Mayer Fishman

Moffitt Cancer Center, Tampa, Florida, United States

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Publications (65)379.42 Total impact

  • Robert Crescentini · Shilpa Gupta · Mayer Fishman

    No preview · Article · Jan 2016 · Translational Andrology and Urology
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    ABSTRACT: Fatigue is common among cancer patients and adversely impacts quality of life. As such, it is important to measure fatigue accurately in a way that is not burdensome to patients. The 7-item Patient Reported Outcome Measurement Information System (PROMIS) Cancer Fatigue Short Form scale was recently developed using item response theory (IRT). The current study evaluated the psychometric properties of this scale in two samples of cancer patients using classical test theory (CTT).
    No preview · Article · Dec 2015
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    ABSTRACT: Purpose: The purpose of the study is to examine changes in muscle strength and self-reported physical functioning in men receiving androgen deprivation therapy (ADT) for prostate cancer compared to matched controls. Methods: Prostate cancer patients scheduled to begin ADT (n = 62) were assessed within 20 days of starting ADT and 6 and 12 months later. Age and geographically matched prostate cancer controls treated with prostatectomy only (n = 86) were assessed at similar time intervals. Grip strength measured upper body strength, the Chair Rise Test measured lower body strength, and the SF-12 Physical Functioning scale measured self-reported physical functioning. Results: As expected, self-reported physical functioning and upper body muscle strength declined in ADT recipients but remained stable in prostate cancer controls. Contrary to expectations, lower body muscle strength remained stable in ADT recipients but improved in prostate cancer controls. Higher Gleason scores, more medical comorbidities, and less exercise at baseline predicted greater declines in physical functioning in ADT recipients. Conclusions: ADT is associated with declines in self-reported physical functioning and upper body muscle strength as well as worse lower body muscle strength relative to prostate cancer controls. These findings should be included in patient education regarding the risks and benefits of ADT. Findings also underscore the importance of conducting research on ways to prevent or reverse declines in physical functioning in this patient population.
    Full-text · Article · Nov 2015 · Supportive Care Cancer
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    ABSTRACT: Purpose: The 34-gene classifier, ClearCode34, identifies prognostically distinct molecular subtypes of clear cell renal cell carcinoma (ccRCC) termed clear cell A (ccA) and clear cell B (ccB). The primary objective of this study was to describe clinical characteristics and comorbidities of relevance in patients stratified by ClearCode34. Patients and methods: In this retrospective analysis, 282 patients from Moffitt Cancer Center with ccRCC with gene expression analyses of the primary tumor were identified and ClearCode34 was applied to identify tumors as ccA or ccB. The medical record and institutional databases were queried to define patient characteristics, comorbidities, and outcomes. Results: We validated in this external cohort the superior overall survival, cancer-specific survival, and recurrence-free survival of ccA patients relative to ccB patients (P<0.001). Addressing other clinical characteristics, the ccA patients were more likely to be obese (48% vs. 34%, P = 0.021) and diabetic (26% vs. 13%, P = 0.035). The ccA patients also trended toward having been more frequent users of angiotensin system inhibitors (71% vs. 52%, P = 0.055). In multivariate analyses, ccB status is independently associated with inferior cancer-specific survival (hazard ratio = 3.26, 95% confidence interval: 1.84-5.79) and overall survival (hazard ratio = 2.50, 95% confidence interval: 1.53-4.08). Conclusions: ClearCode34, after considering distinct patterns of comorbidities in each molecular subtype, remains a strong prognostic tool in patients with ccRCC. Obesity and diabetes mellitus emerged as factors that may influence ccRCC phenotypes and further studies investigating the effect of these metabolic conditions functionally onto tumor biology are warranted. Additionally, use of angiotensin system inhibitors could be studied in the context of ccRCC molecular classification in future studies to better understand its effect on ccRCC outcomes.
    No preview · Article · Nov 2015 · Urologic Oncology
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    ABSTRACT: We present our experience with minimally-invasive retroperitoneal lymph node dissection (MI-RPLND) in the post-chemotherapy (PC) setting for residual masses in patients with nonseminoma. Nineteen men who underwent PC MI-RPLND (14 - laparoscopic, 5 - robotic) for low-volume residual disease (no more than 5 clinically enlarged retroperitoneal masses, size < 5 cm, no adjacent organ or vascular invasion) between 2006 and 2011 were identified. Clinicodemographic information and pathological outcomes were reported. Median age of our study population was 32 (interquartile range [IQR]: 28-39). Most patients presented with clinical stage II disease (63%) and were categorized as good risk (90%) by the International Germ Cell Consensus Classification. Median size of residual masses on PC imaging was 2.1 cm (IQR: 1.7-3). Full-template bilateral RPLND was completed in 53% of cases, and modified left-sided RPLND in 47%. Median operative time was 370 minutes (IQR: 320-420), and median estimated blood loss was 300 cc (IQR: 150-450). Median length of stay was 3 days (IQR: 2-3). Five patients (26%) experienced a postoperative 30 day complication, but none were higher than Clavien grade II. On final pathology, median number of lymph nodes removed was 12 (IQR: 8-23), and 8 patients (42%) had residual teratoma. No patient experienced a recurrence at median follow up of 24 months (IQR: 5-76). PC MI-RPLND is a feasible option in a select group of patients with acceptable patient morbidity and short-term outcomes. Longer follow up is required to determine the oncologic efficacy of this approach.
    No preview · Article · Aug 2015 · The Canadian Journal of Urology
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    ABSTRACT: Background: Although UC is sensitive to platinum-based chemotherapy such as gemcitabine (G) + cisplatin (C), patients who are refractory to GC have limited therapeutic options. ALT-801 is an IL-2/single-chain T-cell receptor fusion protein previously tested in various murine models. ALT-801 demonstrated potent activity against syngeneic and xenograft UC, suggesting sensitivity of this disease to IL-2 based immunotherapy. Methods: We report efficacy and safety results of co-administration of G (1000 mg/m2/dose, d 1 & 8) + C (70 mg/m2/dose, d 1) with ALT-801 (0.06 mg/kg/dose, d3, 5, 8, 12) on a 21 day schedule for 3 cycles in patients with advanced/metastatic chemo-refractory UC. The initial ALT-801 dose escalation and expansion study included chemo-naïve or refractory subjects of group 1. Group 2 are patients in a 2-armed Phase II dose expansion study of only chemo-refractory subjects receiving either 0.06 mg/kg ALT-801 + GC or 0.06 mg/kg ALT-801 + G based on the renal function. Those with at least stable disease (SD) after 3 cycles may receive addition cycles of study treatment. Results: To date, 62 were enrolled of whom 34 were chemo-refractory receiving ALT-801+GC (group 1, n = 17; group 2, n = 17). They were 82% male, had median age 62 y (47-74); 47% were ECOG PS = 1, and 76% had visceral metastases. Favorable responses including complete response (CR) were seen in both groups 1 and 2 with an overall response rate of 35% (95% CI: 20 - 54%) (3 CR, 9 PR, 6 SD, 12 PD, 4 non-evaluable). Median OS was 12.3 months for group 1; the group 2 results are pending follow-up. Grade 3/4 toxicities observed (n = 31) include thrombocytopenia (62%), neutropenia (48%), anemia (39%), lymphopenia (26%), hypophosphatemia (19%) and low WBC (13%). Evaluation of treatment-induced immune responses is ongoing. Conclusions: Based on responses seen in both groups, we conclude that ALT-801+GC has clinical activity in advanced/metastatic chemo-refractory UC patients. Observed toxicities are consistent with GC and with ALT-801 known pharmacological effects. Further evaluation of this regimen in randomized trials is warranted. Clinical trial information: NCT01326871
    No preview · Conference Paper · Jun 2015
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    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.
    No preview · Article · May 2015 · Journal of Clinical Oncology
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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.
    Preview · Article · Apr 2015 · PLoS ONE
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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.
    Full-text · Conference Paper · Apr 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.
    No preview · Article · Mar 2015 · The Journal of urology
  • 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: Background: 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 and methods: 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 carried out; 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. Results: 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 mmHg groups had longer progression-free survival. Conclusions: 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.
    No preview · Article · Feb 2015 · Annals of Oncology

  • No preview · Article · Feb 2015 · Journal of Vascular and Interventional Radiology
  • 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.
    No preview · Chapter · Jan 2015
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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.
    No preview · Article · Dec 2014 · Clinical Genitourinary Cancer

  • No preview · Article · Oct 2014 · Cancer Research
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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.
    No preview · Article · Jun 2014 · Psycho-Oncology
  • 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.
    No preview · Article · Mar 2014 · Journal of immunotherapy (Hagerstown, Md.: 1997)
  • Neeraj Agarwal · Mayer Fishman
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    ABSTRACT: Interleukin-2 (IL-2) has been the mainstay of immunotherapy of metastatic renal cell carcinoma (mRCC) therapy for over 20 years. Although IL-2 treatment is limited to fit patients, a select group of these patients have derived substantial, durable benefit from it, for some translating into cures with no ongoing therapy or chronic toxicity. While targeted therapies are applicable to most patients, improvements of median survival have been measured in months. Immunotherapy, encompassing not only IL-2 but also newer checkpoint and vaccine approaches, therefore still has an important role for many as a main choice in RCC treatment. Enhanced patient selection techniques have evolved over time, and the overall response rate to high-dose (HD) IL-2 has improved among those selected patients. An increased understanding of immunotherapy has led to other novel approaches. These include checkpoint inhibitors mediating changes of T-cell behavior acting at the lymphocyte protein receptor programmed death-1 (PD-1), such as nivolumab, and vaccine immunotherapies, including peptide and dendritic cell vaccines in pivotal trials, and coordinated use of radiation therapy with IL-2, encouraging in early phase testing. Such approaches have the potential to expand the immune approach to achieve outcomes with better overall survival for many patients with mRCC.
    No preview · Article · Jan 2014
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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.
    Full-text · Article · Nov 2013 · Cancer Research
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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.
    Full-text · Article · Oct 2013 · The Lancet Oncology

Publication Stats

1k Citations
379.42 Total Impact Points

Institutions

  • 2002-2015
    • Moffitt Cancer Center
      • • Department of Biostatistics
      • • Department of Immunology
      Tampa, Florida, United States
  • 2001-2015
    • University of South Florida
      • Department of Oncologic Sciences
      Tampa, Florida, United States