Effect of an individualized dose/schedule strategy for sunitinib in metastatic renal cell cancer (mRCC) on progression-free survival (PFS): Correlation with dynamic microbubble ultrasound (DCE-US) data.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 356-356 ◽  
Author(s):  
G. A. Bjarnason ◽  
B. Khalil ◽  
R. Williams ◽  
J. M. Hudson ◽  
B. Lloyd ◽  
...  
Keyword(s):  
Clear Cell ◽  
Cell Cancer ◽  
Prospective Trial ◽  
Area Under The Curve ◽  
Progression Free Survival ◽  
Dose Schedule ◽  
Pharmacokinetic Data ◽  
Free Survival ◽  
D 43

356 Background: Sunitinib area under the curve (AUC) correlates with response and PFS (Houk et al). Current recommendations for dose modification do not take this into account. Methods: A single center retrospective review identified mRCC patients (pts) where individualized (individ) sunitinib dose/schedule modifications (DSM) were used to maximize dose and minimize time off therapy (Rx). Pts were started on 50 mg 28 days (d) on/14 d off. DSM were done to keep toxicity (fatigue, skin, GI) at ≤ grade-2. DSM-1 was 50 mg 14 d/7 d with individ increases in d on Rx based on toxicity. DSM-2 was 50 mg 7 d/7 d with individ increases in d on Rx. DSM-3 was 37.5 mg continuously with individ 7 d breaks. DSM-4 was 25 mg continuously with individ 7 d breaks. Results: In 171 pts; median age was 60y; 20% good, 60% intermediate, 20% poor prognosis by Heng criteria; 80% had nephrectomy; 79% clear cell histology; 60% were previously untreated. At a median follow-up of 10.7 months (mo), overall median PFS was 7.9 mo. Of 39 pts still on therapy, 37 were on a DSM Rx. Pts were allocated to three groups based on the dose/schedule used for the longest time. The PFS/response% (PR+SD) for each group was 4.4 mo/65.6% (standard 50 mg 28 d/14 d; 43 pts), 8.0 mo/78.2% (DSM-1/DSM-2; 69 pts) and 10.4 mo/81.3% (DSM-3/DSM-4; 59 pts) with improved PFS (p=0.001) in both DSM groups vs. the standard schedule but no difference in response. 30 pts were studied by DCE-US at baseline, and after 7 d and 14 d on Rx or after 14 d and 28 d on Rx. In responding pts, tumor blood volume decreased at d 7 and again at d 14 vs. baseline but was stable or increased at d 28 vs. d 14. A rebound was seen after 14 d off Rx. Conclusions: Based on the U.S. data, previous pharmacokinetic data (steady state at 10-14 d) and this clinical data, starting pts on 50 mg 14 d/7 d followed by individ DSM may be safe and active. This DSM strategy, was associated with a favorable toxicity profile, apparent improvement in PFS and a good PR+SD rate in a group of unselected mRCC pts, warranting confirmation in a prospective trial. Pts that tolerate 50 mg 28 d/14 d with minimum toxicity may need dose escalation and/or less time off therapy to optimize PFS. [Table: see text]

scholarly journals High Expression of GSDMC Is Associated with Poor Survival in Kidney Clear Cell Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yun-Qian Cui ◽  
Fei Meng ◽  
Wen-Li Zhan ◽  
Zhou-Tong Dai ◽  
Xinghua Liao
Keyword(s):  
Potential Role ◽  
Clear Cell ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Renal Clear Cell Carcinoma ◽  
High Expression ◽  
Poor Survival ◽  
Free Survival

This study is aimed at exploring the potential role of GSDMC in kidney renal clear cell carcinoma (KIRC). We analyzed the expression of GSDMC in 33 types of cancers in TCGA database. The results showed that the expression of GSDMC was upregulated in most cancers. We found a significant association between high expression of GSDMC and shortened patient overall survival, progression-free survival, and disease-specific survival. In vitro experiments have shown that the expression of GSDMC was significantly elevated in KIRC cell lines. Moreover, decreased expression of GSDMC was significantly associated with decreased cell proliferation. In summary, we believe that this study provides valuable data supporting future clinical treatment.

Does endometriosis have an effect on the survival of women with synchronous endometrial and ovarian cancer?

2019 ◽  
Vol 11 (4) ◽  
pp. 185-193
Author(s):  
Engin Celik ◽  
Hale Goksever Celik ◽  
Hamdullah Sozen ◽  
Semen Onder ◽  
Merve Baktiroglu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Confidence Interval ◽  
Detrimental Effect ◽  
Clear Cell ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Free Survival ◽  
Pathological Characteristics

Purpose: Synchronous endometrial and ovarian cancer is defined as the concurrent presence of ovarian cancer with endometrial cancer. We aimed to evaluate whether there is an effect of endometriosis on progression-free survival and overall survival of women with synchronous endometrial and ovarian cancer. We also compared these findings with the patients having endometrial-only tumors and ovarian-only tumors. Methods: The patients who underwent surgery for endometrioid or clear-cell endometrial-only tumors and/or ovarian-only tumors and synchronous endometrial and ovarian cancer between 2005 and 2016 were included in this cohort study. The effect of the presence of endometriosis on progression-free survival and overall survival in these women who met the criteria was determined using statistical methods. Women were also compared regarding their demographic, clinical, and pathological characteristics. Results: A total of 176 patients were included in this study. All histology types of tumors located in endometrium or ovary were endometrioid or clear-cell cancer. Endometriosis was present in 62 patients (35.2%), whereas adenomyosis was present in 44 patients (25%). Endometriosis was diagnosed more frequently in women with ovarian-only tumors and synchronous endometrial and ovarian cancer than those with endometrial-only tumors (59.2% vs 5.7%, p < 0.001 and 45.7% vs 5.7%, p < 0.001, respectively). The patients with endometriosis showed no significantly longer progression-free survival and overall survival (hazard ratio = 1.70; 95% confidence interval = 0.48–6.03; p = 0.408 and hazard ratio = 1.67; 95% confidence interval = 0.30–9.44; p = 0.562, respectively). The presence of endometriosis was a stronger predictor for progression-free survival and overall survival comparing with the presence of adenomyosis. Conclusion: The women with synchronous endometrial and ovarian cancer should be informed that endometriosis has no detrimental effect on progression-free survival and overall survival.

Weekly cetuximab and paclitaxel combination in metastatic/recurrent squamous cell cancer carcinoma of the head and neck (SCCHN): Clinical experience of a single institution

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17043-e17043
Author(s):  
I. Diaz de Corcuera ◽  
C. Serrano ◽  
J. Pérez ◽  
I. Quispe ◽  
M. Arguis ◽  
...  
Keyword(s):  
Randomized Study ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Good Alternative ◽  
Phase Iii ◽  
Single Institution ◽  
Free Survival ◽  
Recent Phase ◽  
Unfit Patients

e17043 Background: Results of a recent phase III randomized study with cetuximab and platin-5FU chemotherapy support its use in recurrent/metastatic SCCHN. However, many patients (pts) are not able to be treated with platin combinations. Paclitaxel (P) and cetuximab (C) have shown an encouraging activity in a similar patients subset. We review the data of the patients treated with this schedule in our centre. Methods: From our database, we conducted a retrospective study of 20 patients with recurrent SCCHN who did not meet criteria for platin therapy and were treated with weekly P (80 mg/m2) and C (initially 400 mg/m2 followed by 250 mg/m2) until progression or intolerable toxicity. We have collected data regarding previous treatments, response rate (RR), progression free survival (PFS), overall survival (OS) and toxicity. Results: From January 2007 to November 2008, 20 patients were included (18 male, 2 female) with a median age of 63 (50–81). Oral cavity (35%) and oropharynx (25%) were the most frequent locations. Most of the pts (13/20) had been treated with previous chemotherapy combinations (range 1–3 lines). All pts were evaluable for response and toxicity. Overall RR was 45% (1CR, 8 PR) and 35% of the pts (7/10) had SD. Response in radiated areas were 35% (6/17). With a median follow up of 10 months the median PFS and OS were 6.5 and 7 months respectively. Main related toxicities (Gr 2/3) were acne-like rash (30%), asthenia (15%), anemia (10%), and mucositis (10%). Conclusions: Our analysis confirms that weekly paclitaxel-cetuximab is an effective and safety combination in metastatic/recurrent SCCHN. Treatment is very well tolerated and could be a good alternative to platin-based chemotherapy in unfit patients for this therapy. No significant financial relationships to disclose.

Six-year (yr) follow-up of patients (pts) with imatinib-resistant or -intolerant chronic-phase chronic myeloid leukemia (CML-CP) receiving dasatinib.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6506-6506 ◽  
Author(s):  
Neil P. Shah ◽  
Hagop Kantarjian ◽  
Dong-Wook Kim ◽  
Andreas Hochhaus ◽  
Giuseppe Saglio ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Advanced Disease ◽  
Chronic Phase ◽  
Progression Free Survival ◽  
Dose Schedule ◽  
Imatinib Resistance ◽  
Once Daily ◽  
Free Survival ◽  
Imatinib Resistant

6506 Background: Dasatinib, a potent BCR-ABL inhibitor, is approved for use as 1st- and 2nd-line therapy for CML pts with newly diagnosed disease or resistance/intolerance to imatinib. This ongoing study in pts with imatinib-resistant/-intolerant CML provides the longest follow-up of a second-generation BCR-ABL inhibitor. Methods: Study design has been described (Shah, J Clin Oncol 2008). Pts with imatinib-resistant/-intolerant CML (N=670) were randomized to dasatinib 100 mg once daily (QD), 50 mg twice daily (BID), 140 mg QD, or 70 mg BID. Results: Five-yr data are reported here; 6-yr data will be presented. After a minimum of 5 yrs, 151 pts (74%) remain on QD dosing, 85 of whom (56%) are on ≥100 mg QD dosing. Overall, 205 pts (31%) remain on study therapy with 55 pts (53%) originally randomized to BID dosing having switched to QD dosing. For pts randomized to the 100 mg QD arm (n=167), progression-free survival (PFS) at 5 yrs is 57%, overall survival (OS) is 78% with an overall 5% rate of transformation to advanced disease. In exploratory analyses, 42% and 60% of pts had BCR-ABL levels ≤10% (International Scale) at 1 and 3 months (mos), respectively. In a landmark analysis, BCR-ABL ≤10% at 1 or 3 mos was associated with higher 5-yr PFS. For dasatinib 100 mg QD, nonhematologic adverse events (AEs; all grades) generally first occurred in <24 mos. Cumulative rates of AEs in the 100 mg QD arm were headache (33%), diarrhea (28%), fatigue (26%), and pleural effusion (24%). For dasatinib 100 mg QD, cytopenias (grades 3/4) generally first occurred in <12 mos. The most common hematologic AEs (grades 3/4) in the 100 mg QD arm were neutropenia (36%) and thrombocytopenia (24%). AEs were managed by dose/schedule modifications. Conclusions: Five-yr follow-up of pts who switched to dasatinib 100 mg QD after imatinib-resistance/intolerance shows high rates of PFS, and OS with an overall low rate of transformation. Exploratory analyses suggest that achievement of a fast and deep response (≤10% BCR-ABL) at 1 or 3 mos after initiation of dasatinib 100 mg QD may be associated with a higher PFS. Dasatinib 100 mg QD was generally well tolerated over 5 yrs. Six-yr data will be presented.

Outcomes of patients with pancreatic-only oligometastatic renal cell carcinoma (RCC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 681-681
Author(s):  
Cassandra Duarte ◽  
Nieves Martinez Chanza ◽  
Katharine Collier ◽  
Nazli Dizman ◽  
Nityam Rathi ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Stereotactic Body Radiation Therapy ◽  
Clear Cell ◽  
Progression Free Survival ◽  
Tumor Characteristics ◽  
Comparative Efficacy ◽  
Rank Tests ◽  
Free Survival ◽  
Optimal Approach

681 Background: Patients (pts) with RCC and oligometastatic pancreas metastases are treated with pancreatectomy, stereotactic body radiation therapy (SBRT), or systemic therapy. The optimal approach is not clear. We aimed to evaluate the comparative efficacy of the modalities in terms of progression-free survival (PFS) and overall survival (OS). Methods: This IRB-approved, multi-institutional, retrospective study evaluated pts with pancreatic-only RCC metastasis without concurrent metastases elsewhere. Data on pt demographics, tumor characteristics, treatment, and outcomes were collected. PFS and OS in pts treated with pancreatectomy vs. systemic therapy were compared by log rank tests. Results: Fifty-one pts from 9 institutions were included. All had clear cell RCC; 50 pts had nephrectomy; 30 pts (58.8%) and 18 pts (35.3%) had IMDC favorable and intermediate risk, respectively. Median time from RCC diagnosis to oligometastatic disease was 120 months (mo) (range: 0, 175). As initial treatment, 23 (45%) pts had pancreatectomy (mostly partial); 25 (49%) had systemic therapy (VEGFR TKI and/or immunotherapy); 1 had SBRT; 2 had other treatments. Too few pts had SBRT for comparison. With a median follow-up of 25 mo (2, 68), median PFS for the population was 25 mo (17, 42 95% CI). Median PFS was 36 mo (8, 43 95% CI) for surgery pts and 22 mo (17, NR 95% CI) for systemic therapy pts; this was not statistically significant (NS), p = 0.3. Median OS for the population was 121 mo (100, NR 95% CI). With a median follow-up of 51 mo (2, 217), OS was 121 mo (100, NR 95% CI) for surgery pts and not reached (64, NR 95% CI) for systemic therapy pts; NS, p = 0.52. Conclusions: In this retrospective series, RCC pts with oligometastatic pancreatic-only disease had similar PFS and OS outcomes from initial pancreatectomy or systemic therapy. RCC pts with pancreas-only metastases represent a unique patient population and studies informing the underlying biology are needed to optimize clinical management.

Phase II study of hydroxyurea and gemcitabine in recurrent or persistent squamous cell cancer of the head and neck

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15524-15524
Author(s):  
S. Shibata ◽  
D. Lim ◽  
Y. Yen ◽  
M. Koczywas ◽  
R. Morgan ◽  
...  
Keyword(s):  
Head And Neck ◽  
Phase Ii ◽  
Squamous Cell ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Free Survival ◽  
Prior Chemotherapy ◽  
Wbc Count ◽  
Increased Activity

15524 Background: Preclinical studies demonstrate increased activity when hydroxyurea (HU) is given prior to gemcitabine (G). Clinical feasibility was demonstrated in a phase I trial (Yen, et. al. Cancer Chemother Pharmacol. 2002 ). We performed a phase II trial treating patients (pts) with squamous cell head and neck cancers (SCCHN). Methods: Pts had metastatic or incurable locally recurrent SCCHN. Prior chemotherapy was allowed, but not required. Serum creatinine ≤2.0 mg/dl, bilirubin <3.0 gm/dl, AST/ALT <5× ULN and KPS ≥60% were required. HU 500 mg orally every 6 hours for 4 doses was given on day 1 of a 21-day cycle. On day 2, 6 hours after HU, G 750 mg/m2 was given over 30 minutes. This sequence was repeated on day 8 and 9. After 8 pts, G was given at 500 mg/m2. G-CSF was given on day 10 and until the WBC count was >10k/μl. The primary endpoint was response rate (RR), with an early stopping rule for <3 objective responders among the first 18 pts. Results: 22 pts (17 M) were accrued, 16 with prior chemotherapy and 19 with prior radiation. The first 8 pts received G 750 mg/m2. Two pts died of neutropenic fever (NF) during course 1. Subsequently 14 pts received G 500 mg/m2. 18 pts were evaluable for response, with 1 still in follow-up. Partial response was seen in 1 pt, stable disease in 9, and progressive disease in 8. The overall median survival of the 22 pts was 6 months and the median progression free survival (PFS) was 2 months. The primary toxicity was hematologic. Grade 4 neutropenia was seen in 7/22 pts during the 1st cycle (5 at G 750 mg/m2) with 5 cases of NF. Grade 4 thrombocytopenia occurred in 1 pt at G 750 mg/m2. Conclusions: The RR and PFS of treated pts treated were not promising and further accrual is not planned. Analysis of biopsy materials is planned to see if responsive pts can be selected. (Supported by NCI Grant CA33572). No significant financial relationships to disclose.

Comparison of two dose calculation methods of intra-arterial carboplatin in the treatment of recurrent glioblastoma multiforme.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13503-e13503
Author(s):  
Brigitte Boilard ◽  
Alexandra Hinse ◽  
Karianne Beaulieu ◽  
Florence Marcotte ◽  
David Fortin ◽  
...  
Keyword(s):  
Prospective Trial ◽  
Area Under The Curve ◽  
Dose Calculation ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Hematologic Toxicity ◽  
Calculation Methods ◽  
Recurrent Glioblastoma Multiforme ◽  
Free Survival ◽  
The Impact

e13503 Background: Glioblastoma is a deadly brain cancer, and as part of the natural evolution, its relapses will mostly occur 32 to 36 weeks after the initial diagnosis. The standard of care for recurrent glioblastomas is not well defined and multiple options exist. Intra-arterial chemotherapy as one option is currently practiced at the Centre hospitalier universitaire de Sherbrooke, the only center doing this procedure in Canada. The aim of this study is to evaluate the impact of using the area under the curve (AUC) or body surface area (BSA) dosing formula to guide intra-arterial carboplatin administration. It was designed to explore the relation of two dose calculation methods on efficacy and toxicity, determined by progression-free survival (PFS) and hematologic toxicity, respectively. Methods: A retrospective observational study was conducted, which includes adult in-patients who received intra-arterial carboplatin for recurrent glioblastoma from June 1st, 2000 to December 31st, 2017. It examined the associations of the method used to calculate the doses, in mg or mg/mL x min-1, with clinical outcomes. Results: One hundred ninety patients were included in the analysis. For the primary endpoint, an exposure greater than 6 of AUC was found potentially harmful in terms of efficacy compared to AUC under 6 (HR 0.529, p = 0.0044). In terms of toxicity, a higher AUC is highlighted to correlate with a slightly higher incidence of thrombocytopenia and neutropenia (OR 1.051 p = 0.0271; OR 1.072 p = 0.049). No significant association between toxicity and dose calculated with BSA could be established. Conclusions: AUC greater than 6 is detrimental in terms of effectiveness according to progression free survival. Moreover, AUC could be used to predict neutropenia and thrombocytopenia. However no significant predictions were found using BSA method. We recommend the use of AUC method in intra-arterial carboplatin instead of BSA method since the latter was not statistically related to toxicity. A prospective trial comparing the two dosage methods would be needed.

Imatinib Is Effective in Children With Previously Untreated Chronic Myelogenous Leukemia in Early Chronic Phase: Results of the French National Phase IV Trial

2011 ◽  
Vol 29 (20) ◽  
pp. 2827-2832 ◽  
Author(s):  
Frédéric Millot ◽  
André Baruchel ◽  
Joelle Guilhot ◽  
Arnaud Petit ◽  
Thierry Leblanc ◽  
...  
Keyword(s):  
Prospective Trial ◽  
Chronic Phase ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Free Survival

Purpose Imatinib is the standard of care in adults with chronic myeloid leukemia (CML) in chronic phase (CP). Only a few studies to assess efficacy in children have been performed. We report on the results of the French prospective trial (ClinicalTrials.gov identifier NCT00845221) conducted in children and adolescents with newly diagnosed CML in CP. Patients and Methods A total of 44 patients from age 10 months to 17 years with newly diagnosed CML in CP received daily imatinib 260 mg/m2. Progression-free survival, responses, and tolerance were evaluated. Results With a median follow-up times of 31 months (range, 11 to 64 months), the estimated progression-free survival rate at 36 months was 98% (95% CI, 85% to 100%). A complete hematologic response was achieved in 98% of the patients. The rates of complete cytogenetic response (CCyR) and major molecular response (MMR) were 61% and 31% at 12 months, respectively. During follow-up, CCyR and MMR were achieved in 36 children (77%) and 25 children (57%), respectively. Overall, 30% of the patients discontinued imatinib, mainly because of unsatisfactory response. The most common adverse events were neutropenia and musculoskeletal events. Conclusion Imatinib is effective in children with CML in CP with response rates similar to rates reported in adults. The adverse effects are acceptable, but longer follow-up studies are required to fully assess the long-term impact.

Predictors of survival in non-metastatic renal cell cancer after surgery: A retrospective analysis

2019 ◽  
Vol 3 (2) ◽  
pp. 70-79
Author(s):  
Ines Zemni ◽  
Houyem Mansouri ◽  
Sabrine Haddad ◽  
Mohamed Ali Ayadi ◽  
Maher slimene ◽  
...  
Keyword(s):  
Renal Cell ◽  
Renal Carcinoma ◽  
Clear Cell ◽  
Cell Cancer ◽  
Disease Free Survival ◽  
Fuhrman Grade ◽  
Free Survival ◽  
Cell Renal Carcinoma ◽  
Disease Free

Aim: To investigate the prognostic significance of clinical and pathological factors of non-metastatic renal cell cancer after surgery. Patients and methods: We conducted a retrospective cohort study based on the records of patients with non-metastatic renal cancer submitted to radical or partial nephrectomy between 2000 and 2015 in Salah-Azaiez Institute. Results: Median follow-up was 38 months (interquartile range: 20–64). Five-year overall and disease-free survival were 53.8% and 43.1%. In the multivariate setting, lymph node invasion (p = 0.01), clear cell renal carcinoma subtype (p = 0.014), and tumor necrosis (p = 0.009) were the only independent statistically significant predictors of disease-free survival, while Fuhrman grade (p = 0.025), clear cell renal carcinoma subtype (p = 0.044), and TNM stage (0.041) were the only factors correlated with overall survival. Conclusion: For patients with non-metastatic renal cell carcinoma, independent predictors of disease-free survival and overall survival were clear cell renal cell carcinoma, Fuhrman grade, TNM stage, lymph node invasion, and tumor necrosis. Such information could be used to guide the intensity of follow-up and identify high-risk patients who can be targeted for adjuvant therapy trials.

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