Mayer Fishman

Moffitt Cancer Center, Tampa, Florida, United States

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Publications (58)376.65 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose Men receiving androgen-deprivation therapy (ADT) for prostate cancer may be at risk for cognitive impairment; however, evidence is mixed in the existing literature. Our study examined the impact of ADT on impaired cognitive performance and explored potential demographic and genetic predictors of impaired performance. Patients and Methods Patients with prostate cancer were assessed before or within 21 days of starting ADT (n = 58) and 6 and 12 months later. Age- and education-matched patients with prostate cancer treated with prostatectomy only (n = 84) and men without prostate cancer (n = 88) were assessed at similar intervals. Participants provided baseline blood samples for genotyping. Mean-level cognitive performance was compared using mixed models; cognitive impairment was compared using generalized estimating equations. Results ADT recipients demonstrated higher rates of impaired cognitive performance over time relative to all controls (P = .01). Groups did not differ at baseline (P > .05); however, ADT recipients were more likely to demonstrate impaired performance within 6 and 12 months (P for both comparisons < .05). Baseline age, cognitive reserve, depressive symptoms, fatigue, and hot flash interference did not moderate the impact of ADT on impaired cognitive performance (P for all comparisons ≥ .09). In exploratory genetic analyses, GNB3 single-nucleotide polymorphism rs1047776 was associated with increased rates of impaired performance over time in the ADT group (P < .001). Conclusion Men treated with ADT were more likely to demonstrate impaired cognitive performance within 6 months after starting ADT relative to matched controls and to continue to do so within 12 months after starting ADT. If confirmed, findings may have implications for patient education regarding the risks and benefits of ADT.
    Journal of Clinical Oncology 05/2015; DOI:10.1200/JCO.2014.60.1963 · 18.43 Impact Factor
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    Mayer N Fishman · Jin Tomshine · William J Fulp · Pamela K Foreman
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    ABSTRACT: Sorafenib was FDA approved in 2005 for treatment of renal cell carcinoma (RCC) based on the results of the pivotal phase 3 clinical trial, TARGET (Treatment Approaches in Renal Cancer Global Evaluation Trial). Since that time, numerous clinical studies have been undertaken that substantially broaden our knowledge of the use of sorafenib for this indication. We systematically reviewed PubMed, Web of Science, Embase, Cochrane Library, and www.clinicaltrials.gov for prospective clinical studies using single agent sorafenib in RCC and published since 2005. Primary endpoints of interest were progression-free survival (PFS) and safety. PROSPERO International prospective register of systematic reviews #CRD42014010765. We identified 30 studies in which 2182 patients were treated with sorafenib, including 1575 patients who participated in randomized controlled phase 3 trials. In these trials, sorafenib was administered as first-, second- or third-line treatment. Heterogeneity among trial designs and reporting of data precluded statistical comparisons among trials or with TARGET. The PFS appeared shorter in second- vs. first-line treatment, consistent with the more advanced tumor status in the second-line setting. In some trials, incidences of grade 3/4 hypertension or hand-foot skin reaction (HFSR) were more than double that seen in TARGET (4% and 6%, respectively). These variances may be attributable to increased recognition of HFSR, or potentially differences in dose adjustments, that could be consequences of increased familiarity with sorafenib usage. Several small studies enrolled exclusively Asian patients. These studies reported notably longer PFS than was observed in TARGET. However, no obvious corresponding differences in disease control rate and overall survival were seen. Collectively, more recent experiences using sorafenib in RCC are consistent with results reported for TARGET with no marked changes of response endpoints or new safety signals observed.
    PLoS ONE 04/2015; 10(4):e0120877. DOI:10.1371/journal.pone.0120877 · 3.23 Impact Factor
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    ABSTRACT: Cytoreductive nephrectomy (CN) is a therapeutic consideration in patients with metastatic renal cell carcinoma (mRCC). We hypothesized that sarcopenia, a novel marker of nutritional status, is a predictor of survival after CN. Of 105 patients who underwent CN at our institution for mRCC, 93 had preoperative imaging available for analysis. Skeletal muscle index was calculated on axial images at the third lumbar vertebrae, and a threshold skeletal muscle index of<43cm(2)/m(2) in men with a body mass index (BMI)<25kg/m(2),<53cm(2)/m(2) in men with a BMI>25kg/m(2), and<41cm(2)/m(2) in women was used to classify patients as sarcopenic vs. nonsarcopenic. This classification was then retrospectively correlated with overall survival (OS). Overall, 27 patients (29.0%) had sarcopenia before surgery. Sarcopenic patients received neoadjuvant systemic therapy more often (P = 0.022), had lower BMI (P = 0.001), had a higher incidence of hypoalbuminemia before surgery (P = 0.035), received more blood transfusions perioperatively (P = 0.006) owing to lower preoperative hemoglobin levels (P = 0.001), and had longer length of stay after surgery (P = 0.02). Median OS in sarcopenic patients was 7 months (95% CI: 0.8-13.2) vs. 23 months (95% CI: 12.4-33.6) in nonsarcopenic patients. On multivariate analysis, sarcopenia was an independent predictor of OS (hazard ratio = 2.13, 95% CI: 1.15-3.92; P = 0.016) in addition to number of metastatic sites>2 (hazard ratio = 2.09, 95% CI: 1.24-3.53; P = 0.006). Sarcopenia can be an important prognostic factor associated with worse OS after CN for mRCC. Copyright © 2015 Elsevier Inc. All rights reserved.
    The Journal of Urology; 04/2015
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    ABSTRACT: Many men receiving androgen deprivation therapy (ADT) for prostate cancer experience hot flashes. This study aimed to describe the course of hot flash interference (HFI) over time in ADT recipients relative to matched prostate cancer and cancer-free controls, from before the start of ADT to 12 months later. We also examined demographic, clinical, and genetic predictors of the impact of ADT on hot flash interference. Three groups were examined: prostate cancer patients recruited before or within 21 days of starting ADT (n=60), age- and education-matched prostate cancer patients treated with prostatectomy only (n=83), and age- and education-matched men with no history of cancer (n=86). Participants provided blood samples and completed the Hot Flash Daily Interference Scale at baseline as well as 6 and 12 months later. ADT recipients reported increasing HFI over time relative to controls (p<.001). Group differences were evident at 6 and 12 months (ps<.001), with ADT recipients reporting greater HFI than controls. Several genetic polymorphisms were found to predict greater increases in HFI (ps<.01), including polymorphisms on genes associated with vasoconstriction, immune function, neurotransmission, and circadian rhythms. ADT recipients who were younger and had lower body mass index at baseline also exhibited greater increases in HFI over time (ps≤.01). This study, the first to prospectively examine HFI in ADT recipients, found that those with certain genetic polymorphisms, younger age, and lower BMI had greater increases in HFI over time relative to controls. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
    The Journal of urology 03/2015; DOI:10.1016/j.juro.2015.03.026 · 3.75 Impact Factor
  • B I Rini · B Melichar · M N Fishman · M Oya · Y K Pithavala · Y Chen · A H Bair · V Grünwald
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    ABSTRACT: In a randomized, double-blind phase II trial in patients with metastatic renal cell carcinoma (mRCC), axitinib versus placebo titration yielded a significantly higher objective response rate. We evaluated pharmacokinetic and blood pressure (BP) data from this study to elucidate relationships among axitinib exposure, BP change, and efficacy. Patients received axitinib 5 mg twice daily during a lead-in period. Patients who met dose-titration criteria were randomized 1:1 to stepwise dose increases with axitinib or placebo. Patients ineligible for randomization continued without dose increases. Serial 6-h and sparse pharmacokinetic sampling were performed; BP was measured at clinic visits and at home in all patients, and by 24-h ambulatory BP monitoring (ABPM) in a subset of patients. Area under the plasma concentration-time curve from 0 to 24 h throughout the course of treatment (AUCstudy) was higher in patients with complete or partial responses than those with stable or progressive disease in the axitinib-titration arm, but comparable between these groups in the placebo-titration and nonrandomized arms. In the overall population, AUCstudy and efficacy outcomes were not strongly correlated. Mean BP across the population was similar when measured in clinic, at home, or by 24-h ABPM. Weak correlations were observed between axitinib steady-state exposure and diastolic BP. When grouped by change in diastolic BP from baseline, patients in the ≥10 and ≥15 mm Hg groups had longer progression-free survival. Optimal axitinib exposure may differ among patients with mRCC. Pharmacokinetic or BP measurements cannot be used exclusively to guide axitinib dosing. Individualization of treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitors, including axitinib, is thus more complex than anticipated and cannot be limited to a single clinical factor. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    Annals of Oncology 02/2015; DOI:10.1093/annonc/mdv103 · 6.58 Impact Factor
  • Journal of Vascular and Interventional Radiology 02/2015; 26(2):S192-S193. DOI:10.1016/j.jvir.2014.12.514 · 2.15 Impact Factor
  • Mayer Fishman
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    ABSTRACT: Interferon-α and interleukin-2 are cytokine drugs that were dominant medical treatments of metastatic kidney cancer for a time. A fraction of patients had dramatically good results, but most did not. With the availability demonstrated, more frequent clinical impacts of vascular endothelial growth factor (VEGF) axis inhibitors, and mammalian targets of rapamycin (mTOR) axis drugs on survival, more patients have visible cancer impacts from medical therapy, and more patients are on treatments with the newer groups of drugs than with cytokines. However, the unmistakable durability of some responses remains as a distinguishing feature for immune-based treatments. Processes for categorizing tumors and for understanding what makes an immune treatment more likely to work continue to evolve. Notwithstanding the mechanistic elegance of using synthetic proteins that interact with specific receptors on leukocytes, the fundamental potential for durable and complete responses has maintained cytokine therapies as part of the discussion for strategies to combat kidney cancer. In this chapter, highlights of the clinical trials’ experiences with interferon and with interleukin-2 in their use for kidney cancer treatment are reviewed in detail, as well as some other variant therapies incorporating cytokines.
    Renal Cell Carcinoma, 01/2015: pages 441-467; , ISBN: 978-1-4939-1621-4
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    ABSTRACT: The objective of this study was to determine if the percentage of sarcomatoid differentiation (%Sarc) in renal cell carcinoma (RCC) can be used for prognostic risk stratification, because sarcomatoid RCC (sRCC) is an aggressive variant of kidney cancer. We performed a retrospective analysis of patients who underwent surgery for RCC at our institution between 1999 and 2012. Pathology slides for all sRCC cases were reexamined by a single pathologist and %Sarc was calculated. %Sarc was analyzed as a continuous variable and as a categorical variable at cut points of 5%, 10%, and 25%. Potential prognostic factors associated with overall survival (OS) were determined using the Cox regression model. OS curves were generated using Kaplan-Meier methods and survival differences compared using the log-rank test. One thousand three hundred seven consecutive cases of RCC were identified, of which 59 patients had sRCC (4.5%). As a continuous variable %Sarc was inversely associated with OS (P = .023). Predictors of survival on multivariable analysis included pathologic (p) T status, tumor size, clinical (c) M status and %Sarc at the 25% level. OS was most dependent on the presence of metastatic disease (4 months vs. 21.2 months; P = .001). In cM0 patients with locally advanced (≥ pT3) tumors, OS was significantly diminished in patients with > 25 %Sarc (P = .045). However, %Sarc did not influence OS in patients with cM1 disease. Patients with sRCC have a poor overall outcome as evidenced by high rates of recurrence and death, indicating the need for more effective systemic therapies. In nonmetastatic patients, the incorporation of %Sarc in predictive nomograms might further improve risk stratification. Copyright © 2014 Elsevier Inc. All rights reserved.
    Clinical Genitourinary Cancer 12/2014; 191(4). DOI:10.1016/j.clgc.2014.12.001 · 1.69 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):5305-5305. DOI:10.1158/1538-7445.AM2014-5305 · 9.28 Impact Factor
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    ABSTRACT: Objective Prostate cancer patients who receive androgen deprivation therapy (ADT) often experience many physical and psychological side effects. ADT may be associated with increased risk for depression, but the relationship between ADT and depression is not fully understood. This study used a longitudinal design to assess depressive symptomatology in patients receiving ADT compared with two groups of matched controls.Methods Participants were men initiating ADT treatment (ADT+ group; n = 61) and their matched controls: prostate cancer patients treated with radical prostatectomy (ADT− group; n = 61), and no-cancer controls (CA− group; n = 61). Depressive symptomatology was assessed using the Center for Epidemiological Studies Depression Scale at ADT initiation and again 6 months later. Differences in depressive symptomatology and rates of clinically significant depressive symptomatology were analyzed between groups at each time point and within groups over time.ResultsBetween baseline and follow-up, ADT+ participants demonstrated increased depressive symptomatology and increased rates of clinically significant depressive symptomatology (ps < 0.05). ADT+ participants also reported greater depressive symptomatology than both control groups at follow-up (ps < 0.001). Rates of clinically significant depressive symptomatology were higher in the ADT+ group than the ADT− and CA− groups at both time points (baseline: 28%, 5%, 12%; follow-up: 39%, 9%, 11%).Conclusions Findings support the hypothesis that ADT administration yields increases in depression and suggest that the mechanism behind ADT's association with depression should be explored and that prostate cancer patients treated with ADT should receive particular focus in depression screening and intervention.Copyright © 2014 John Wiley & Sons, Ltd.
    Psycho-Oncology 06/2014; 24(4). DOI:10.1002/pon.3608 · 4.04 Impact Factor
  • Jason Brayer · Mayer Fishman
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    ABSTRACT: Aldesleukin [interleukin-2 (IL-2)] induces durable complete responses in some kidney cancer and melanoma patients. Nivolumab is an investigational antibody drug targeting programmed death-1 (PD-1) as a treatment, demonstrating activity in multiple cancer types. An expanding complement of immunotherapeutics raises important issues regarding the best way to use them. There are issues beyond identifying an agent that provides the superior front-line response: when does one therapy potentiate another immune therapy? When is the capacity of immune response exhausted and an approach without immune mechanism the better therapy? In this case report, we present a patient with metastatic renal cell carcinoma with no tumor regression evident on a PD-1 blockade (given on an investigational trial), who then achieved near-complete response to bolus high-dose IL-2 therapy, maintaining a persistent response off therapy. This case emphasizes on the need to develop improved predictors of response to immune therapies, especially as they can be applied to optimize sequential immunotherapeutic modalities versus predict when to turn to alternative targeted agents in renal cell carcinoma, and is an example of efficacious IL-2 application as a second-line treatment.
    Journal of immunotherapy (Hagerstown, Md.: 1997) 03/2014; 37(3). DOI:10.1097/CJI.0000000000000024 · 3.35 Impact Factor
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    ABSTRACT: Functionally altered myeloid cells play an important role in immune suppression in cancer, in angiogenesis, and in tumor cells' invasion and metastases. Here, we report that inhibition of Notch signaling in hematopoietic progenitor cells (HPC), myeloid-derived suppressor cells (MDSC), and dendritic cells (DC) is directly involved in abnormal myeloid cell differentiation in cancer. Inhibition of Notch signaling was caused by the disruption of the interaction between Notch receptor and transcriptional repressor CSL, which is normally required for efficient transcription of target genes. This disruption was the result of serine phosphorylation of Notch. We demonstrated that increased activity of caseine kinase 2 (CK2) observed in HPC and in MDSC could be responsible for the phosphorylation of Notch and down-regulation of Notch signaling. Inhibition of CK2 by siRNA or by pharmacological inhibitor restored Notch signaling in myeloid cells and substantially improved their differentiation, both in vitro and in vivo. This study demonstrates a novel mechanism regulation of Notch signaling in cancer. This may suggest a new perspective for pharmacological regulation of differentiation of myeloid cells in cancer.
    Cancer Research 11/2013; 74(1). DOI:10.1158/0008-5472.CAN-13-1686 · 9.28 Impact Factor
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    ABSTRACT: Population pharmacokinetic data suggest axitinib plasma exposure correlates with efficacy in metastatic renal-cell carcinoma. Axitinib dose titration might optimise exposure and improve outcomes. We prospectively assessed the efficacy and safety of axitinib dose titration in previously untreated patients with metastatic renal-cell carcinoma. In this randomised, double-blind, multicentre, phase 2 study, patients were enrolled from 49 hospitals and outpatient clinics in the Czech Republic, Germany, Japan, Russia, Spain, and USA. Patients with treatment-naive metastatic renal-cell carcinoma received axitinib 5 mg twice daily during a 4 week lead-in period. Those patients with blood pressure 150/90 mm Hg or lower, no grade 3 or 4 treatment-related toxic effects, no dose reductions, and no more than two antihypertensive drugs for 2 consecutive weeks were stratified by Eastern Cooperative Oncology Group performance status (0 vs 1), and then randomly assigned (1:1) to either masked titration with axitinib to total twice daily doses of 7 mg, and then 10 mg, if tolerated, or placebo titration. Patients who did not meet these criteria continued without titration. The primary objective was comparison of the proportion of patients achieving an objective response between randomised groups. Safety analyses were based on all patients who received at least one dose of axitinib. This ongoing trial is registered with ClinicalTrials.gov, number NCT00835978. Between Sept 2, 2009, and Feb 28, 2011, we enrolled 213 patients, of whom 112 were randomly assigned to either the axitinib titration group (56 patients) or the placebo titration group (56 patients). 91 were not eligible for titration, and ten withdrew during the lead-in period. 30 patients (54%, 95% CI 40-67) in the axitinib titration group had an objective response, as did 19 patients (34%, 22-48]) in the placebo titration group (one-sided p=0·019). 54 (59%, 95% CI 49-70) of non-randomised patients achieved an objective response. Common grade 3 or worse, all-causality adverse events in treated patients were hypertension (ten [18%] of 56 in the axitinib titration group vs five [9%] of 56 in the placebo titration group vs 45 [49%] of 91 in the non-randomised group), diarrhoea (seven [13%] vs two [4%] vs eight [9%]), and decreased weight (four [7%] vs three [5%] vs six [7%]). One or more all-causality serious adverse events were reported in 15 (27%) patients in the axitinib titration group, 13 (23%) patients in the placebo titration group, and 35 (38%) non-randomised patients. The most common serious adverse events in all 213 patients were disease progression and dehydration (eight each [4%]), and diarrhoea, vomiting, pneumonia, and decreased appetite (four each [2%]). The greater proportion of patients in the axitinib titration group achieving an objective response supports the concept of individual axitinib dose titration in selected patients with metastatic renal-cell carcinoma. Axitinib shows clinical activity with a manageable safety profile in treatment-naive patients with this disease. Pfizer Inc.
    The Lancet Oncology 10/2013; 14(12). DOI:10.1016/S1470-2045(13)70464-9 · 24.73 Impact Factor
  • Mayer N Fishman
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    ABSTRACT: Therapy for metastatic kidney cancer is actively evolving, particularly in the results of registration drug trials that have led to the approval of vascular endothelial growth factor pathway drugs such as sorafenib, sunitinib, pazopanib, bevacizumab, and axitinib, with focus on patients with good- or intermediate-risk criteria and clear cell histology. Mammalian target of rapamycin (mTOR) drugs such as everolimus and temsirolimus pivotal trials emphasize experiences in the setting of prior treatment or high-risk features. Interferon and interleukin 2 also are part of the treatment algorithms. The results of pivotal trials and the underlying context for the development of a cogent, cohesive treatment plan for an individual are reviewed, touching on decision points such as nephrectomy, metastasectomy, and medical initiation and discontinuation time points. To the extent that these drug therapies are essential for achieving best outcomes for patients, these pivotal trial results and associated guidelines exist within a multidimensional, multidisciplinary context of many other disease features, comorbid features, and non-drug treatment decisions. Other dimensions include investigational targeted therapies, patient selection strategies, surgical strategies, and immunotherapies, some of which are in active development. Clinicians should work toward the best use of drug sequencing and selection strategies based on core data derived from prospective randomized trials. To address individual patient needs, they should also recognize and emphasize individualized goals, to the extent that these are different from issues that were directly addressed in the trials.
    Cancer control: journal of the Moffitt Cancer Center 07/2013; 20(3):222-32. · 2.66 Impact Factor
  • International Symposium on Supportive Care in Cancer, Berlin, Germany; 06/2013
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    ABSTRACT: BACKGROUND: Research has shown that self-directed stress management training improves mental well-being in patients undergoing chemotherapy. The present study extends this work by evaluating separate and combined effects of stress management training and home-based exercise. METHOD: Following assessment of mental and physical well-being, depression, anxiety, exercise, and stress reduction activity before chemotherapy started, patients were randomized to stress management training (SM), exercise (EX), combined stress management and exercise (SMEX), or usual care only (UCO). Outcomes were reassessed 6 and 12 weeks after chemotherapy started. Significance testing of group-by-time interactions in 286 patients who completed all assessments was used to evaluate intervention efficacy. RESULTS: Interaction effects for mental and physical well-being scores were not significant. Depression scores yielded a linear interaction comparing UCO and SMEX (p = 0.019), with decreases in SMEX but not UCO. Anxiety scores yielded a quadratic interaction comparing UCO and SMEX (p = 0.049), with trends for changes in SMEX but not UCO. Additional analyses yielded quadratic interactions for exercise activity comparing UCO and SMEX (p = 0.022), with positive changes in SMEX but not UCO, and for stress management activity comparing UCO and SM (p < 0.001) and UCO and SMEX (p = 0.013), with positive changes in SM and SMEX but not UCO. CONCLUSION: Only the combined intervention yielded effects on quality of life outcomes, and these were limited to anxiety and depression. These findings are consistent with evidence that only the combined intervention yielded increases in both exercise and stress management activity. Future research should investigate ways to augment this intervention to enhance its benefits. Copyright © 2012 John Wiley & Sons, Ltd.
    Psycho-Oncology 06/2013; 22(6). DOI:10.1002/pon.3122 · 4.04 Impact Factor
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    ABSTRACT: BACKGROUND: Tivozanib is a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, -2 and -3, with a long half-life. Tivozanib has demonstrated clinical activity and acceptable tolerability in renal cell carcinoma (RCC). This phase Ib study determined the recommended phase II dose (RP2D) and evaluated the safety and clinical activity of tivozanib plus temsirolimus, a mammalian target of rapamycin inhibitor. PATIENTS AND METHODS: Patients with advanced RCC were administered open-label tivozanib 0.5, 1.0 or 1.5mg/d orally (3weeks on/1week off) and temsirolimus 15 or 25mg/week intravenously in a 3+3 dose-escalation design and subsequent expansion cohort. RESULTS: Of 27 patients treated, 20 patients had received ⩾1 prior VEGF-targeted therapy. No dose-limiting toxicities occurred; the RP2D was determined to be tivozanib 1.5mg/d plus temsirolimus 25mg/week. Combination of tivozanib plus temsirolimus demonstrated acceptable tolerability and suggested no synergistic toxicity. The most common grade ⩾3 adverse events were fatigue and thrombocytopenia (15% each). One patient each required dose reduction of tivozanib or temsirolimus due to an adverse event. Confirmed partial responses and stable disease were achieved at 23% and 68%, respectively. Pharmacokinetic analyses may suggest lack of an interaction between tivozanib and temsirolimus. CONCLUSIONS: In this small phase Ib study, tivozanib and temsirolimus were safely combined at the fully recommended dose and schedule of both agents. The observed clinical activity and manageable toxicity profile of this combination warrant further exploration in patients with RCC.
    European journal of cancer (Oxford, England: 1990) 05/2013; DOI:10.1016/j.ejca.2013.04.019 · 4.82 Impact Factor
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    ABSTRACT: Two major populations of myeloid-derived suppressor cells (MDSCs), monocytic MDSCs (M-MDSCs) and polymorphonuclear MDSCs (PMN-MDSCs) regulate immune responses in cancer and other pathologic conditions. Under physiologic conditions, Ly6C(hi)Ly6G(-) inflammatory monocytes, which are the normal counterpart of M-MDSCs, differentiate into macrophages and dendritic cells. PMN-MDSCs are the predominant group of MDSCs that accumulates in cancer. Here we show that a large proportion of M-MDSCs in tumor-bearing mice acquired phenotypic, morphological and functional features of PMN-MDSCs. Acquisition of this phenotype, but not the functional attributes of PMN-MDSCs, was mediated by transcriptional silencing of the retinoblastoma gene through epigenetic modifications mediated by histone deacetylase 2 (HDAC-2). These data demonstrate a new regulatory mechanism of myeloid cells in cancer.
    Nature Immunology 01/2013; 14(3). DOI:10.1038/ni.2526 · 24.97 Impact Factor
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    ABSTRACT: Axitinib is a novel, oral, multitargeted tyrosine kinase inhibitor, which inhibits vascular endothelial growth factor receptors 1, 2, and 3 at subnanomolar concentrations in vitro. In the phase III clinical trial in patients with metastatic renal cell carcinoma, axitinib showed a high objective response rate, and significantly prolonged progression-free survival compared with sorafenib. Thus, it is the first drug that has proven the concept of sequencing tyrosine kinase inhibitors in second-line treatment in a phase III prospective randomized trial. Although generally well tolerated and associated with a low incidence of grade 3 or 4 toxicities, axitinib shows a distinct pattern of adverse events that require monitoring and management. The most common adverse events observed with axitinib include diarrhea, hypertension, fatigue, nausea, and vomiting. This article summarizes the most important adverse events observed and proposes recommendations for their monitoring, prevention, and treatment. The recommendations are based on the existing literature and discussion by an expert group of international physicians and nurses specialized in oncologic treatment of metastatic renal cell carcinoma, which gathered in July 2011 in London, UK. Proactive assessment and management of adverse events during axitinib therapy can minimize treatment interruptions and ensure optimal effect of treatment.
    American journal of clinical oncology 01/2013; 37(4). DOI:10.1097/COC.0b013e31827b45f9 · 2.61 Impact Factor
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    ABSTRACT: Sipuleucel-T is an autologous cellular immunotherapy approved by the US Food and Drug Administration for the treatment of asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. Its mechanism of action is based on stimulation of the patient's own immune system to target prostate cancer. Peripheral blood mononuclear cells, including antigen-presenting cells and T cells, are obtained from patients via leukapheresis and treated ex vivo with PA2024, a fusion protein consisting of prostatic acid phosphatase/granulocyte-macrophage colony-stimulating factor antigen. Data relating to the potential pharmacodynamic biomarkers associated with sipuleucel-T activity are reviewed, as well as considerations for patient selection and for sequencing sipuleucel-T with other prostate cancer treatments. Possible directions for future development are also discussed, including treatment of less advanced prostate cancer populations, combination treatment, and immune modulation. Data from three randomized, double-blind, placebo-controlled phase III clinical trials of sipuleucel-T in patients with metastatic castration-rresistant prostate cancer have shown improvement in overall survival vs control. Here, we review its developing role in prostate cancer therapy and future directions for development. There is potential to build on sipuleucel-T to further advance immunotherapy of prostate cancer.
    Cancer control: journal of the Moffitt Cancer Center 01/2013; 20(1):7-16. · 2.66 Impact Factor

Publication Stats

1k Citations
376.65 Total Impact Points

Institutions

  • 2004–2015
    • Moffitt Cancer Center
      • • Department of Health Outcomes and Behavior (HOB)
      • • Department of Immunology
      Tampa, Florida, United States
  • 2001–2014
    • University of South Florida
      • Department of Oncologic Sciences
      Tampa, Florida, United States
  • 2005–2006
    • Bristol-Myers Squibb
      New York, New York, United States