Outcomes of patients with metastatic renal cell cancer treated with sunitinib in clinical practice at a reference cancer centre in Manchester, United Kingdom.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 477-477 ◽  
Author(s):  
Victoria Galvis ◽  
Dionne Lawrence ◽  
Matthew Howell ◽  
Fiona Thistlethwaite ◽  
Robert E. Hawkins
Keyword(s):  
United Kingdom ◽  
Clinical Practice ◽  
Detailed Analysis ◽  
Clinical Outcomes ◽  
Clear Cell ◽  
High Dose ◽  
First Line ◽  
Prognostic Features ◽  
Angiogenic Therapy ◽  
Clear Cell Rcc

477 Background: The development of anti-angiogenic therapy produced a change in the treatment of metastatic renal cancer (mRCC). There are now a range of drugs available with sunitinib being the most widely used first-line anti-angiogenic therapy. In the United Kingdom, until the advent of pazopanib it was the only such drug routinely funded by the NHS. The aim of this study was to audit the clinical outcomes of patients on routine treatment with sunitinib, to compare them with those obtained on trials and to analyze different subsets of patients. Methods: A database of mRCC patients treated at The Christie was set up to record clinical outcomes. Long-term follow-up data is available. Here we present a detailed analysis of 395 patients treated with sunitinib as a first-line anti-angiogenic therapy from 2005 to 2012. 397 patients treated out of a clinical trial. The outcomes were analysed according to various prognostic features. Results: The median OS of all patients audited was 18 months (m) with a PFS of 10.5m. This included clear cell RCC (n=305) and non-clear cell RCC (n=52). OS of clear cell RCC patients who received treatment second-line after cytokine therapy failure was 20.5m, longer than those treated first line 18.6m. This may be because we offer High-Dose IL2 to selected patients and these patients have a longer OS (24m) measured from the start of sunitinib. Baseline performance status was a predictor of outcome with OS being 23.5m for WHO PS 0/1 and 5.9m for WHO PS 2/3. Elderly age was not a predictor of poor outcome as the OS of patients <60, 60-70, and >70 was 15, 23, and 22m respectively. Time from nephrectomy to treatment with sunitinib had an influence on outcome with OS being 15, 24, and 48m for those <1, 1-5, and >5 years since nephrectomy. Further detailed analysis will be presented. Conclusions: Overall, the outcomes of patients treated in routine clinical practice were very similar to comparable groups treated on trials. Interestingly, the outcome post cytokine patients were particularly good but this may reflect particularly, careful choice of patients who receive cytokines since 2008.

scholarly journals TI-CE High-Dose Chemotherapy for Patients With Previously Treated Germ Cell Tumors: Results and Prognostic Factor Analysis

2010 ◽  
Vol 28 (10) ◽  
pp. 1706-1713 ◽  
Author(s):  
Darren R. Feldman ◽  
Joel Sheinfeld ◽  
Dean F. Bajorin ◽  
Patricia Fischer ◽  
Stefan Turkula ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Salvage Therapy ◽  
Primary Site ◽  
High Dose ◽  
First Line ◽  
Prognostic Features ◽  
Prior Therapy ◽  
Conventional Dose ◽  
Risk Patients ◽  
Disease Free

Purpose We previously reported a dose-finding and phase II trial of the TI-CE regimen (paclitaxel [T] plus ifosfamide [I] followed by high-dose carboplatin [C] plus etoposide [E] with stem-cell support) in germ cell tumor (GCT) patients predicted to have a poor prognosis with conventional-dose salvage therapy. We now report the efficacy of TI-CE with prognostic factors for disease-free survival (DFS) and overall survival (OS) in our full data set of 107 patients. Patients and Methods Eligible patients had advanced GCTs with progressive disease following chemotherapy and unfavorable prognostic features (extragonadal primary site, incomplete response [IR] to first-line therapy, or relapse/IR to ifosfamide-cisplatin–based conventional-dose salvage). Univariate and multivariate analyses (MVAs) of prognostic factors were performed. The predictive ability of the Einhorn and Beyer prognostic models was assessed. Results Most patients were platinum refractory and had an IR to first-line chemotherapy. There were 54 (5%) complete and eight (8%) partial responses with negative markers; 5-year DFS was 47% and OS was 52% (median follow-up, 61 months). No relapses occurred after 2 years. Five (24%) of 21 primary mediastinal nonseminomatous GCTs are continuously disease free. On MVA, primary mediastinal site (P < .001), two or more lines of prior therapy (P < .001), baseline human chorionic gonadotropin ≥ 1,000 U/L (P = .01), and lung metastases (P = .02) significantly predicted adverse DFS. Poor-risk patients did worse than good- or intermediate-risk patients according to both Beyer (P < .002) and Einhorn (P < .05) models. Conclusion TI-CE is effective salvage therapy for GCT patients with poor prognostic features. Mediastinal primary site and two or more lines of prior therapy were most predictive of adverse DFS. Beyer and Einhorn models can assist in predicting outcome.

First-line treatment with bevacizumab (B) and high dose (HD) bolus aldesleukin (IL-2) in metastatic renal cell carcinoma (mRCC) patients (Pts)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15524-15524
Author(s):  
M. S. Ernstoff ◽  
M. M. Regan ◽  
D. F. McDermott ◽  
J. A. Sosman ◽  
J. P. Dutcher ◽  
...  
Keyword(s):  
Clear Cell ◽  
Phase Ii Study ◽  
Prognostic Score ◽  
Thrombotic Event ◽  
Median Number ◽  
High Dose ◽  
Organ Function ◽  
First Line ◽  
Regulatory Pathways ◽  
Stimulation Of

15524 Background: The rationale for combining HD IL-2 with B includes potential synergistic immune interactions, non-overlapping toxicities, and potential for added clinical benefit. We have initiated a multi-center phase II study designed to estimate the efficacy of combination therapy of standard HD IL-2 and B therapy in mRCC pts. Methods: Pts with histologically confirmed mRCC, predominantly clear cell histology, measurable or evaluable disease, KPS of =80%, adequate end organ function for HD IL-2, and no underlying coagulopathy or thrombotic event are eligible for this study. One cycle consists of 84 days. B (10 mg/kg) IV is given every 2 wks beginning 2 wks prior to the first dose of IL-2. B is dosed 1 hr prior to initiating IL-2 on days IL-2 is given. HD IL-2 (600,000 IU/kg) IV Q8 hours (maximum 28 doses) is given during two 5-day courses separated by 9 days (starting on day 15 and 29). Results: We report the results of the first 15 of a planned 60 pts. The median age is 54 (range 40–73) with 9 men and 6 women. 14 pts have a MSKCC intermediate prognostic score, one pt has a poor prognostic score. In the first cycle, the median number of B doses was 7 of a planned 7 (range 2–7) and the median number of IL-2 doses was 17 of a planned 28 (range 6–26). There has been one treatment related death from unresponsive hypotension which occurred during the second cycle. Typical IL-2 toxicities have been noted thus far. Among a variety of correlative studies, we evaluated the serum L- ornithine (L-O) level, a byproduct of arginase-mediated arginine metabolism that has been shown to inversely correlate with TCR? chain expression. L-O level are significantly elevated in RCC pts possibly due to VEGF stimulation of arginase production. In 4 patients tested to date, peripheral blood L-O levels have dramatically decreased over the course of therapy. Conclusions: HD IL-2 and B can be given safely and may impact on immune regulatory pathways. [Table: see text]

Management of Advanced Germ Cell Cancer in Patients With Unfavorable Prognosis

2005 ◽  
Vol 3 (1) ◽  
pp. 77-83
Author(s):  
Kim Margolin
Keyword(s):  
Germ Cell ◽  
Cell Cancer ◽  
Germ Cell Cancer ◽  
Phase Iii ◽  
High Dose ◽  
Inadequate Response ◽  
Cell Transplant ◽  
First Line ◽  
Prognostic Features ◽  
Line Therapy

Advanced germ cell cancer can be cured in most patients using chemotherapy with or without surgery. A small fraction of patients with nonseminomatous tumors (NSGCT) and an even smaller percentage of seminoma patients are destined to have a less favorable outcome, due to an inadequate response to first-line chemotherapy (failure to achieve remission, finding of residual viable carcinoma at post-chemotherapy surgery, or relapse after achieving a remission). Despite the apparent salvage potential for regimens containing ifosfamide or paclitaxel, no proof exists that such combinations are superior to the standard regimen of four cycles of cisplatin, etoposide, and bleomycin (PEB) in the front-line therapy of patients with advanced NSGCT. Other modifications of first-line therapy, such as the addition of paclitaxel or the use of escalated doses of cisplatin, also have failed to increase the cure rate. The use of single or tandem cycles of high-dose chemotherapy (HDT with autologous hematopoietic cell transplant [aHCT]) in various settings (for selected patients with poor prognostic features before therapy, patients predicted to have a poor outcome based on the rate of serum tumor marker decline while on therapy, and patients in relapse or failure to achieve adequate response to standard therapy) has been evaluated in many phase II and a limited number of phase III trials, which are summarized in this review. Important questions that remain to be answered include the role of new agents and the use of more sophisticated techniques to understand prognostic and predictive factors in selecting therapy for GCT.

scholarly journals Racial Differences in Clinical Outcomes for Metastatic Renal Cell Carcinoma Patients Treated With Immune-Checkpoint Blockade

2021 ◽  
Vol 11 ◽  
Author(s):  
T. Anders Olsen ◽  
Dylan J. Martini ◽  
Subir Goyal ◽  
Yuan Liu ◽  
Sean T. Evans ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Clinical Outcomes ◽  
Metastatic Renal Cell Carcinoma ◽  
Real World ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Clear Cell ◽  
Caucasian Patients ◽  
Clear Cell Rcc

BackgroundImmune-checkpoint-inhibitors (ICIs) have become the cornerstone of metastatic renal-cell-carcinoma (mRCC) therapy. However, data are limited regarding clinical outcomes by race. In this study, we compared the real-world outcomes between African American (AA) and Caucasian mRCC patients treated with ICIs.MethodsWe performed a retrospective study of 198 patients with mRCC who received ICI at the Emory Winship Cancer Institute from 2015-2020. Clinical outcomes were measured by overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) defined as a complete or partial response maintained for at least 6 months per response evaluation criteria in solid tumors version 1.1. Univariate and multivariable analyses were carried out for OS and PFS by Cox proportional-hazard model and ORR by logistical-regression model. Descriptive statistics compared rates of immune-related adverse events (irAEs) and non-clear-cell-RCC (nccRCC) histology were assessed using Chi-square test.ResultsOur cohort was comprised of 38 AA and 160 Caucasian patients. Most were diagnosed with clear-cell-RCC (ccRCC) (78%) and more than half received (57%) PD-1/PD-L1 monotherapy. Most patients were intermediate or poor-risk groups (83%). Comparing to Caucasians, our AA cohort contained more females and nccRCC cases. Kaplan-Meier method showed AAs had no statistically different median OS (17 vs 25 months, p=0.368) and PFS (3.1 vs 4.4 months, p=0.068) relative to Caucasian patients. On multivariable analysis, AA patients had significantly shorter PFS (HR=1.52, 95% CI: 1.01-2.3, p=0.045), similar ORR (OR=1.04, 95% CI: 0.42-2.57, p=0.936) and comparable OS (HR=1.09, 95% CI: 0.61-1.95, p=0.778) relative to Caucasians.ConclusionsOur real-world analysis of ICI-treated mRCC patients showed that AAs experienced shorter PFS but similar OS relative to Caucasians. This similarity in survival outcomes is reassuring for the use of ICI amongst real-world patient populations, however, the difference in treatment response is poorly represented in early outcomes data from clinical trials. Thus, the literature requires larger prospective studies to validate these findings.

Ten-year follow-up of patients (pts) with metastatic renal cell carcinoma (mRCC) treated with interferon alfa-2b (IFN) as first-line therapy: Results from a randomized trial.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 365-365 ◽  
Author(s):  
Henry Jacob Conter ◽  
Christopher G. Wood ◽  
Surena F. Matin ◽  
Pheroze Tamboli ◽  
Randall E. Millikan ◽  
...  
Keyword(s):  
Clear Cell ◽  
High Dose ◽  
Intermediate Risk ◽  
Targeted Agents ◽  
Front Line ◽  
Long Term Outcome ◽  
Line Therapy ◽  
Significant Difference ◽  
Clear Cell Rcc

365 Background: We previously reported on improved tolerability and maintained efficacy of low-dose IFN in pts with mRCC treated in the cytokine era (Tannir, et al. Cancer 2006). Although VEGFR targeted agents have supplanted cytokines for most pts, IFN, in combination with bevacizumab, is a standard front-line therapy for good-risk and intermediate-risk clear-cell RCC. Methods: Between March 2002 and December 2003, a total of 118 pts (59/arm) were randomized to receive IFN 0.5 million units (MU) twice/day [IFN1] or 5 MU/day [IFN5]. Patients who were progression-free and tolerating therapy well continued IFN for a total of 5 years. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), overall survival (OS), safety, and quality of life (QOL). Results of PFS, ORR, safety, and QOL were previously reported. We provide here updated OS and long-term outcome of complete responders (CR). Results: At 10 years of follow-up, >95% of participants have died. There was no significant difference in OS between the 2 arms (HR=1.32, 95% CI: 0.91-1.91), but favored IFN1 (median OS 2.1 years vs. 1.5 years, log-rank test p=0.14). Compared with IFN5, IFN1 was less toxic and was associated with better QOL. Two nephrectomised pts, 1 from each arm, 1 with multiple hepatic and lung metastases, and 1 with multiple lung and mediastinal metastases, performance status 1 and intermediate-risk clear-cell RCC, remain in unmaintained CR 10 years since starting IFN. Among pts who did not respond to IFN but remain alive, 1 patient received high-dose IL-2 and achieved durable CR; the other patient received multiple approved and investigational targeted agents sequentially. All responders to IFN had tumor regression as early as 8 wks, with PR or CR declared at 16 wks. Conclusions: IFN produces durable CRs and potential cure in about 2% of mRCC pts. Our data have implications for the front-line therapy of mRCC and suggest that IFN, like high-dose IL-2, can be discontinued after 16 wks, if a major response is not achieved. Our updated results are of interest, considering the paucity of durable CRs to VEGFR agents.

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