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Although myeloid growth factors are commonly used to treat metastatic castration-resistant prostate cancer (mCRPC), the optimal timing of administration has not been well studied. We assessed the effects of same-day pegfilgrastim, a neutrophil stimulator, after cabazitaxel treatment with or without carboplatin in patients with mCRPC. We also evaluated the frequency of urinary tract inflammation during treatment.Between September 2010 and September 2014, 151 consecutive patients with mCRPC underwent cabazitaxel treatment with or without the addition of carboplatin at a single institution. We assessed absolute neutrophil count recovery, incidence of neutropenia, neutropenic fever, antibiotic usage, treatment delays or discontinuation, dose reduction, and hospitalization with pegfilgrastim administration. Radiologists blinded to therapy reviewed computed tomography scans to detect urinary tract inflammation.The median patient age was 69 years (range, 41-88 years); 78% of patients were white, and 54% had a Gleason score ≥ 9. Median overall survival was 9 months (95% confidence interval, 8-11 months). One patient (1%) had neutropenia; 38 patients (25%) had infection. During cycle 1, a significantly higher proportion of patients receiving pegfilgrastim after 24 hours developed infection than did those receiving pegfilgrastim the same day (26% vs. 6%; P = .01).Same-day pegfilgrastim administration after cabazitaxel treatment with or without carboplatin in patients with mCRPC is feasible. The urinary tract inflammation rate (21%) was higher than that reported anecdotally. Results need to be prospectively validated.

Background Pazopanib is associated with increased progression-free survival (PFS) in clear-cell renal cell carcinoma (RCC) and has become a standard of care in this disease. The drug is used in metastatic non–clear-cell RCC, but data on outcomes in this setting are limited. Patients and Methods We conducted a retrospective data analysis of records of consecutive metastatic non–clear-cell RCC patients who received pazopanib in front-line and salvage settings between November 2009 and November 2012. Tumor response rate was assessed by a blinded radiologist using Response Evaluation Criteria in Solid Tumors version 1.1. PFS and overall survival (OS) times were estimated using Kaplan–Meier methods. Results Twenty-nine patients were identified with non–clear-cell metastatic RCC, 9 received pazopanib in the front-line setting, 20 in the salvage setting after progression of disease with other targeted therapies. Seven patients (24%) had papillary RCC, 4 (14%) had chromophobe, 5 (17%) had unclassified histopathology, and 13 (45%) had other subtypes including collecting duct, translocation Xp11.2, and various subtypes with sarcomatoid differentiation. All patients discontinued pazopanib before analysis. Median PFS was 8.1 months (95% CI, 5.7-NA [not available]) in the front-line group, and 4 months (95% CI, 2.1-9.9) in the salvage group. Median OS was 31 months (95% CI, 9.2-NA) in the front-line group, and 13.6 months (95% CI, 6.4-NA) in the salvage group. Conclusion Pazopanib showed efficacy in patients with metastatic non–clear-cell RCC in the front-line and salvage settings. Toxicity was mild to moderate and manageable. Further studies are needed to evaluate pazopanib's role in non–clear-cell RCC in terms of efficacy and safety.

Purpose The development and implementation of a pharmacy-driven, postdischarge follow-up telephone call program to assess medication adherence, provide education, and address medication-related concerns are discussed. Summary Many readmissions are avoidable through effective discharge planning and patient follow-up after hospitalization. However, there is limited information on how to effectuate this process. To address this barrier, a team consisting of a clinical pharmacy specialist, a clinical pharmacy manager, a postgraduate year 1 pharmacy resident, and an education specialist at The University of Texas MD Anderson Cancer Center collaborated to create a postdischarge telephone call program within a transitions-of-care (TOC) pilot program. Various education and training materials were created to ensure trainees were competent. As of February 2016, 23 outpatient pharmacists and students have completed training, earning a median pretest and posttest score of 6 and 9, respectively, out of 10. There have been 206 calls completed; 150 patients (73%) were successfully reached, and 20 patients (9%) declined the telephone call. Medication adherence assessed during the telephone follow-up identified that 134 patients (89%) received their new medications within 72 hours, and 87 patients (58%) were recognized as having one or more discrepancies. Conclusion Developing a TOC program similar to this pilot program requires several resources including time, collaboration, and support from the management team. Pharmacy is well positioned to complete an accurate medication review and conduct postdischarge telephone calls to address medication-related issues. By providing these services, patients will receive continuity of care and positively impact emergency room visitation rates and hospital readmission rates.

We identified sunitinib alternative schedules that maintained dose intensity while decreasing adverse events in patients with metastatic renal cell cancer. We also determined the impact of alternative schedules on clinical outcomes.We retrospectively reviewed the records of patients 18 years old or older with clear cell metastatic renal cell cancer who received first line sunitinib between January 26, 2006 and March 1, 2011 at our major comprehensive cancer center. A subset of patients was switched at the first intolerable adverse event from the traditional schedule of 28 days on and 14 days off to a schedule of 14 days on and 7 days off or other alternative schedules. A control group underwent standard dose reduction. We estimated progression-free and overall survival by the Kaplan-Meier method. Predictors of progression-free and overall survival were analyzed using Cox regression.A total of 187 patients were included in analysis, of whom 87% were on the traditional schedule at baseline. During treatment 53% of patients continued on the traditional schedule and 47% began or were transitioned to alternative schedules. Baseline characteristics were similar. Adverse events prompting schedule modification included fatigue in 64% of cases, hand-foot syndrome in 38% and diarrhea in 32%. Median time to alternative schedules was 5.6 months. Median overall survival was 17.7 months (95% CI 10.8-22.2) on the traditional schedule compared to 33.0 months (95% CI 29.3-not estimable) on alternative schedules (p0.0001). On multivariable analysis poor Eastern Cooperative Oncology Group (ECOG) performance status, increased lactate dehydrogenase, decreased albumin, unfavorable Heng criteria and the traditional schedule were associated with decreased overall survival (p0.05).Sunitinib administered on alternative schedules may mitigate adverse events while achieving outcomes comparable to those of the traditional schedule in patients with metastatic renal cell cancer. Prospective investigations of alternate dosing schemas are warranted.

Purpose: We sought to investigate if the use of HMG Co-A reductase inhibitors (statins) has an impact on outcomes among patients with triple negative breast cancer (TNBC). Methods: We reviewed the cases of women with invasive, non-metastatic TNBC, diagnosed 1997-2012. Clinical outcomes were compared based on statin use (defined as ever use during treatment vs. never use). We identified a subset of women for whom a 5-value lipid panel (5VLP) was available, including total cholesterol, low density lipoprotein, high density lipoprotein, very low density lipoprotein, and triglycerides. The Kaplan-Meier method was used to estimate median overall survival (OS), distant metastases-free survival (DMFS), and local-regional recurrence-free survival (LRRFS). A Cox proportional hazards regression model was used to test the statistical significance of prognostic factors. Results: 869 women were identified who met inclusion criteria, with a median follow-up time of 75.1 months (range 2.4-228.9 months). 293 (33.7%) patients used statins and 368 (42.3%) had a 5VLP. OS, DMFS, and LRRFS were not significant based on statin use or type. Controlling for the 5VLP values, on multivariable analysis, statin use was significantly associated with OS (HR 0.10, 95% CI 0.01-0.76), but not with DMFS (HR 0.14, 95% CI 0.01-1.40) nor LRRFS (HR 0.10 95% CI 0.00-3.51). Conclusions: Statin use among patients with TNBC is not associated with improved OS, although it may have a benefit for a subset of patients. Prospective assessment would be valuable to better assess the potential complex correlation between clinical outcome, lipid levels, and statin use.

Objective To characterise the incidence, onset, management, predictors, and clinical impact of mammalian target of rapamycin (mTOR) inhibitor-associated non-infectious pneumonitis (NIP) on patients with metastatic renal cell carcinoma (mRCC). Patients and Methods Retrospective review of 310 patients with mRCC who received temsirolimus and/or everolimus between June 2007 and October 2010. Clinical correlations were made with serial radiological imaging. Fisher's exact, Wilcoxon rank-sum, and logistic regression analyses were used to evaluate the association of NIP with demographic or clinical factors. Log-rank and Cox proportional hazards regression analyses were used for the time-to-event analysis. Results NIP occurred in 6% of temsirolimus-treated and 23% of everolimus-treated patients. Symptoms included cough, dyspnoea, and fever (median of two and three symptoms per patient, respectively). The median National Cancer Institute Common Toxicity Criteria for Adverse Events pneumonitis grade was 2 for both groups. Older age and everolimus treatment were predictive of NIP. Patients who developed NIP had a significantly longer time on treatment (median 4.1 vs 2 months) and overall survival (OS) (median 15.4 vs 7.4 months). NIP was a predictor of improved OS by multivariate analysis. Conclusions There was an increased incidence of NIP in everolimus-treated patients. Improved OS in patients who developed NIP is an intriguing finding and should be further investigated. Given the incidence, morbidity, and outcomes seen in patients on everolimus who develop NIP, management should include proactive monitoring and treatment of NIP with the goal of preserving mTOR inhibitor therapy.

Aim The multi-tyrosine kinase inhibitor pazopanib prolongs progression-free survival (PFS) versus placebo in treatment-naive and cytokine-refractory metastatic clear-cell renal cell carcinoma (ccRCC). Outcomes and safety data with pazopanib after targeted therapy (TT) are limited. Methods We retrospectively evaluated records of consecutive patients with metastatic ccRCC who had progressive disease (PD) after TT and received pazopanib from November 2009 through November 2011. Tumour response was assessed by a blinded radiologist using Response Evaluation Criteria In Solid Tumours (RECIST). PFS and overall survival (OS) were estimated by Kaplan–Meier methods. Results Ninety-three patients were identified. Median number of prior TTs was 2 (range, 1–5). There were 68 events (PD or death). Among 85 evaluable patients, 13 (15%) had a partial response. Median PFS was 6.5 months (95% CI: 4.5–9.7); median OS was 18.1 months (95% CI: 10.26–NA). Common adverse events (AEs) included fatigue (44%), elevated transaminases (35%), diarrhoea (30%), hypothyroidism (18%), nausea/vomiting (17%), anorexia (14%) and hypertension exacerbation (14%); 91% of AEs were grade 1/2. Eleven patients (12%) discontinued therapy due to AEs. There were no treatment-related deaths. Concluding statement Pazopanib demonstrated efficacy in patients with metastatic ccRCC after PD with other TTs. Toxicity overall was mild/moderate and manageable.

Bone metastases (BMs) occur commonly in patients with metastatic renal cell carcinoma (mRCC). Tyrosine kinase inhibitors (TKIs) have improved the outcomes for patients with mRCC. However, data on the outcomes of mRCC patients with BMs treated with TKIs are limited. We describe the outcomes of patients with BMs treated with TKI therapy and compare them with the outcomes from a pre-TKI group.Using an institutional tumor registry, a retrospective review of patients with mRCC from 2002 to 2003 and 2006 to 2007 was performed. The baseline characteristics were analyzed, and overall survival (OS) was estimated using the Kaplan-Meier method. The predictors of OS were analyzed using Cox regression analysis.The data from 375 patients were reviewed. Of these patients, 188 (50%) started treatment with TKIs and 187 (50%) had started treatment in the pre-TKI era. The distribution of patient characteristics was similar. The sites of organ metastases were equally distributed, including BMs in 48% of the patients in each cohort. The median OS for the patients treated in the TKI era was 22 months (95% confidence interval [CI], 17-25 months) compared with 14 months (95% CI, 10-19 months; P .01) for the historical controls. A subset analysis of patients with BM in the TKI era demonstrated a median OS of 24 months (95% CI, 17-28 months) compared with 18 months (95% CI, 10-21 months; P .01) in pre-TKI era. The predictors of shorter OS were a higher Memorial Sloan Kettering Cancer Center score; liver, lung, and brain metastases; and multiple sites of BMs (hazard ratio, 1.38; 95% CI, 1.02-1.91; P = .04). The rate of new BM development was the same in the pre- and post-TKI era.The rate of BM development was the same in the pre- and post-TKI era. The management of BMs in patients with mRCC remains challenging.

Objective To explore the efficacy and safety of pazopanib in a ‘real-world’ setting in unselected patients, as data regarding unselected patients with metastatic clear-cell renal cell carcinoma (ccRCC) treated with first-line pazopanib are limited. Patients and Methods We reviewed records of patients with metastatic ccRCC treated with first-line pazopanib from 1 November 2009 through to 1 November 2012. Cox models were fitted to evaluate the association of progression-free survival (PFS) and overall survival (OS) with patient co-variables. Results In all, 88 patients were identified; 74 were evaluable for response: two (3%) had a complete response, 27 (36%) a partial response, 36 (49%) had stable disease and nine (12%) had progressive disease. The median PFS was 13.7 months [95% confidence interval (CI) 8.7–18.3]. PFS was correlated with a Karnofsky Performance Status score of 1.5 × upper limit of normal (HR 3.25, P = 0.014). The median OS was 29.1 months (95% CI 20.2–not reached). The OS was correlated with brain metastasis (HR 2.55, P = 0.009), neutrophilia (HR 1.179, P = 0.018), and anaemia (HR 3.51, P < 0.001). There were no treatment-related deaths. In all, 53 patients received second-line therapy [vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) in 22 patients, mammalian target of rapamycin inhibitors (mTORi) in 22 patients, and other therapy in nine patients]; the median PFS was 8.6 months (95% CI 3.3–25.7) with VEGFR-TKI and 5 months (95% CI 3.5–15.2) with mTORi (P = 0.41); the median OS was 19.9 months (95% CI 12.9–not reached) and 14.2 months (95% CI 8.1–not reached), from initiation of second-line VEGFR-TKI or mTORi, respectively (P = 0.37). Conclusions In this retrospective study, first-line pazopanib confirmed its efficacy in metastatic ccRCC. Trends for longer PFS and OS were seen with VEGFR-TKI compared with mTORi after first-line pazopanib.

Insights into renal cell carcinoma (RCC) biology have greatly expanded the treatment armamentarium for metastatic RCC (mRCC). Since 2005, six targeted agents have been approved by the US Food and Drug Administration (FDA) for the management of mRCC, and many new targeted therapies are in development. A number of novel VEGF Inhibitors/Multi-Tyrosine Kinase Inhibitors are currently in various stages of development. New targeted agents with novel mechanisms of action are also being studied, including Histone Deacetylase Inhibitors, Angiopoietin/TIE-2 inhibitors, Carbonic anhydrase IX inhibitors, vaccines, and others. In addition to combining currently available immunologic therapies with emerging agents, researchers are also developing novel immunologic therapies to treat mRCC, including those that block Cytotoxic T-Lymphocyte Antigen 4 (CTLA4). Several trials evaluating combinations and sequential therapy of targeted agents have been published, and several others are underway. Trials of special mRCC populations, including poor-risk disease, non-clear cell RCC (NCC-RCC), and papillary type RCC are further refining the use of targeted treatments. As new targeted agents emerge and therapies with novel mechanisms of action are developed, the treatments options available for metastatic RCC are expected to increase. New therapies will likely have fewer detrimental side effects and better efficacy, leading to better quality of life for patients.

Insights into the biology of clear-cell renal cell carcinoma (CCRCC) have identified multiple pathways associated with the pathogenesis and progression of this cancer. This progress has led to the development of multiple agents targeting these pathways, including the tyrosine kinase inhibitors sorafenib, sunitinib, and pazopanib, the monoclonal antibody bevacizumab, and the mTOR inhibitors temsirolimus and everolimus. With the exception of temsirolimus, phase 3 trials tested these agents in patients with clear-cell histology; therefore, their efficacy in non-CCRCC is unclear. To date, there is no established effective therapy for patients with advanced non-CCRCC. This article focuses on treatment options for metastatic non-CCRCC.

Objective • To investigate the effect of combining gemcitabine plus capecitabine (GX) with bevacizumab (A) in patients with metastatic RCC previously treated with cytokines and targeted agents. Methods • The combination of GX + A was evaluated in patients with metastatic RCC using institutional databases. • Data included demographics, previous therapies, number of metastatic sites, Memorial Sloan-Kettering Cancer Center risk stratification variables, and previous nephrectomy status. • Descriptive statistics and survival analysis were employed for data analysis. Results • Between January 2005 and October 2008, 28 patients were identified. Mean age was 55.7 years. Fifteen (53.57%) patients had been given tyrosine kinase inhibitor (TKI) previously. Nine (32.14%) patients had clear cell histology, 10 (35.71%) patients had sarcomatoid features on histopathology, and 19 patients (67.86%) had a prior nephrectomy. • Initial treatment consisted of G (mean dose 786.07 mg/m²) every 2 weeks, X (mean dose 2.73 g/day), and A (mean dose 10 mg/kg) every 2 weeks. Median progression-free survival (PFS) was 5.9 months and the median overall survival (OS) was 10.4 months. • In patients with previous TKI therapy, median PFS was 6.2 months and median OS was 11.7 months. • In patients with sarcomatoid features, median PFS was 3.9 months and OS was 9.0 months. • Three patients discontinued one or more of the drugs because of adverse reactions. Conclusions • The combination of GX + A shows potential efficacy and acceptable tolerability in patients with intermediate and poor prognosis metastatic RCC. • Based on these observations, a phase II trial is now underway assessing this combination in patients with sarcomatoid RCC.

To identify the clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) with pancreatic metastases (PM) treated with either pazopanib or sunitinib and assess whether PM is an independent prognostic variable in the current therapeutic environment.A retrospective review of patients with mRCC in an outpatient clinic was carried out for the period January 2006 to November 2011. Patient characteristics, including demographics, laboratory data and outcomes, were analysed. Baseline characteristics were compared using chi-squared and t-tests and overall survival (OS) and cancer-specific survival (CSS) rates were estimated using Kaplan-Meier methods. Predictors of OS were analysed using Cox regression.A total of 228 patients were reviewed, of whom 44 (19.3%) had PM and 184 (81.7%) had metastases to sites other than the pancreas. The distribution of baseline characteristics was equal in both groups, with the exception of a higher incidence of previous nephrectomy, diabetes and number of metastatic sites in the PM group. Four patients had isolated PM, but the majority of patients (68%) with PM had at least three different organ sites of metastases, as compared with 29% in patients without PM (P0.01). The distribution of organ sites of metastases was similar, excluding the pancreas, in those with and those without PM (P0.05). The median OS was 39 months (95% confidence interval [CI] 24-57, hazard ratio 0.66, 95% CI 0.42-0.94; P = 0.02) for patients with PM, compared with 26 months (95% CI 21-31) for patients without PM (P0.01). CSS was 42 months (95% CI 30-57) in the PM group and 27 months (95% CI 22-33) in the control group (P = 0.05).Despite a higher number of affected organ sites in the PM cohort, mRCC behaviour in this cohort appears to be more indolent, as demonstrated by a higher median OS. These findings suggest that host or tumour features associated with PM may represent a less aggressive tumour phenotype.

Purpose: We previously demonstrated that cholesterol-lowering agents regulate radiation sensitivity of inflammatory breast cancer (IBC) cell lines in vitro and are associated with less radiation resistance among IBC patients who undergo postmastectomy radiation. We hypothesized that decreasing IBC cellular cholesterol induced by treatment with lipoproteins would increase radiation sensitivity. Here, we examined the impact of specific transporters of cholesterol (ie lipoproteins) on the responses of IBC cells to self-renewal and to radiation in vitro and on clinical outcomes in IBC patients. Methods and Materials: Two patient-derived IBC cell lines, SUM 149 and KPL4, were incubated with low-density lipoproteins (LDL), very-low-density lipoproteins (VLDL), or high-density lipoproteins (HDL) for 24 hours prior to irradiation (0-6 Gy) and mammosphere formation assay. Cholesterol panels were examined in a cohort of patients with primary IBC diagnosed between 1995 and 2011 at MD Anderson Cancer Center. Lipoprotein levels were then correlated to patient outcome, using the log rank statistical model, and examined in multivariate analysis using Cox regression. Results: VLDL increased and HDL decreased mammosphere formation compared to untreated SUM 149 and KPL4 cells. Survival curves showed enhancement of survival in both of the IBC cell lines when pretreated with VLDL and, conversely, radiation sensitization in all cell lines when pretreated withmore » HDL. In IBC patients, higher VLDL values (>30 mg/dL) predicted a lower 5-year overall survival rate than normal values (hazard ratio [HR] = 1.9 [95% confidence interval [CI]: 1.05-3.45], P=.035). Lower-than-normal patient HDL values (

With the approval of several new agents for the treatment of renal cell carcinoma (RCC) since 2005, the outlook for patients with metastatic disease is improving. The three major classes of agents available to clinicians are immunotherapy, antiangiogenic agents, and mammalian target of rapamycin (mTOR) inhibitors. A number of questions arise on how to best use these therapies, including which sequence to use, whether combinations of agents provide superior outcome compared to monotherapy, and whether predictive biomarkers exist to help guide treatment decision making in patients with metastatic RCC. Based on our current knowledge, combination therapy has not yet succeeded in increasing clinical benefit, and is associated with substantial toxicity. Sequencing is generally safe, with the exception of high-dose interleukin-2 following antiangiogenic therapy. As of now, no useful biomarkers exist to guide treatment decisions. With our evolving understanding of RCC tumor biology, we anticipate that new therapeutic targets will be discovered, and predictive biomarkers will be developed that will aid in improving both combination and sequential therapy for this disease.

Background Vascular endothelial growth factor receptor inhibitors, mammalian target of rapamycin inhibitors, and tyrosine kinase inhibitors are approved for metastatic renal cell cancer. Proteinuria can occur, but there is limited data regarding the incidence, monitoring, and management in metastatic renal cell cancer patients. Objective Our primary objective was to describe the incidence and severity of proteinuria in metastatic renal cell cancer patients treated in the first-line setting with pazopanib, bevacizumab, or everolimus. Methods We conducted a retrospective review of patients with metastatic renal cell cancer enrolled from January 2011–April 2013 in a phase II trial. Baseline and toxicity data were extracted from the electronic medical record. Descriptive statistics were used. Results In all, 129 patients were eligible for analysis. The overall incidence of proteinuria was 81%, with most events being Grade 1 or 2. The incidence of proteinuria was 80% ( n = 35) for pazopanib, 64% ( n = 25) for bevacizumab, and 96% ( n = 44) for everolimus. At peak proteinuria, 80% ( n = 28), 64% ( n = 16), and 80% ( n = 35) of patients on pazopanib, bevacizumab, and everolimus, respectively, were managed with continued monitoring at the same dose. The overall incidence of Grades 3 and 4 events was 24% ( n = 6) and found in the bevacizumab group. Conclusion A high incidence of proteinuria with minor severity within each class was demonstrated. It may be reasonable to continue therapy at the same dose for Grade 1 or 2 proteinuria. Treatment modification or discontinuation of therapy may be warranted with Grade 3 or 4 proteinuria.

Denosumab is approved for the prevention of skeletal-related events (SREs) in metastatic solid tumor patients with bone metastases. Limited data regarding the safety of denosumab in patients with severe renal insufficiency suggests increased rates of hypocalcemia compared to patients with normal renal function. The purpose of this study was to assess the rates of hypocalcemia and hypophosphatemia in cancer patients with severe renal impairment. In this case series, patient demographics, primary tumor site, number of denosumab doses, and episodes of hypocalcemia and hypophosphatemia were retrospectively obtained by patient chart review. Estimated glomerular filtration rate (eGFR) was calculated using the Cockcroft-Gault equation. Twenty-two metastatic solid tumor patients with severe renal insufficiency (creatinine clearance

Other than skin cancer, prostate cancer is the most frequently diagnosed cancer in men, and it is the second leading cause of cancer-related death for males in the United States. Screening for prostate cancer using prostate-specific antigen testing became widely used by the late 1980s, augmenting the digital rectal exam. This led to a decline in the percentage of prostate cancer cases that were metastatic at diagnosis and a decrease in prostate cancer mortality. But some argued it led to overtreatment of prostate cancers as well. Recently, the U.S. Preventive Services Task Force (USPSTF) issued recommendations against routine prostate cancer screening in asymptomatic patients. The recent recommendations have created much controversy among medical professionals, patient advocate groups, and the general public. Most prostate cancer screening recommendations from professional organizations agree that an informed discussion and review of each individual patient's clinical situation should drive the decision to screen or not to screen, but the current USPSTF recommendations largely remove patient and provider autonomy in this regard. They do not contribute toward personalized screening based on individualized patient risk profiles, characteristics, and preferences.

To characterise the incidence, onset, management, predictors, and clinical impact of mammalian target of rapamycin (mTOR) inhibitor-associated non-infectious pneumonitis (NIP) on patients with metastatic renal cell carcinoma (mRCC).Retrospective review of 310 patients with mRCC who received temsirolimus and/or everolimus between June 2007 and October 2010. Clinical correlations were made with serial radiological imaging. Fisher's exact, Wilcoxon rank-sum, and logistic regression analyses were used to evaluate the association of NIP with demographic or clinical factors. Log-rank and Cox proportional hazards regression analyses were used for the time-to-event analysis.NIP occurred in 6% of temsirolimus-treated and 23% of everolimus-treated patients. Symptoms included cough, dyspnoea, and fever (median of two and three symptoms per patient, respectively). The median National Cancer Institute Common Toxicity Criteria for Adverse Events pneumonitis grade was 2 for both groups. Older age and everolimus treatment were predictive of NIP. Patients who developed NIP had a significantly longer time on treatment (median 4.1 vs 2 months) and overall survival (OS) (median 15.4 vs 7.4 months). NIP was a predictor of improved OS by multivariate analysis.There was an increased incidence of NIP in everolimus-treated patients. Improved OS in patients who developed NIP is an intriguing finding and should be further investigated. Given the incidence, morbidity, and outcomes seen in patients on everolimus who develop NIP, management should include proactive monitoring and treatment of NIP with the goal of preserving mTOR inhibitor therapy.

Limited data are available regarding patients with renal cell carcinoma and ESRD treated with TTs. The objective of this study was to explore the tolerability and safety of TT in patients with mRCC and ESRD.We retrospectively identified patients with mRCC and ESRD treated at the University of Texas M.D. Anderson Cancer Center from 2002 to 2012. Patient characteristics including demographic, histology, treatment, and adverse events are reported. Duration of treatment (TOT) was determined from date of drug initiation to discontinuation. Overall survival (OS) was determined from initiation of TT to death. Statistics are descriptive.Fourteen patients were identified. Ten patients had clear-cell histology and 4 had papillary histology. The median number of TTs per patient was 3 (range, 1-4) with median TOT of 28 months for all TTs. Eighty-eight percent of all toxicities were Grade 1 to 2; no Grade 4 toxicities were noted. Treatment discontinuations included 3 patients treated with sorafenib due to hand-foot syndrome, intolerable fatigue, and squamous cell skin cancer development; 2 patients treated with pazopanib due to intolerable fatigue and increased transaminase levels; and 1 patient treated with everolimus due to pneumonitis. Eight patients died from progressive disease. Median OS from initiation of TT was 28.5 months and 35 months from time of diagnosis.Toxicities were mild to moderate and consistent with those reported in previous studies. TTs appear to be safe, well tolerated and produce antitumor response in patients with mRCC and ESRD receiving dialysis.

Sipuleucel-T is an immunotherapy indicated for the treatment of metastatic prostate cancer. It offers a new mechanism to treat prostate cancer without the side effects of hormone therapies and chemotherapies. In previous studies sipuleucel-T did not delay disease progression, but demonstrated an overall survival benefit compared to placebo. While clinical trials have evaluated the effects of sipuleucel-T on overall survival and progression, more studies are needed to evaluate its effectiveness and role in the management of prostate cancer. The objective of this study is to identify the incidence and possible predictors for disease progression in patients receiving sipuleucel-T. A retrospective review of patients who received sipuleucel-T between 1 September 2010 and 11 October 2011 was conducted (n = 36). Patients who changed therapy or died within 120 days were classified as experiencing rapid progression. Potential predictors of rapid progression were examined using logistic regression. Seven patients met criteria for rapid progression. Progression occurred in 72.2% of all patients. The median days to progression was 158. No significant predictors of rapid progression were identified. Currently no predictors have been found to be associated with rapid progression in prostate cancer patients on sipuleucel-T.

e16513Background: Cabazitaxel (CBZ) is a novel taxane approved after docetaxel in patients (pts) with metastatic castration resistant prostate cancer (mCRPC). Though myeloid growth factors are comm...

Sorafenib and sunitinib are oral tyrosine kinase inhibitors, commonly used in the treatment of metastatic renal cell carcinoma. Known adverse events associated with tyrosine kinase inhibitors include hypertension and palmarplantar erythrodysesthesia. We report two cases of acute pancreatitis associated with tyrosine kinase inhibitors.

There are limited studies characterizing cancer-related symptoms in outpatient advanced prostate cancer patients. The aim of this retrospective study was to describe the impact of an outpatient palliative care (PC) consultation on symptoms in patients with advanced prostate cancer.We retrospectively reviewed the medical records of 55 consecutive patients with advanced prostate cancer seen in our institution's outpatient PC center. Information regarding demographics, disease status, Edmonton Symptom Assessment System (ESAS) scores, Eastern Cooperative Oncology Group (ECOG) Performance Status, laboratory data, and pharmacological interventions were analyzed.The median age of the study's patients was 66 years old, with 73% Caucasian ethnicity. All patients had metastatic disease and 96% had received prior cytotoxic chemotherapy. The most frequently occurring symptoms upon presentation were pain, fatigue, and drowsiness (50%). Pain and fatigue were also the most severe symptoms, each having median ESAS scores of 7 (on a 0-10 scale). We instituted a median of 3 pharmacological interventions per patient, with a median of 15 days to follow-up assessment. At follow-up, patients reported significant symptom improvements in pain, drowsiness, fatigue, depression, sleep, sense of well-being, and anxiety.Based on our preliminary data, we conclude that patients with advanced prostate cancer referred to PC experience severe and clinically significant symptoms. An outpatient PCconsultation is associated with significant symptom improvement in this subset of a distressed population. Future prospective studies are warranted to further describe symptom burden and the role for outpatient PC for advanced prostate cancer patients.

In April 2010, sipuleucel-T became the first anticancer vaccine approved by the United States Food and Drug Administration. Different from the traditional chemotherapy agents that produce widespread cytotoxicity to kill tumor cells, anticancer vaccines and immunotherapies focus on empowering the immune system to overcome the tumor. The immune system consists of innate and adaptive components. The CD4(+) and CD8(+) T cells are the most crucial components of the adaptive arm of the immune system that act to mediate antitumor responses. However, T-cell responses are regulated by intrinsic and extrinsic mechanisms, which may interfere with effective antitumor responses. Many anticancer immunotherapies use tumor-associated antigens as vaccines in order to stimulate an immune response against tumor cells. Sipuleucel-T is composed of autologous mononuclear cells incubated with a fusion protein consisting of a common prostate cancer antigen (prostatic acid phosphatase) linked to an adjuvant (granulocyte-macrophage colony-stimulating factor). It is postulated that when the vaccine is infused into the patient, the activated antigen-presenting cells displaying the fusion protein will induce an immune response against the tumor antigen. In a recent randomized, double-blind, placebo-controlled, phase III clinical trial, sipuleucel-T significantly improved median overall survival by 4.1 months in men with metastatic castration-resistant prostate cancer compared with placebo. Although overall survival was improved, none of the three phase III clinical trials found a significant difference in time to disease progression. This, along with cost and logistic issues, has led to an active discussion. Although sipuleucel-T was studied in the metastatic setting, its ideal place in therapy is unknown, and clinical trials are being conducted in patients at different stages of disease and in combination with radiation therapy, antiandrogen therapy, and chemotherapy. Various other anticancer vaccines and immunotherapies for other tumor types are currently under investigation and in clinical trials. These immunotherapies were formulated to incorporate tumor-associated antigens aimed at stimulating effector T-cell responses or to block regulatory mechanisms that suppress the function of effector T cells. Additional studies will determine how these therapies can best improve clinical outcomes in patients with cancer.

Objective To report a case of severe rhabdomyolysis resulting in acute renal failure caused by an interaction between ketoconazole and simvastatin in a patient with prostate cancer. Case summary A 64-year-old man who received ketoconazole for prostate cancer, along with simvastatin and fenofibrate for dyslipidemia, presented to our ambulatory clinic with complaints of blood in his urine and weakness following an increase in his ketoconazole dose. Two days after presentation, the patient was admitted with rhabdomyolysis and acute renal failure, as evidenced by elevated serum creatine kinase (>32,000 IU/L), serum myoglobin (20.6 ng/mL), and serum creatinine (4.2 mg/dL) as well as abnormal bone scintigraphy findings. Ketoconazole, fenofibrate, and simvastatin were discontinued. Renal function did not normalize with hydration, and intermittent hemodialysis was initiated; 10 days of hemodialysis resulted in normalization of electrolytes and creatine kinase. Symptom improvement and normalization of laboratory parameters were observed after prolonged hospitalization (24 days). Discussion Prostate cancer is the most common malignancy among men in the US. Androgen deprivation therapy is the standard initial treatment for biochemical recurrence or metastatic disease. Most patients experience progression to a castrate-resistant disease state, requiring the use of additional therapies. Ketoconazole is considered a secondary hormonal treatment option. We describe an interaction in a patient with prostate cancer between a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor and ketoconazole resulting in rhabdomyolysis, requiring hemodialysis. An objective causality assessment using the Horn Drug Interaction Probability Scale revealed that the adverse drug reaction was a possible result of the interaction. Conclusions The temporal fashion in which the episode occurred suggests that a possible simvastatin-ketoconazole interaction precipitated rhabdomyolysis in this patient. The use of ketoconazole for castrate-resistant prostate cancer can lead to drug-drug interactions in patients taking simvastatin or other HMG-CoA reductase inhibitors. Clinicians should be aware of this severe adverse event and take steps to minimize its occurrence.

• To investigate the effect of combining gemcitabine plus capecitabine (GX) with bevacizumab (A) in patients with metastatic RCC previously treated with cytokines and targeted agents.• The combination of GX + A was evaluated in patients with metastatic RCC using institutional databases. • Data included demographics, previous therapies, number of metastatic sites, Memorial Sloan-Kettering Cancer Center risk stratification variables, and previous nephrectomy status. • Descriptive statistics and survival analysis were employed for data analysis.• Between January 2005 and October 2008, 28 patients were identified. Mean age was 55.7 years. Fifteen (53.57%) patients had been given tyrosine kinase inhibitor (TKI) previously. Nine (32.14%) patients had clear cell histology, 10 (35.71%) patients had sarcomatoid features on histopathology, and 19 patients (67.86%) had a prior nephrectomy. • Initial treatment consisted of G (mean dose 786.07 mg/m²) every 2 weeks, X (mean dose 2.73 g/day), and A (mean dose 10 mg/kg) every 2 weeks. Median progression-free survival (PFS) was 5.9 months and the median overall survival (OS) was 10.4 months. • In patients with previous TKI therapy, median PFS was 6.2 months and median OS was 11.7 months. • In patients with sarcomatoid features, median PFS was 3.9 months and OS was 9.0 months. • Three patients discontinued one or more of the drugs because of adverse reactions.• The combination of GX + A shows potential efficacy and acceptable tolerability in patients with intermediate and poor prognosis metastatic RCC. • Based on these observations, a phase II trial is now underway assessing this combination in patients with sarcomatoid RCC.

Candida lusitaniae, a Candida species frequently resistant to amphotericin B (AMB), is a rare cause of candidemia. The clinical significance of this in vitro resistant phenotype, the risk factors for, and the clinical presentation of C. lusitaniae fungemia in comparison with those of Candida albicans have not been completely characterized. We reviewed 13 consecutive cases of C. lusitaniae fungemia in cancer patients and compared them with 41 consecutive cases of C. albicans fungemia (1990-2004). The AMB mutational frequency and rate of fungicidal activity was compared between a bloodstream, AMB-susceptible C. lusitaniae isolate associated with clinical failure and reference C. albicans and Candida glabrata strains. In multivariate analysis, patients having C. lusitaniae fungemia were more likely to have neutropenia (p=0.001), stem cell transplantation (p=0.014) and to have received prior antifungals (p=0.04). Mutational frequencies at clinically-achievable AMB exposures were 8 x 10(5) for C. lusitaniae and

e16046 Background: Sipuleucel-T was the first cellular immunotherapy shown to prolong the life of patients with advanced prostate cancer. It was of interest to determine who were those patients mos...

528 Background: Bone metastases (BM) occur commonly in patients with metastatic renal cell carcinoma (mRCC). Tyrosine kinase inhibitors (TKIs) have improved outcomes for patients with mRCC. Data on outcomes of mRCC patients with BM treated with TKIs are limited, but suggest a worse outcome compared to non-BM groups. Herein, we describe outcomes of patients with BM treated with TKI therapy, and compare to outcomes in a pre-TKI control group. Methods: Retrospective review of patients with mRCC in the intervals of 2002-2003 and 2006-2007 was performed using the institutional tumor registry. Patient characteristics including demographics, laboratory data, and outcomes were analyzed. Overall survival (OS) was estimated using Kaplan-Meier methods. Predictors of OS were analyzed using Cox regression. Results: 375 patients were reviewed; 187 patients (50%) started treatment with TKIs and 188 patients (50%) started treatment in pre-TKI era. Distribution of patient characteristics was similar. Organ metastases were equally distributed, including BM in 48% of patients in each cohort. Median OS of patient treated with TKI therapy was 22 mo (95% CI: 17-25) compared to 14 mo (95% CI: 10-19; p

e15612 Background: Noninfectious pneumonitis (NIP) is a known adverse effect of mTOR inhibitors, with a reported incidence of 25-45%. The goal of this review was to characterize the incidence, onset, management, and clinical outcomes of pts with mRCC who experienced mTOR inhibitor-associated NIP at our tertiary cancer center. Methods: Retrospective review of 310 mRCC pts who received everolimus and/or temsirolimus between 6/1/2007 and 10/1/2010. Clinical correlation was made in conjunction with serial radiologic imaging studies. Results: 36 mRCC pts (12%) treated with an mTOR inhibitor developed NIP with a median time to symptom onset of 65 d (21-855) and radiographic appearance of 62.5 d (35-736). 23 pts (21%) received everolimus compared to 13 pts (6%) who received temsirolimus (P

e15611 Background: Sunitinib is a front-line therapy for metastatic renal cell cancer (mRCC). Recommended dose is 50 mg daily; 28 days (d) on/14 d off (traditional schedule; TS). Sunitinib is associated with several adverse events (AEs). An ideal treatment modification algorithm is not known. We sought to identify 1) common AEs, 2) alternative schedules (AS) that maintained dose intensity while decreasing AEs, and 3) the impact of AS on outcomes. Methods: Single-center retrospective review of mRCC pts performed from 1/26/06 to 3/1/11. Pts > 18 years of age with mRCC who received first-line antiangiogenic therapy with sunitinib were eligible. A subset of pts were switched at first intolerable AE from TS to a 14 d/7 d, or further adjusted to 7 d /3 d, or other AS. Control group underwent standard dose reduction. Pt characteristics including demographics, disease status, laboratory data, AEs, AS, and treatment outcomes were analyzed. Results: 186 eligible pts were identified. At baseline, 87% received sunitinib 50 mg and 88% were on TS. 99 pts (53%) continued TS and 87 pts (47%) were switched to AS. Baseline characteristics were similar. Median age was 61 yrs; by MSKCC criteria 5% were good, 50% intermediate, and 45% poor prognosis. Pts had median 2 visceral mets and 42% had primary tumor in place. AEs included fatigue (47%), diarrhea (24%), and hand-foot syndrome (26%). Median time to AS was 126 d with 14 d/7 d the most common (82%). Median time on treatment was 14.9 months (mo) (95% CI:10.2 – 17.0 mo) in AS pts vs 4.2 mo (95% CI: 3.6 – 5.7 mo), respectively (p < 0.0001). Median OS was 32.9 mo (95% CI:28.3-54.1 mo) vs 18.5 mo (95% CI: 10.3-21.5 mo), respectively (p = 0.0001). ECOG PS > 2 (HR 3.9), elevated LDH (HR 2.04), and > 2 mets (HR 1.79) were associated with decreased OS. MSKCC intermediate vs poor (HR 0.57) and AS (HR 0.54) were associated with improved OS by multivariate regression analysis (p < 0.05). Conclusions: In our cohort study, AS sunitinib significantly prolonged time on treatment and was predictive of OS. Prospective investigations of alternate dosing schemas are warranted.

367 Background: Pazopanib is an multi-tyrosine kinase inhibitor shown to prolong progression-free survival (PFS) compared to placebo in treatment-naive and cytokine-refractory mRCC. Outcomes and safety on its use after TT are limited. Methods: We retrospectively reviewed records of consecutive pts with mRCC who were treated with pazopanib between November 2009-November 2011 after having progressive disease (PD) with other TT. Radiographic response was assessed by a blinded radiologist using RECIST v1.1 criteria. PFS and overall survival (OS) were estimated by the Kaplan-Meier method. Hazard ratios (HR) were estimated by fitting univariable and multivariable Cox proportional hazards models to evaluate the association of PFS with patient co-variates. Results: 112 pts (median age 63 years, 67% male, 83% clear cell) met inclusion criteria. Median number of previous TT was 2 (range 1-5). 85 events (PD or death) occurred. 14 pts (12.5%) had a partial response. Median PFS was 5.7 months (95% CI: 4.3-8.9 months). PFS was significantly associated with male gender (HR=0.55; 95% CI: 0.34-0.87; p=0.011), clear-cell histology (HR=0.42; 95% CI: 0.24-0.74; p=0.0031), number of metastatic sites (HR= 1.26; 95% CI: 1.05-1.52; p=0.0123), pancreatic metastases (HR=0.40; 95% CI: 0.18-0.85;p=0.0185), Karnofsky PS< 80 (HR=2.07; 95% CI: 1.22-3.48; p=0.0062), and elevated LDH (HR=1.63; 95% CI: 1.03-2.573; p=0.035). Median OS was 16.9 months (95% CI: 10.3–21.9). 26% of pts were still receiving pazopanib at the time of analysis. 51% discontinued pazopanib due to PD and 12% died of PD on treatment. 11% discontinued pazopanib due to adverse events (AEs). There were no treatment related deaths. Common AEs included fatigue (43%), increase LFTs (34%), diarrhea (28%), nausea/vomiting (14%), anorexia (14%), hypertension exacerbation (12%), and hypothyroidism (11%). 89% of AEs were grade 1/2. Conclusions: Pazopanib demonstrated meaningful clinical activity in heavily pretreated pts with mRCC following PD with other TT. AEs were mild/moderate and manageable.

381 Background: Sunitinib is a front-line therapy for metastatic renal cell cancer (mRCC). Recommended dose is 50 mg daily; 28 days (d) on/14 d off (traditional schedule; TS). Sunitinib is associated with several adverse events (AEs). An ideal treatment modification algorithm is not known. We sought to identify (1) common AEs, (2) alternative schedules (AS) that maintained dose intensity while decreasing AEs, and (3) the impact of AS on outcomes. Methods: Single-center retrospective review of mRCC pts performed from January 26, 2006 to March 1, 2011. Pts > 18 years of age with mRCC who received first-line antiangiogenic therapy with sunitinib were eligible. A subset of pts were switched at first intolerable AE from TS to a 14 d/7 d, or further adjusted to 7 d /3 d, or other AS. Control group underwent standard dose reduction. Pt characteristics including demographics, disease status, laboratory data, AEs, AS, and treatment outcomes were analyzed. Results: 186 eligible pts were identified. At baseline, 87% received sunitinib 50 mg and 88% were on TS. 99 pts (53%) continued TS and 87 pts (47%) were switched to AS. Baseline characteristics were similar. Median age was 61 yrs; by MSKCC criteria 5% were good, 50% intermediate, and 45% poor prognosis. Pts had median 2 visceral mets and 42% had primary tumor in place. AEs included fatigue (47%), diarrhea (24%), and hand-foot syndrome (26%). Median time to AS was 126 d with 14 d/7 d the most common (82%). Median time on treatment was 14.9 months (mo) (95% CI:10.2 – 17.0 mo) in AS pts vs. 4.2 mo (95% CI: 3.6 – 5.7 mo), respectively (p < 0.0001). Median OS was 32.9 mo (95% CI:28.3-54.1 mo) vs. 18.5 mo (95% CI: 10.3-21.5 mo), respectively (p = 0.0001). ECOG PS > 2 (HR 3.9), elevated LDH (HR 2.04), and > 2 mets (HR 1.79) were associated with decreased OS. MSKCC intermediate vs. poor (HR 0.57) and AS (HR 0.54) were associated with improved OS by multivariate regression analysis (p < 0.05). Conclusions: In our cohort study, AS sunitinib significantly prolonged outcomes and was predictive of OS. Prospective investigations of alternate dosing schemas are warranted.

4615 Background: Pazopanib is an approved multi-tyrosine kinase inhibitor that prolongs progression-free survival (PFS) compared to placebo in treatment-naive and cytokine-refractory mRCC. Outcomes and safety data on its use after TT are limited. Methods: We retrospectively reviewed pts with mRCC who received salvage pazopanib between 11/09-11/11. Kaplan-Meier method was used to estimate survival outcomes. PFS was calculated from start of pazopanib until progressive disease (PD) or death. Univariable and multivariable Cox proportional hazards models were fitted to evaluate associations of PFS with covariables. Results: 114 consecutive pts met inclusion criteria (median age 62.6 years, 66% males, 83% clear cell). All pts had PD after other TT (median # of prior TT 2, range 1-5; median time on prior TT 23.3 mos). 79% of pts had PD on sunitinib, 39% on sorafenib, 19% on temsirolimus, 59% on everolimus, and 23% on bevacizumab. 25% received prior chemotherapy and 16% received prior cytokines in addition to TT. 87% had prior nephrectomy. 11% had favorable-risk, 68% intermediate-risk, and 21% poor-risk per MSKCC criteria. 85 events (PD or death) occurred. Median OS was 17 mos (95% CI: 10.3-NA). Median PFS was 6.4 mos (95% CI: 4.5-9.5). By multivariable analysis, PFS was associated with male gender (HR=0.433, 95%CI: 0.269-0.696; p=0.0006), # of metastatic sites (HR=1.252; 95%CI: 1.04-1.503; p=0.016), hypertension exacerbation (HR=0.378; CI: 0.175-0.813; p=0.0128) and PS 2+ vs.0-1 (HR=2.067; CI: 1.243-3.437; p=0.0052). 58% discontinued pazopanib due to PD, 12% died of PD on treatment, and 11% discontinued pazopanib due to adverse events (AEs), mostly GI complaints or fatigue. There were no treatment related deaths. Common AEs included: fatigue (44%), diarrhea (29%), nausea/vomiting (15%), anorexia (14%), hypertension exacerbation (11%), hypothyroidism (11%), hand-foot skin reaction (9%), and increase LFTs (4%). 86% of AEs were grade 1/2. Conclusions: In this retrospective study, pazopanib demonstrated efficacy in mRCC following PD with other TT. AEs were mild/moderate and manageable.

401 Background: P is a known adverse effect (AE) of mammalian target-of-rapamycin inhibitors, with a literature reported incidence of 25-45%. The goal of this review was to characterize the incidence, timing, management, and overall survival (OS) of pts treated at our center. Methods: Retrospective review of 332 patients (pts) with complete, evaluable records, who received E and/or T between 6/1/2007 and 10/1/2010. Clinical correlation was made in conjunction with serial radiologic imaging studies. Results: P occurred in 25.2 of E and 8.1 % of T pts. 10.7 of E and 11.1 % of T pts reported no symptoms (sx). 60.7 and 72.2 % reported cough, 67.9 and 61.1 % dyspnea, 17.9 and 5.6 % fever, and 67.9 and 88.9 % fatigue, with E and T, respectively. The median # of sx/pt was 2 and 3; 42.9 and 50 % received steroids, 35.7 and 22.2 % received antibiotics, 21.4 and 27.8 % had a pulmonary consult, and 10.7 and 16.7 % received oxygen, with E and T, respectively. Providers discontinued tx in 75 and 38.9%, continued tx in 17.9 and 27.8%, continued at reduced dose in 0 and 5.6%, held and later dose reduced in 7.1 and 16.7%, and held then resumed at same dose in 0 and 11.1% of pts, with E and T, respectively. The median NCI-CTC P grade was 2 (range 1–3) in both groups. No patients died from P. Conclusions: A higher incidence of P was observed in pts treated with E than T. The finding of improved OS in pts who develop P with E is intriguing and should be further investigated. [Table: see text]

431 Background: Non-RCC neoplasms of the kidney include neuroendocrine tumors (small cell carcinoma and carcinoid) and Primitive Neuroectodermal Tumors (PNET). Small cell carcinoma and renal carcinoids are small blue cell tumors that rarely occur as primary renal neoplasms. PNET, known as extraskeletal Ewing sarcoma, is characterized by t(11;22), the gold standard for diagnosis. It is a small round cell tumor derived from the neural crest and treated with chemotherapy; the role of nephrectomy is unclear. Methods: We reviewed records of patients seen at MDACC between 01/01/2001 and 01/01/2011 for PNET, small cell carcinomas, and carcinoid tumors of the kidney. Overall survival (OS) was determined from diagnosis to death. Results: 21 pts met inclusion criteria. Disease-specific data is shown in the table. Common treatments included: carboplatin/etoposide for small cell carcinomas; vincristine/doxorubicin/ifosfamide, vincristine/doxorubicin/cyclophosphamide, and doxorubicin/ifosfamide alternating with cisplatin/etoposide for PNET. Irinotecan was a common salvage agent in PNET. Most carcinoid tumors were treated with surgery alone. Two patients with small cell received whole brain radiation for brain metastases. Conclusions: Carcinoid tumors of the kidney had better outcomes compared to renal small cell carcinomas or PNET. Local carcinoid tumors of the kidney were generally managed with surgery alone. Renal small cell carcinomas and PNET were treated with systemic therapies. [Table: see text]

332 Background: Pneumonitis is a known adverse effect (AE) of mammalian target of rapamycin-inhibitors, with a literature reported incidence for everolimus ranging from 4 to 45%. The goal of this review was to characterize the incidence, timing, management, and outcomes related to everolimus-associated pneumonitis (EAP). Methods: Retrospective review of 86 mRCC patients (pts) with complete, evaluable records, given everolimus (E) between 4/2009 and 3/2010. We assessed baseline patient (pt) characteristics, previous therapies, time on E therapy, pt symptoms, physician management of AE, NCI-CTC pneumonitis grading, and survival outcomes. Radiologic CT indicated ground glass, inflammatory, and/or parenchymal opacities. Results: (See table.) EAP occurred in 28% of pts on E therapy, confirmed radiologically. 8% of EAP patients reported no symptoms. In EAP pts, 58% reported cough, 75% dyspnea and/or SOB, 17% fever, 71% fatigue. The median number of symptoms/patient was 3. 46% of pts received steroids (median 21 days (3-120)), 38% received antibiotics, 25% received pulmonary consultation, and 8% required oxygen. In pts who developed EAP, providers discontinued E in 75%, held and dose reduced E in 8%, and continued E in 17%. The median NCI-CTC pneumonitis grade was 2 (1-3); there were no treatment-related deaths. The median time to EAP onset was 67 days (8-442). There was no statistically significant difference in outcomes between EAP pts and non-EAP pts. Conclusions: EAP occurs often in mRCC pts treated with E. It is an important AE that can negatively affect pt symptoms, but did not adversely impact pt outcomes in our single-center experience. [Table: see text] [Table: see text]

e15115 Background: Sunitinib is a front-line therapy for metastatic renal cell cancer (mRCC). Recommended dose is 50 mg daily; 4 wk on, 2 wk off (4/2) schedule. Sunitinib is associated with several...

e15047 Background: Treatment of metastatic renal cell carcinoma (mRCC) includes antiangiogenic (AAG) therapy such as; sorafenib, sunitinib, and bevacizumab. Though better tolerated than historical ...

e16112 Background: Treatment of poor risk metastatic renal carcinoma (mRCC) is challenging, and empiric combinations may be attempted in practice once conventional therapies fail. These combinations may lead to formal clinical trials. Evaluation of mRCC patients given an empiric combination of gemcitabine (gem) capecitabine (cap), and bevacizumab (bev) at a tertiary care center was performed. Methods: After obtaining IRB approval, non investigational use of gem in combination with cap and bev in mRCC patients was identified using institutional databases. Collected data included demographics, previous therapies, number of metastatic sites, MSKCC risk stratification variables, prior nephrectomy status, drug therapy duration, and progression-free survival (PFS). Descriptive statistics were employed for data analysis. Results: Thirty-six patients were included in the analysis, with a median age of 55.5 years. Seventeen patients (47%) had previously received a tyrosine kinase inhibitor (TKI). Twenty-two patients (61%) had clear cell histology, 13 patients (36%) had sarcomatoid features, 20 patients (56%) had undergone previous nephrectomy, 20 patients (56%) had four or more sites of metastasis and 27 patients (75%) were diagnosed within 1 year of therapy. Initial treatment consisted of gem (908.61 mg/m2) every 2 weeks, cap (2.75 grams/day), and bev (828.82 mg) every 2 weeks. The median PFS for the study population was 5.83 months. The subset of TKI patients had a median PFS of 5.4 months. Therapy was relatively well tolerated with only 3 patients discontinuing one or more of the drugs due to adverse reactions. Thirteen of the patients started a TKI post discontinuation of the triple therapy. Conclusions: The triple therapy combination in this retrospective evaluation provides promising efficacy and acceptable tolerability in patients with poor prognosis mRCC. Based on these observations, a phase II is now underway assessing gemcitabine, capecitabine and becacizumab in patients with sarcomatoid RCC. [Table: see text]

e16110 Background: Sunitinib, an inhibitor of multiple tyrosine kinases, is FDA approved for metastatic renal cell cancer (mRCC). Though better tolerated than historical therapies, sunitinib is associated with adverse events (AEs) that may require dose modifications (DM). We sought to identify 1) baseline patient (pt) characteristics that predispose for DM, 2) the most common AEs requiring DM in a non-protocol setting, and 3) the impact of dose limiting AEs on treatment continuation. Methods: Single-center, retrospective chart review. Pts ≥ 18 years of age with mRCC of clear-cell histology on sunitinib therapy with active follow-up at MDACC were eligible. Univariate and multivariate logistic regression analysis of 66 pt variables (demographics, laboratory analysis, past medical and treatment history, etc) and dose-limiting AEs was completed, with a 6 month endpoint of sunitinib continuation, alternative therapy, or death. Results: From January 1, 2006 through September 30, 2007, 146 pts were identified meeting eligibility criteria. By univariate analysis, increased age (p=0.04; OR 1.04, 1.002–1.081 CI) and elevated BUN (p=0.03; OR 1.06, 1.006 –1.108 CI) were directly associated with increased incidence of dose-limiting AEs. ECOG PS of 2 (p=0.04; OR 0.3, 0.114–0.951 CI) was associated with a decreased incidence of dose limiting AEs. In a multivariate analysis, only BUN remained significant. 57% of patients (n= 83) had dose-limiting AEs. DM were often attributed to multiple AEs (55%), with fatigue, mucositis, hand-foot syndrome and nausea being the most common. At 6 months follow-up, 63% of pts with dose-limiting AEs remained on sunitinib vs. 37% (p=0.18). There was no difference in death rate at 6 months between the two groups. Conclusions: Elevated baseline BUN is associated with an increased rate of DM in patients with RCC receiving sunitinib. Despite the high-incidence of AEs, pts can be maintained on sunitinib with DM and without an adverse impact on outcome. Whether specific AEs are biologic indicators of activity should be evaluated in a larger clinical trial. [Table: see text]