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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.

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.

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.

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

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.

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