Showing papers by "Walter M. Stadler published in 2007"
TL;DR: As compared with placebo, treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal-cell carcinoma in whom previous therapy has failed; however, treatment is associated with increased toxic effects.
Abstract: Background We conducted a phase 3, randomized, double-blind, placebo-controlled trial of sorafenib, a multikinase inhibitor of tumor-cell proliferation and angiogenesis, in patients with advanced clear-cell renal-cell carcinoma. Methods From November 2003 to March 2005, we randomly assigned 903 patients with renal-cell carcinoma that was resistant to standard therapy to receive either continuous treatment with oral sorafenib (at a dose of 400 mg twice daily) or placebo; 451 patients received sorafenib and 452 received placebo. The primary end point was overall survival. A single planned analysis of progression-free survival in January 2005 showed a statistically significant benefit of sorafenib over placebo. Consequently, crossover was permitted from placebo to sorafenib, beginning in May 2005. Results At the January 2005 cutoff, the median progression-free survival was 5.5 months in the sorafenib group and 2.8 months in the placebo group (hazard ratio for disease progression in the sorafenib group, 0.44;...
4,592 citations
TL;DR: A brief, functionally based screening tool, the Vulnerable Elders Survey‐13 (VES‐13), is evaluated for identifying older patients with prostate cancer (PCa) with impairment in the oncology clinic setting.
Abstract: BACKGROUND.
Impairments in geriatric domains adversely affect health outcomes of the elderly. The Comprehensive Geriatric Assessment (CGA) is a key component of the treatment approach for older cancer patients, but it is time consuming. In this pilot study, the authors evaluated the validity of a brief, functionally based screening tool, the Vulnerable Elders Survey-13 (VES-13), for identifying older patients with prostate cancer (PCa) with impairment in the oncology clinic setting.
METHODS.
Patients with PCa aged ≥70 years who actively were receiving androgen ablation treatment and who were followed within the clinics at the University of Chicago were eligible. Patients self-completed the VES-13 and CGA instruments and repeated the VES-13 1 month later. Physical performance and cognitive assessments were administered by a research assistant.
RESULTS.
Of 50 participating patients, 50% were identified as impaired by the VES-13 (score ≥3). Sixty percent of patients scored as impaired on ≥2 tests within the CGA, exhibiting deficits in multiple domains. The reliability of the VES-13 (Pearson correlation coefficient) was 0.92. The cut-off score of 3 on the VES-13 had 72.7% sensitivity and 85.7% specificity for CGA deficits and was highly predictive for identifying impairment (area under the receiver operating characteristic curve, 0.90). Patients who had mean VES-13 scores ≥3 performed significantly worse on evaluations of activities of daily living (P = .001), physical performance (P = .002), comorbidity (P = .004), and cognitive impairment (P = .003).
CONCLUSIONS.
Functional and cognitive impairments are highly prevalent among older patients with PCa who receive androgen ablation in oncology clinics. The current results indicated that the brief VES-13 performed nearly as well as a conventional CGA in detecting geriatric impairment in this population. Cancer 2007. © 2007 American Cancer Society.
244 citations
TL;DR: The development of international guidelines for the treatment of patients with locally advanced bladder cancer with neoadjuvant and adjuvant chemotherapy are reported.
191 citations
TL;DR: Clinical trial designs that treat change in tumor size as a continuous variable rather than categorizing the changes are feasible, and by inclusion of a prospective control group they offer advantages over conventional single-arm trials.
Abstract: Background The primary objective of phase II cancer clinical trials is to determine whether a new regimen has sufficient activity to warrant further study, with activity generally defined as tumor shrinkage. However, oncology drug development has been limited by high rates of failure (lack of efficacy) in subsequent phase III testing. This high failure rate may reflect the process by which antineoplastic agents are usually evaluated in phase II trials, i.e., via single-arm studies in which the primary efficacy measure is the proportion of patients who achieve a complete or partial response to the treatment. This design may efficiently eliminate truly ineffective therapy but may not reliably indicate whether subsequent phase III testing is warranted. Methods We describe the design of a randomized phase II clinical trial of sorafenib in combination with erlotinib for the treatment of patients with non-small-cell lung cancer using change in tumor size, measured on a continuous scale, as the primary outcome variable. For the purpose of determining the sample size of the trial, we made assumptions as to the likely magnitude of treatment effect and the variability in tumor size changes based on data from four previous trials using these agents. Results The study design includes two different dosage arms and a placebo group with a total sample size of 150 patients and is powered to detect a modest reduction in the mean tumor size burden in the high-dose sorafenib arm compared with a slight increase in the placebo group. Conclusions Clinical trial designs that treat change in tumor size as a continuous variable rather than categorizing the changes are feasible, and by inclusion of a prospective control group they offer advantages over conventional single-arm trials.
171 citations
TL;DR: Final OS differences did not reach prespecified O’Brien-Fleming statistical boundaries and are reported.
Abstract: 5023 Background: Based on the significant PFS benefit of sorafenib (SOR) vs placebo (P) in a Phase III advanced RCC trial, P patients were unblinded and crossed over to SOR in May 2005. Final OS an...
135 citations
TL;DR: Evidence indicates that ADT may accelerate the development of frailty in vulnerable older men with prostate cancer, and this potential consequence of ADT should be considered carefully when initiating therapy in older patients with recurrent prostate cancer.
Abstract: The majority of men with prostate cancer are aged > or =65 years. Men, as they age, are more likely to suffer from impaired physical function. The standard treatment for recurrent prostate cancer is androgen-deprivation therapy (ADT). Well-established toxicities from ADT include lean weight loss or sarcopenia, muscle weakness, fatigue, and reduced activity levels. Frailty is a term from geriatrics that describes older individuals with limited physiologic reserve who are at significant risk for adverse outcomes, including falls, disability, hospitalization, and death. An increasingly accepted definition of frailty is a syndrome in which > or =3 of the following are present: unintentional (lean) weight loss > or =10 pounds in the past year, weakness (measured by grip strength), slow walking speed, self-reported exhaustion, and low physical activity. This clinical syndrome overlaps closely with the known toxicities of ADT. In addition, alterations in the inflammatory system, neuroendocrine system, and energy production are associated with this syndrome, as evidenced by biomarkers such as C-reactive protein, interleukin-6, and tumor necrosis factor-alpha. For this article, the authors reviewed the evidence for the effect of ADT on each of the 5 frailty components plus the identified biomarkers, and the evidence indicates that ADT may accelerate the development of frailty in vulnerable older men with prostate cancer. Given the association of frailty with important clinical outcomes such as hospitalization and death, this potential consequence of ADT should be considered carefully when initiating therapy in older patients with recurrent prostate cancer.
115 citations
TL;DR: In phase II trials in MM, GC on a 21-day (D) schedule has response rates of 16%–26% and median overall survival (OS) of 9.6–13 months (mo).
Abstract: 7526 Background: In phase II trials in MM, GC on a 21-day (D) schedule has response rates of 16%–26% and median overall survival (OS) of 9.6–13 months (mo). Since VEGF has a key role in MM biology,...
95 citations
TL;DR: A small number of patients have responded to sunitinib and sorafenib and AG is a potent inhibitor of PDGFR, indicating potential for use in combination with other therapies for advanced RCC.
Abstract: 5032 Background: Sunitinib and sorafenib, tyrosine kinase inhibitors (TKIs) of the VEGF and PDGF receptors (VEGFR, PDGFR), are FDA-approved treatments for advanced RCC. AG is a potent inhibitor of ...
80 citations
TL;DR: Simulations suggest that this method can provide a reliable estimate of the AIF for DCE‐MRI data with a moderate signal‐to‐noise ratio (SNR) and temporal resolution, and its performance increases significantly as the SNR and temporalresolution increase.
Abstract: A precise contrast agent (CA) arterial input function (AIF) is important for accurate quantitative analysis of dynamic contrast-enhanced (DCE)-MRI. This paper proposes a method to estimate the AIF using the dynamic data from multiple reference tissues, assuming that their AIFs have the same shape, with a possible difference in bolus arrival time. By minimizing a cost function, one can simultaneously estimate the parameters and underlying AIF of the reference tissues. The method is computationally efficient and the estimated AIF is smooth and can have higher temporal resolution than the original data. Simulations suggest that this method can provide a reliable estimate of the AIF for DCE-MRI data with a moderate signal-to-noise ratio (SNR) and temporal resolution, and its performance increases significantly as the SNR and temporal resolution increase. As demonstrated by its clinical application, sufficient reference tissues can be easily obtained from normal tissues and subregions segmented from a tumor region of interest (ROI), which suggests this method can be generally applied to cancer-based DCE-MRI studies to estimate the AIF. This method is applicable to general kinetic models in DCE-MRI, as well as other CE imaging modalities.
80 citations
TL;DR: One objective response and several PSA declines following the discontinuation of therapy for toxicity suggest that evidence of clinical efficacy may be delayed, and careful attention must be paid to the novel toxicities of this agent with prolonged dosing.
Abstract: To explore the pharmacokinetics and tolerability of AZD2171, an inhibitor of vascular endothelial growth factor receptors 1 and 2, in patients with hormone refractory prostate cancer. Twenty-six patients received oral daily dosing of AZD2171 at 1, 2.5, 5, 10, 20, 30 mg. The maximum tolerated dose (MTD) was defined as the dose below that at which ≥33% of patients experienced a dose-limiting toxicity (DLT) within 21 days of initiating therapy. Pharmacokinetic analysis was performed. DLTs occurred at the 30 mg dose and included grade 3 events in three patients: fatigue (n = 3) and muscle weakness (n = 2). The pharmacokinetic profile revealed an effective half-life of approximately 27 h. At steady state, the unbound drug concentration was 4.4 times above the concentration required to inhibit endothelial cell proliferation in vitro. Four patients experienced PSA reductions within 30 days following drug discontinuation (one on 2.5 mg, two on 20 mg and 1 on 30 mg). In two patients treated with 20 mg, post therapy PSA declines persisted for >17 months, despite a PSA increase on therapy. Resolution of adenopathy occurred in one patient persisting for >17 months. Plasma concentrations were maximum 2–8 h post dosing with an overall median value of 2 h. The dose of 20 mg daily was declared as the MTD. One objective response and several PSA declines following the discontinuation of therapy for toxicity suggest that evidence of clinical efficacy may be delayed. While further study is indicated, careful attention must be paid to the novel toxicities of this agent with prolonged dosing.
64 citations
TL;DR: The finding that higher MKK4 and MKK7 expression is associated with higher‐stage prostatic tumours underscores the dynamic regulation of these proteins during prostatic cancer progression and highlights an important role for the SAPK signalling cascade in prostatic neoplasia.
Abstract: Identification of the signalling cascades that are differentially activated during prostatic tumourigenesis is a crucial step in the search for future molecular targets in this disease. The stress-activated protein kinase (SAPK) signalling cascade culminates in the phosphorylation of the JNK and p38 mitogen-activated protein kinases (MAPKs). Recently, the upstream activators of these proteins, the MAPK kinases (MKKs), have been implicated as inhibitors of tumour progression in a variety of clinical and experimental tumour models. This study evaluates MKK4, MKK6 and MKK7 expression during prostate cancer progression in humans and in the transgenic adenocarcinoma of a mouse prostate (TRAMP) model of prostate tumourigenesis. Benign prostate, prostatic intraepithelial neoplasia (PIN) lesions and tumour tissues were collected from 37 TRAMP mice. Additionally, six tissue microarrays were constructed with tumours from a matched group of 102 men who underwent radical prostatectomy. Tissues from 20 patients with extensive high-grade prostatic intraepithelial neoplasia (HGPIN) were also analysed. For all samples, immunohistochemical staining for MKK4, MKK6 and MKK7 was scored in normal and neoplastic glands. Staining intensities of MKK4, MKK6 and MKK7 were significantly increased in HGPIN and prostate cancer compared to surrounding normal glands in both the TRAMP and human samples (p < 0.0001 for all markers). Increased levels of MKK4 or MKK7 correlated with higher pathological stage at prostatectomy (p = 0.01 and p = 0.04). Using multivariate analysis, there was no association between protein levels and time to biochemical recurrence in the human samples. The up-regulation of MKK4, MKK6 and MKK7 during prostate cancer progression in both TRAMP and human tissues highlights an important role for the SAPK signalling cascade in prostatic neoplasia. The finding that higher MKK4 and MKK7 expression is associated with higher-stage prostatic tumours underscores the dynamic regulation of these proteins during prostatic tumourigenesis.
TL;DR: The ras oncogene is mutated in about 90% of PC, leading to constitutive activation of the Ras-Raf-MAPK signal transduction pathway, and Sorafenib an inhibitor of B-raf, VEGFR2, and PDG...
Abstract: 4608 Background: The ras oncogene is mutated in about 90% of PC, leading to constitutive activation of the Ras-Raf-MAPK signal transduction pathway. Sorafenib an inhibitor of B-raf, VEGFR2, and PDG...
TL;DR: A randomized, placebo‐controlled study of treatment with zoledronic acid every 3’months in patients with hormone‐sensitive prostate cancer, both with and without bone metastases, to assess the effect on bone mineral density (BMD) and markers of bone turnover.
Abstract: OBJECTIVE To report a randomized, placebo-controlled study of treatment with zoledronic acid every 3 months in patients with hormone-sensitive prostate cancer, both with and without bone metastases, to assess the effect on bone mineral density (BMD) and markers of bone turnover. PATIENTS AND METHODS Eligible patients included those with prostate cancer and on androgen-deprivation therapy for <12 months. Patients received zoledronic acid 4 mg intravenously, or placebo, every 3 months for four treatments. BMD, urinary N-telopeptides of type I collagen (NTX), and serum bone alkaline phosphatase (BAP) were measured every 3 months. In all, 42 patients were randomized. RESULTS After excluding BMD data from sites of known metastases, patients receiving zoledronic acid had a relative increase in BMD compared with those receiving placebo, of 4.2% and 7.1% at the femoral neck and lumbar spine, respectively. NTX and BAP decreased significantly in patients receiving zoledronic acid. NTX and BAP levels were significantly higher at baseline in patients with bone metastases than in those without. CONCLUSIONS Treatment with zoledronic acid every 3 months preserved bone density and suppressed markers of bone turnover in patients with androgen-deprived prostate cancer, both with and without bone metastases.
TL;DR: An oncogenomic approach is described, based on integrative analysis of gene expression profiling data, that has the potential to open up new avenues of molecular research and may have significant diagnostic and therapeutic implications in kidney cancer.
Abstract: In this age of targeted therapy, identification of molecular pathways that are deregulated in cancer will not only elucidate underlying tumorigenic mechanisms, but may also help to determine the classes of drugs that are used for treatment. In kidney cancer, a spectrum of histological subtypes exists that are characterized both by distinct molecular signatures and increasingly by distinct molecular pathways that are deregulated in each subtype. For example, the VHL/hypoxia pathway is well-known to be deregulated in clear cell renal cell carcinoma (RCC) whereas in papillary RCC activation of the HGF/Met pathway has been implicated. Additional molecular pathways, many not yet identified, may also be involved in the development of the different histologic subtypes. Moreover, differences in pathway activation may reflect differences in tumor progression and response to treatment. In this article, we describe an oncogenomic approach, based on integrative analysis of gene expression profiling data. In this approach, gene expression data is used to identify both cytogenetic abnormalities and molecular pathways that are deregulated in RCC. Ideally, predicted pathway abnormalities can be linked to predicted cytogenetic abnormalities to identify likely candidate genes. Although further cellular and functional studies are warranted to validate the computational models, development of such models in RCC have the potential to open up new avenues of molecular research and may have significant diagnostic and therapeutic implications.
TL;DR: Objectives were to analyze the safety and efficacy (response by RECIST) of 400 mg bid SOR in a community-based setting and enrolled pts with advanced RCC not eligible for, or without access to, other SOR clinical trials.
Abstract: 5011 Background: A prior phase III trial (TARGETs) demonstrated that sorafenib (SOR) doubled median progression-free survival versus placebo in previously treated clear cell renal cell cancer (RCC)...
TL;DR: The lower HR observed after censoring placebo patients crossed over to sorafenib suggests a continued beneficial effect of sorafinib, the first novel, oral approved treatment for advanced RCC in more than a decade.
TL;DR: This study evaluated the safety and activity of sunitinib in mRCC patients previously treated with the VEGF-neutralizing antibody, bevacizumab, and levels of angiogenic biomarkers, including plasma VEGf and soluble VEGFR-3, were assessed for predictive significance with clinical response.
Abstract: 5035 Background: Sunitinib malate is an oral, multitargeted tyrosine kinase inhibitor with antiangiogenic and antitumor activity. This study evaluated the safety and activity of sunitinib in mRCC patients (pts) previously treated with the VEGF-neutralizing antibody, bevacizumab. Levels of angiogenic biomarkers, including plasma VEGF and soluble VEGFR-3 (sVEGFR-3), were assessed for predictive significance with clinical response. Methods: Pts were required to have mRCC with disease progression following bevacizumab- based therapy, measurable disease, ECOG performance status 0 or 1, and adequate organ function. Pts were treated with sunitinib 50 mg daily in 6-week cycles (4 weeks on, followed by 2 weeks off). The primary endpoint was objective response according to RECIST. Plasma VEGF and sVEGFR-3 levels were measured in pre-treatment samples and at multiple timepoints on study. Results: A total of 61 pts were enrolled. The objective partial response rate was 23% (95% CI: 13%, 36%); 35 pts (57%) demonstrate...
TL;DR: A phase III trial showed that sorafenib (SOR) doubled progression-free survival (PFS) in previously treated pts with clear cell RCC, and this open-label, nonrandomized trial in North America was designed to better assess PFS in NCC.
Abstract: 5036 Background: A phase III trial showed that sorafenib (SOR) doubled progression-free survival (PFS) in previously treated pts with clear cell RCC. Activity of SOR in pts with NCC RCC has not bee...
TL;DR: This phase II trial was designed to investigate the role of sunitinib as maintenance therapy in patients with advanced urothelial cancer and decrease progression rates in patients who have obtained stable disease or better after standard chemotherapy.
TL;DR: The ability of this design to “select” a cohort most likely to benefit and to rigorously evaluate the disease-stabilizing activity of an investigational agent provides multiple advantages.
Abstract: An increasing number of putative anticancer targets and drugs have been identified with many of these expected to be growth inhibitory. Clinical development of these agents in the phase II setting is challenging because tumor shrinkages, or at least tumor shrinkages that meet the standard definitions of objective response, are not expected. Time to progression end points are however problematic because expected times in the absence of therapy (the null hypothesis) cannot be predicted accurately, thus requiring trials to enroll a concurrent control group. Another problem is that the patient population that will benefit from a new drug remains poorly defined in early-phase development. The randomized discontinuation trial design addresses both of these issues. All patients are initially treated with the drug; patients with an objective response continue therapy; patients who do not progress or experience excess toxicity within a prespecified "run-in" period are then randomized to continuing or discontinuing therapy in a double-blind, placebo controlled manner. Despite certain limitations that need to be recognized, the ability of this design to "select" a cohort most likely to benefit and to rigorously evaluate the disease-stabilizing activity of an investigational agent provides multiple advantages.
TL;DR: Sorafenib (SOR) was demonstrated to be safe and effective in a phase III trial of previously treated RCC pts; however, pts with BM were excluded.
Abstract: 15506 Background: Sorafenib (SOR) was demonstrated to be safe and effective in a phase III trial of previously treated RCC pts; however, pts with BM were excluded. BM occur in 5–10% of RCC pts, and...
TL;DR: Ixabepilone administered at a dose of 40 mg/m2 every 21 days should not be advanced for further study in metastatic RCC, given previous results, however, other dosing schedules may be worthy of further investigation.
Abstract: Introduction Ixabepilone (BMS-247550) is a semi-synthetic analog of epothilone B that has been characterized as a microtubule stabilizing agent with a mechanism of action distinct from taxanes. Suggestion of activity in renal cell carcinoma (RCC) has been seen in early clinical studies.Methods Eligible patients had metastatic RCC as well as ECOG performance status 0-2 and normal organ function. Patients received ixabepilone at a dose of 40 mg/m2 intravenously over 3 hours every 21 days. There was no restriction on RCC histology or prior treatment type, but prior treatment with tubule inhibitors was not allowed. The primary endpoint was RECIST defined response and radiographic evaluations were performed every 3 cycles. Toxicity evaluations utilized CTCAE v3.0 and were performed every cycle. Using a Simon two-stage optimal design with α=0.1, β=0.1, a null hypothesized response rate of 0.05 and an alternative response rate of 0.2, an initial 12 patients were to be accrued with full accrual of 37 patients if ...
TL;DR: Safety and efficacy in the SOR expanded access program in North America for pts receiving prior BEV, and ineligibility for, or lack of access to, other SOR clinical trials, are described.
Abstract: 5041 Background: Sorafenib (SOR) is an oral multi-kinase inhibitor of tumor-cell angiogenesis and proliferation. Phase III (TARGETs) data have demonstrated prolonged progression-free survival in pts with advanced clear cell renal cell carcinoma (RCC) in whom prior therapy failed. Activity of SOR following treatment with BEV, an anti-vascular endothelial growth factor and antiangiogenic monoclonal antibody, has not been evaluated. Methods: A subset analysis was conducted to describe safety and efficacy in the SOR expanded access program in North America for pts receiving prior BEV. Inclusion criteria for this open-label, nonrandomized trial included advanced RCC; ineligibility for, or lack of access to, other SOR clinical trials; age =15 years; ECOG PS of 0–2; recovery from prior treatment; adequate prior treatment of brain metastases. Major exclusion criteria included life expectancy <2 months; active coronary artery disease, ischemia or hypertension; severe renal impairment requiring dialysis. Pts previo...
TL;DR: This is the 1st study to report activity of an HDAC inhibitor in HRPC, and Romidepsin was administered intravenously at 13mg/m2 on days 1, 8 and 15 of a 28-day schedule.
Abstract: 15507 Background: Romidepsin is a bicyclic depsipeptide that inhibits histone deacetylase (HDAC). Translocations fusing TMPRSS2 gene and ERG oncogenic factor is associated with elevated HDAC-1 expression. HDAC inhibition results in accumulation of hyperacetylated histone proteins resulting in G1 and G2/M arrest, differentiation of transformed cells and apoptosis. Romidepsin can also inhibit HSP90, ablating androgen receptor expression. This is the 1st study to report activity of an HDAC inhibitor in HRPC. Methods: Romidepsin was administered intravenously at 13mg/m2 on days 1, 8 and 15 of a 28-day schedule. A 2-stage design was used. Eligibility criteria included: no prior chemotherapy, metastatic disease, QTcB <470msec, Karnofsky PS =80. The primary endpoint was to determine rate of disease control (complete response [CR], partial response [PR], stable disease [SD] for 6 months). Secondary endpoints were PSA response rate (RR), time to PSA and objective disease progression, safety profile, effect on dise...
TL;DR: In the Robson system stage 1 tumours are confined to the renal capsule, and stage 4 tumours show spread to local contiguous organs, excluding the adrenal gland, or to distant sites (4b).
Abstract: In the Robson system stage 1 tumours are confined to the renal capsule. Stage 2 tumours extend through the renal capsule but do not breach Gerota’s fascia. Stage 3 shows local involvement, including the renal vein or inferior vena cava (IVC) in the case of 3a, the hilar lymph nodes in the case of 3b, or both vein and node involvement in 3c disease. Stage 4 tumours show spread to local contiguous organs (4a), excluding the adrenal gland, or to distant sites (4b). Although this system reflects the anatomical extent of disease and can be used to predict prognosis with some accuracy, it has also been shown to correlate poorly with prognosis [2]. For example, patients with stage 3a disease have similar survival to some patients with stage 1 or stage 2 disease.
TL;DR: Sorafenib (SOR) doubled median progression-free survival (PFS) versus placebo in a phase III study (TARGETs) for previously treated pts with clear cell renal cell carcinoma (RCC).
Abstract: 5096 Background: Sorafenib (SOR) doubled median progression-free survival (PFS) versus placebo in a phase III study (TARGETs) for previously treated pts with clear cell renal cell carcinoma (RCC). ...
TL;DR: This study is designed to accrue 29 pts without progression at 6 months by objective and biochemical measures, and if ≥ 7/29 pts are progression-free at 6 month, the drug will be recommended for further study.
Abstract: 5132 Background: Histone deacetylases (HDACs) are key regulators of histone acetylation status, which is critical to expression of genes implicated in the regulation of cell survival, proliferation, differentiation and apoptosis. Vorinostat is a potent oral HDAC inhibitor with anti-tumor activity in PC models and in phase I clinical trials. A phase II trial is assessing vorinostat in HRPC pts. Methods: Eligible pts had disease progression on 1 prior chemotherapy for HRPC, a PSA of ≥ 5ng/ml, and adequate organ function. Vorinostat was administered orally at 400 mg daily in 21-day cycles. Response was assessed every 12 weeks. The primary endpoint is proportion of pts without progression at 6 months by objective and biochemical measures. This study is designed to accrue 29 pts (80% power at the 5% significance level to distinguish between a rate of 10% vs 30%). If ≥ 7/29 pts are progression-free at 6 months, the drug will be recommended for further study. Secondary endpoints include safety, rate of PSA decli...
TL;DR: This trial was conducted to define VFL activity in platinum-refractory TCCU patients with poor performance status, prior pelvic irradiation, or renal impairment, and found VFL 320 mg/m2 IV infusion over 20 minutes was administered every 3 weeks if well tolerated.
Abstract: 15543 Background: Vinflunine (VFL) is a new microtubule inhibitor of the vinca alkaloid class with clinical activity in TCCU (S. Culine, BJC 2006). This trial was conducted to define VFL activity i...
TL;DR: The recent development of effective therapy for renal cancer is a fascinating story of successful translational research that encompasses fundamental studies of oncogenesis and hypoxia, preclinical investigations of antiangiogenic therapy, and the use of novel clinical trial designs.
Abstract: The recent development of effective therapy for renal cancer is a fascinating story of successful translational research that encompasses fundamental studies of oncogenesis and hypoxia, preclinical investigations of antiangiogenic therapy, and the use of novel clinical trial designs. In fact, no