioperative deaths occurred; neither was attributable to study drug. Wound dehiscence resulted in treatment discontinuation for three patients and treatment delay for two others.
Presurgical treatment with bevacizumab therapy yields clinical outcomes comparable to post-surgical treatment with antiangiogenic therapy in patients with mRCC, but it may result in wound-healing delays. Prospective, randomized trials to test the use of presurgical therapy as a method to select appropriate patients for cytoreductive nephrectomy are warranted.
Journal of Clinical Oncology 08/2009; 27(25):4076-81. · 18.37 Impact Factor
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Ana Aparicio,
Brittany North,
Lindsey Barske,
Xuemei Wang,
Valentina Bollati,
Daniel Weisenberger,
Christine Yoo, Nizar Tannir,
Erin Horne,
Susan Groshen,
Peter Jones,
Allen Yang,
Jean-Pierre Issa
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ABSTRACT: Multiple clinical trials are investigating the use of the DNA methylation inhibitors azacitidine and decitabine for the treatment of solid tumors. Clinical trials in hematological malignancies have shown that optimal activity does not occur at their maximum tolerated doses but selection of an optimal biological dose and schedule for use in solid tumor patients is hampered by the difficulty of obtaining tumor tissue to measure their activity. Here we investigate the feasibility of using plasma DNA to measure the demethylating activity of the DNA methylation inhibitors in patients with solid tumors. We compared four methods to measure LINE-1 and MAGE-A1 promoter methylation in T24 and HCT116 cancer cells treated with decitabine treatment and selected Pyrosequencing for its greater reproducibility and higher signal to noise ratio. We then obtained DNA from plasma, peripheral blood mononuclear cells, buccal mucosa cells and saliva from ten patients with metastatic solid tumors at two different time points, without any intervening treatment. DNA methylation measurements were not significantly different between time point 1 and time point 2 in patient samples. We conclude that measurement of LINE-1 methylation in DNA extracted from the plasma of patients with advanced solid tumors, using Pyrosequencing, is feasible and has low within patient variability. Ongoing studies will determine whether changes in LINE-1 methylation in plasma DNA occur as a result of treatment with DNA methylation inhibitors and parallel changes in tumor tissue DNA.
Epigenetics: official journal of the DNA Methylation Society 05/2009; 4(3):176-84. · 4.58 Impact Factor
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ABSTRACT: : The standard of care for patients with advanced renal cell carcinoma (RCC) has changed to favor targeted therapy over immunotherapy. Differences in patterns of progression between patients treated with these 2 modalities, and the impact of disease stabilization on outcome, were investigated.
: Patients who progressed on first line antivascular therapy (AVT) or interferon were identified, and their medical records reviewed.
: A total of 162 patients met inclusion criteria for this analysis. Patients in the AVT group had better baseline performance status, fewer liver metastases, and more responses (CR + PR) compared with the interferon group. Both groups were equally likely to develop distant metastases; however, for patients in the AVT group, these new metastases were more likely to arise in the setting of controlled disease at baseline sites (18% vs 4%, P = .012). There was no difference in anatomic sites of progression between the 2 groups. Patients responding (CR + PR) to AVT trended toward longer progression-free survival (PFS) compared with patients with stable disease (SD) (P = .06). No difference between responders and SD was seen in the interferon group.
: Patients with RCC treated with antivascular therapy were more likely to progress at new sites in the setting of stable disease at baseline sites, suggesting that AVT may be more effective at controlling existing sites of disease than it is at preventing new metastases. Patients with SD on AVT had shorter PFS compared with responders (CR + PR). Whether this relationship extends to overall survival requires further study. Cancer 2009. (c) 2009 American Cancer Society.
Cancer 03/2009; 115(9):1859-66. · 4.77 Impact Factor
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ABSTRACT: To evaluate the effect of adjuvant thalidomide on recurrence-free survival (RFS) after nephrectomy for high-risk metastatic renal cell carcinoma (RCC).
Eligibility criteria for enrollment on this randomized trial included any histologic subtype, T2 (high grade, any N), T3/T4 (any grade, any N), or node-positive (any grade, any T) RCC. We randomized eligible patients to observation or to receive thalidomide 300 mg daily for 24 months. Patients were observed until disease recurrence or death.
After we enrolled 46 patients, we stopped the trial at a median follow up of 43.9 months (range, 9.7-74.2 months). Patients on the thalidomide arm had inferior 2- and 3-year probabilities of RFS, compared with controls (47.8% vs 69.3% and 28.7% vs 69.3%, respectively; P = .022). The 2- and 3-year cancer-specific survival was similar for both groups. All observed deaths were attributable to RCC (P = .392). By multivariate analysis, tumor size and grade predicted recurrence (P = .001 and .013) and kidney cancer-specific death (P = .002 and .014). Thalidomide treatment, however, was not an independent predictor of recurrence or cancer-specific mortality.
In this small, randomized, controlled trial, adjuvant thalidomide therapy after complete resection of high-risk RCC did not improve the 2- and 3-year RFS rates or cancer-specific death rates.
Urology 11/2008; 73(2):337-41. · 2.43 Impact Factor
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ABSTRACT: Targeted molecular therapies such as bevacizumab, sunitinib and sorafenib before surgical resection hold promise as rational treatment paradigms for patients with metastatic or locally recurrent renal cell carcinoma. To analyze the safety of this approach we evaluated surgical parameters and perioperative complications in patients treated with targeted molecular therapies before cytoreductive nephrectomy or resection of retroperitoneal renal cell carcinoma recurrence, and compared them to a matched patient cohort who underwent up-front surgical resection.
We evaluated surgical parameters and perioperative complications in 44 patients treated with targeted molecular therapies before cytoreductive nephrectomy or resection of local renal cell carcinoma recurrence, and in a matched cohort of 58 patients who underwent up-front surgery.
Cohorts of patients treated with preoperative targeted molecular therapy and initial surgical resection were matched in terms of clinical characteristics, burden of metastatic disease and number of adverse prognostic factors. A total of 39 complications occurred in 17 (39%) patients treated with preoperative targeted molecular therapy and in 16 (28%) who underwent up-front resection (p = 0.287). There were no statistically significant differences in surgical parameters, incidence of perioperative mortality, re-exploration, readmission, thromboembolic, cardiovascular, pulmonary, gastrointestinal, infectious or incision related complications between patients treated with preoperative targeted molecular therapy and those who underwent up-front surgery. Duration, type and interval from targeted molecular therapy to surgical intervention were not associated with the risk of perioperative morbidity.
Preoperative administration of targeted molecular therapies is safe, and does not increase surgical morbidity or perioperative complications in patients treated with cytoreductive nephrectomy or resection of recurrent retroperitoneal renal cell carcinoma.
The Journal of urology 08/2008; 180(1):94-8. · 4.02 Impact Factor
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ABSTRACT: Sunitinib malate is a novel multitargeted receptor tyrosine kinase inhibitor with established efficacy in the treatment of metastatic renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumor. This report describes the development of heart failure in cancer patients who received this novel agent.
A retrospective study was conducted at M. D. Anderson Cancer Center during a 1-year period on patients who received sunitinib and developed heart failure.
During 2006, 6 of 224 (2.7%) patients who received sunitinib developed heart failure (HF) that resulted in substantial morbidity and, in some cases, mortality. Symptomatic heart failure occurred soon after initiation of sunitinib (mean onset 22 days after initiation), was associated with decline in cardiac function and elevations in blood pressure, and was not completely reversible in most patients, even after termination of sunitinib therapy.
These observations suggested that sunitinib-associated heart failure may represent a potentially serious toxicity and underscore the need for careful monitoring of cardiac function and aggressive control of hypertension in these patients. Studies to elucidate potential mechanisms of heart failure and left ventricular dysfunction resulting from treatment with sunitinib are necessary to develop strategies for prevention and treatment of this complication.
Cancer 07/2008; 112(11):2500-8. · 4.77 Impact Factor
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ABSTRACT: Renal cell carcinoma affects close to 40,000 people per year in the United States; and once it is metastatic, treatment options
have historically been limited. With our emerging understanding of the molecular biology of renal cell carcinoma, we have
recently acquired an expanding armamentarium of agents that target vascular and intracellular pathways involved in renal carcinogenesis.
This chapter describes the key agents and the clinical data supporting their use. The chapter concludes with several of the
key dilemmas we will face over the next decade when approaching the treatment of renal cell carcinoma.
03/2008: pages 305-316;
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ABSTRACT: Angiogenesis is a characteristic of renal cell carcinoma. ABT-510 is an angiogenesis inhibitor that mimics the antiangiogenic properties of thrombospondin-1. This study was designed to assess the safety and efficacy of ABT-510 in patients with advanced renal cell carcinoma.
Patients with previously untreated metastatic or unresectable renal cell carcinoma were randomized to treatment with one of two doses of ABT-510, self-administered s.c. twice daily in 28-day treatment periods without intervening rest periods. End points were progression-free survival (PFS), objective response rate, overall survival, and toxicity.
The objective response rate was 4% in the 10 mg twice daily group, and there were two unconfirmed PRs in the 100 mg twice daily group. Respective median PFS was 4.2 and 3.3 months, with a 6-month PFS of 39% and 32%. Median overall survival was 27.8 months (10 mg twice daily) and 26.1 months (100 mg twice daily). The most frequent adverse events were injection site reactions (84%), fatigue (50%), headache (20%), and nausea (19%). The incidence of treatment-related, grade 3/4 adverse events was low and included three bleeding episodes (gastrointestinal hemorrhage, intracranial hemorrhage, and hemoptysis) and one thrombotic event (deep vein thrombosis). No deaths were attributed to ABT-510.
There was little evidence of clinical activity for ABT-510, and further evaluation as a single agent for treating advanced renal cell carcinoma is not warranted. The evidence of a favorable safety profile may justify further evaluation in combination therapy.
Clinical Cancer Research 12/2007; 13(22 Pt 1):6689-95. · 7.74 Impact Factor
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ABSTRACT: To our knowledge the benefit of cytoreductive surgery for patients with metastatic renal cell carcinoma with nonclear cell histology is unknown. In this retrospective study we report our experience with cytoreductive nephrectomy for nonclear cell metastatic renal cell carcinoma at M. D. Anderson Cancer Center. We compared the outcomes with those in patients with clear cell metastatic renal cell carcinoma.
From 1991 to 2006, 606 patients with metastatic renal cell carcinoma underwent cytoreductive nephrectomy and they formed the basis of this report. Of these patients 92 had nonclear cell metastatic renal cell carcinoma. The remaining 514 patients had clear cell metastatic renal cell carcinoma and they formed a comparative group. Multivariate Cox regression analysis was performed to evaluate the relationship between clinical variables and histology (clear cell vs nonclear cell) on disease specific survival.
Compared with patients with clear cell histology those with nonclear cell metastatic renal cell carcinoma were younger (p = 0.0001), and more likely to have nodal metastases (p <0.0001) and sarcomatoid features (23% vs 13%, p = 0.026). On multivariate analysis median disease specific survival in patients with nonclear cell histology was significantly worse than that in patients with clear cell metastatic renal cell carcinoma (9.7 vs 20.3 months, p = 0.0003) even after adjusting for T stage, grade, performance status, age and sarcomatoid features. Sarcomatoid features were a predictor of poor outcome in cases of clear and nonclear cell histology, although even in the absence of sarcomatoid features nonclear cell histology was associated with worse disease specific survival (p = 0.017). Interestingly although there was a significantly higher incidence of positive nodes in patients with nonclear histology (p <0.0001), this phenotype was not associated with a worse disease specific survival, as it was in those with clear cell histology (p = 0.0001). In fact, patients with node negative disease with nonclear cell histology had the worst prognosis overall in the entire group.
Patients with nonclear cell metastatic renal cell carcinoma were younger and had a higher incidence of nodal metastases, a higher incidence of sarcomatoid features and a worse prognosis than those with clear cell histology who underwent cytoreductive surgery.
The Journal of Urology 11/2007; 178(5):1896-900. · 3.75 Impact Factor
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Nizar Tannir,
Eric Jonasch,
Lance C Pagliaro,
Paul Mathew,
Arlene Siefker-Radtke,
Laurence Rhines,
Patrick Lin,
Rita Tibbs,
Kim-Anh Do,
Sue-Hwa Lin,
Shi-Ming Tu
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ABSTRACT: The purpose of the study was to evaluate the efficacy and safety of a bone-targeted regimen consisting of zoledronate, thalidomide, and interferon-gamma in patients with renal cell carcinoma and bone metastases.
Eligible patients had radiographic evidence of bone metastasis. Impending pathologic fractures or spinal cord compressions must have been controlled by surgery or radiation therapy before enrollment. Zoledronate (4 mg) was given intravenously every 4 weeks, thalidomide (300 mg) was given orally once a day, and interferon-gamma (100 microg) was given subcutaneously once a week. Patients were evaluated for time to skeletal-related events, the appearance of calcification in osteolytic metastases, and levels of the bone formation/resorption markers. RESULTS.: Fifteen patients were treated between November 2002 and November 2003; 12 had previously undergone surgery, radiation, or embolization for their bone metastases; 11 had more than 3 sites of bone involvement; and 9 also had nonosseous metastases in the lung, liver, lymph node, pancreas, or adrenal gland. The median time to progression was 8.3 weeks (range, 2.1-48 weeks). The median time to a skeletal-related event was 12.0 weeks (range, 3.9-46.4 weeks). Two patients discontinued treatment because of adverse drug reactions (1 deep venous thrombosis and 1 myocardial infarction). Two patients experienced pain improvement and developed calcification in osseous metastases; these patients also showed favorable changes in bone marker levels.
In this pilot study a bone-targeted regimen combining zoledronate, thalidomide, and interferon-gamma was well tolerated and might provide clinical benefit for a small subset of patients with renal cell carcinoma and bone metastases.
Cancer 09/2006; 107(3):497-505. · 4.77 Impact Factor
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Nizar Tannir MD,
Eric Jonasch MD,
Lance C. Pagliaro MD,
Paul Mathew MD,
Arlene Siefker-Radtke MD,
Laurence Rhines MD,
Patrick Lin MD,
Rita Tibbs MD,
Kim-Anh Do PhD,
Sue-Hwa Lin PhD, [......],
Eric Jonasch,
Lance C. Pagliaro,
Paul Mathew,
Arlene Siefker‐Radtke,
Laurence Rhines,
Patrick Lin,
Rita Tibbs,
Kim‐Anh Do,
Sue‐Hwa Lin,
Shi‐Ming Tu
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ABSTRACT: BACKGROUND.The purpose of the study was to evaluate the efficacy and safety of a bone-targeted regimen consisting of zoledronate, thalidomide, and interferon-γ in patients with renal cell carcinoma and bone metastases.METHODS.Eligible patients had radiographic evidence of bone metastasis. Impending pathologic fractures or spinal cord compressions must have been controlled by surgery or radiation therapy before enrollment. Zoledronate (4 mg) was given intravenously every 4 weeks, thalidomide (300 mg) was given orally once a day, and interferon-γ (100 μg) was given subcutaneously once a week. Patients were evaluated for time to skeletal-related events, the appearance of calcification in osteolytic metastases, and levels of the bone formation/resorption markers.RESULTS.Fifteen patients were treated between November 2002 and November 2003; 12 had previously undergone surgery, radiation, or embolization for their bone metastases; 11 had more than 3 sites of bone involvement; and 9 also had nonosseous metastases in the lung, liver, lymph node, pancreas, or adrenal gland. The median time to progression was 8.3 weeks (range, 2.1–48 weeks). The median time to a skeletal-related event was 12.0 weeks (range, 3.9–46.4 weeks). Two patients discontinued treatment because of adverse drug reactions (1 deep venous thrombosis and 1 myocardial infarction). Two patients experienced pain improvement and developed calcification in osseous metastases; these patients also showed favorable changes in bone marker levels.CONCLUSIONS.In this pilot study a bone-targeted regimen combining zoledronate, thalidomide, and interferon-γ was well tolerated and might provide clinical benefit for a small subset of patients with renal cell carcinoma and bone metastases. Cancer 2006. © 2006 American Cancer Society.
Cancer 07/2006; 107(3):497 - 505. · 4.77 Impact Factor
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ABSTRACT: The primary objective of the current study was to evaluate the effectiveness of capecitabine and gemcitabine in the treatment of patients with androgen-independent prostate cancer (AIPCa) who experienced disease progression after taxane therapy. The secondary objective was to evaluate the safety and tolerability of the combination of capecitabine and gemcitabine in these patients.
Patients with AIPCa, either metastatic or unresectable disease, and prior taxane therapy were eligible. Patients were treated with 800 mg/m2 of capecitabine orally twice daily (1600 mg/m2 per day) for 14 days, and 800 mg/m2 of gemcitabine intravenously on Days 1 and 8. This regimen was repeated every 21 days. Response to therapy was determined by measuring prostate-specific antigen concentration.
Sixteen patients participated in this study from June 2003 to January 2004. There were no responses as defined by a 50% decline in prostate-specific antigen. The study was terminated early because the response rate was not projected to exceed 30% (rejection error of 10%). Toxicities were notable: 3 patients had Grade 3 thrombocytopenia, 4 patients had Grade 3 neutropenia, and 3 patients had Grade 3 infections (according to the National Cancer Institute Common Toxicity Criteria [version 2.0]). Eight patients (50%) required dose reduction or treatment interruption.
The combination of capecitabine and gemcitabine for the salvage treatment of patients with AIPCa was associated with significant toxicities and was ineffective for induction of disease regression.
Cancer 06/2006; 106(10):2143-7. · 4.77 Impact Factor
