90Y glass microspheres for the treatment of unresectable metastatic liver disease from chemotherapy-refractory gastrointestinal cancers: A pilot study.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 359-359
Author(s):  
Nicholas Fidelman ◽  
Robert Keith Kerlan ◽  
Randall A. Hawkins ◽  
Emily K. Bergsland ◽  
Robin Kate Kelley ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pilot Study ◽  
Disease Control ◽  
Objective Response ◽  
Progression Free Survival ◽  
Response Duration ◽  
Treatment Session ◽  
Glass Microspheres ◽  
Free Survival ◽  
Carcinoid Crisis

359 Background: This prospective single-institution pilot study was undertaken to document the feasibility, safety, and efficacy of treatment of liver-dominant metastatic gastrointestinal cancer using 90Y glass microspheres. Methods: Between June 2010 and November 2012, 30 adult patients (22 men, 8 women; median age 61 years) with metastatic chemotherapy-refractory unresectable colorectal (n=15), neuroendocrine (n=9), biliary tract (n=3), pancreas (n=2), and esophageal (n=1) carcinomas underwent 45 lobar or segmental administrations of 90Y glass microspheres. Data regarding clinical and laboratory adverse events (AE) were collected prospectively for 6 months after each treatment. Radiographic responses were evaluated using Response Evaluation Criteria in Solid Tumors, version 1.1. Time to maximum response, response duration, progression-free survival (hepatic and extrahepatic), and overall survival were measured. Results: Median target dose and activity were 111.6Gy and 2.5GBq per treatment session, respectively. All but 3 clinical AE were grade 1 or 2 in severity. The most frequent clinical AE were fatigue (83%), anorexia (50%), nausea (50%), abdominal pain (40%), vomiting (20%), fever (17%), and sweating (17%). Common metabolic and laboratory AE included hypoalbuminemia (50%), transaminitis (63%), and hyperbilirubinemia (27%). Serious AE included an unplanned hospital admission for carcinoid crisis, grade 3 vomiting, and grade 4 gastric ulcer. Patients with colorectal cancer had hepatic objective response rate (ORR) of 27% and a disease control rate (DCR) of 73%. Median progression-free and overall survival were 1.0 and 4.9 months, respectively. Patients with neuroendocrine tumors had hepatic ORR and DCR of 78% and 100%, respectively. Median progression-free survival was 18.5 months for this cohort. Conclusions: 90Y glass microspheres device has a favorable safety profile, and achieved prolonged disease control of hepatic tumor burden in a subset of patients, including all patients enrolled in the neuroendocrine cohort. Clinical trial information: NCT01290536.

Anthracycline-Containing Regimens for Treatment of Follicular Lymphoma In Adults: Systematic Review and Meta-Analysis.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2820-2820 ◽  
Author(s):  
Gilad Itchaki ◽  
Anat Gafter-Gvili ◽  
Meir Lahav ◽  
Pia Raanani ◽  
Liat Vidal ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Disease Control ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Response Duration ◽  
Aggressive Lymphoma ◽  
Transformation Rate ◽  
Free Survival ◽  
Significant Difference

Abstract Abstract 2820 Introduction: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma (NHL), yet there are no standard guidelines regarding the best chemotherapeutic regimens for its management. The most prevalent regimens, especially in advanced disease, incorporate anthracyclines. There is no proof, however, that they are superior to non-anthracycline containing regimens, or even to single agent therapy. Methods: Systematic review and meta-analysis of randomized controlled trials comparing anthracycline-containing regimens (ACR) to non-anthracycline containing chemotherapy (non-ACR) for adult patients with FL. Trials assessing rituximab or other immunotherapy were included only if the anthracycline was the only difference between study arms. A comprehensive search was conducted with no restrictions, until July 2010. Two reviewers appraised the quality of trials and extracted data. The primary outcome was overall survival. Time to event data was extracted and pooled hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Secondary outcomes included survival at 5 years, disease control defined as progression free survival (PFS) or response duration (RD), transformation rate to aggressive lymphoma, complete remission (CR), overall response (OR), and adverse events. Risk ratios (RR) for dichotomous outcomes were pooled using random effects model. Heterogeneity was assessed using the I2 measure of inconsistency. Results: We identified ten trials, conducted between the years 1974–2006 and randomizing 2422 adult patients. Nine trials included naïve patients; one included relapsed and refractory FL patients. Six trials compared between the same chemotherapeutic regimens, with the addition of anthracyclines in the intervention arm as the only difference. There was no statistically significant difference between ACR and non-ACR arms, regarding overall survival at the end of follow up or all cause mortality at five years (HR 0.97; 95% CI 0.76 – 1.23 and RR 0.94; 95% CI 0.76 – 1.17, respectively, I2=0% for both analyses). PFS and RD favored the ACR arm, with a HR of 0.69, 95% CI 0.51–0.91 for disease control, 3 studies, I2=11%. There was no significant difference with regard to CR and OR, but analyses were heterogeneous. In four out of the ten trials, different chemotherapeutic regimens were compared, and only one study-arm contained anthracyclines. Similar to the results obtained with the same regimens comparison, there was no benefit for ACR with regard to OS (HR 0.94; 95% CI 0.77 – 1.15) and mortality at five years (RR 0.98; 95% CI 0.84 – 1.16). Disease control was improved with ACR (HR 0.74; 95% CI 0.60–0.93). In all studies, there were no data regarding transformation rate to aggressive lymphoma. Toxicity data reported was insufficient for appropriate meta-analysis. Overall, ACR were more often associated with cytopenias, especially neutropenia, although the frequency of serious infections or death related to chemotherapy was similar to non-ACR. Also, alopecia and gastrointestinal side-effects, including nausea and vomiting, were more common with ACR. Cardiotoxicity was reported in five trials, and albeit rare, was associated with anthracycline use (RR 8.62; 95% CI 1.58 to 47.05). Conclusion: The use of anthracyclines in patients with FL has no demonstrable benefit on overall survival. However, ACR improve disease control, as measured by progression free survival and response duration with an increased risk for side effects, notably cardiotoxicity. Disclosures: Shpilberg: Roche: Consultancy, Honoraria.

Apatinib monotherapy for chemotherapy-refractory metastatic colorectal cancer: A multicenter, single-arm, prospective study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3527-3527 ◽  
Author(s):  
Fen Wang ◽  
Shubin Wang ◽  
Xia Yuan ◽  
Jun Jia ◽  
Xiaoxia Bi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Prospective Study ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Disease Control Rate ◽  
Free Survival

3527 Background: Apatinib is an oral highly-selective tyrosine kinase inhibitor (TKI) that blocks vascular endothelial growth factor receptor 2 (VEGFR-2). This exploratory study evaluated the efficacy and safety of apatinib monotherapy in patients with chemotherapy-refractory metastatic colorectal cancer. Methods: In this multicenter, single-arm, prospective study, 48 patients with metastatic colorectal cancer who had failed at least two lines standard chemotherapies including fluorouracil, oxaliplatin and irinotecan were recruited from 14 centers in Guangdong, China. Apatinib at a 500mg dose was administered daily continuously. Each cycle was 4 weeks (28 days). The primary endpoint was progression free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL) and toxicity. Results: A total of 48 patients was enrolled in the study from September 3, 2015 to June9, 2017. Four patients achieved a partial response, and 22 achieved stable disease, representing a response rate of 8.3% and a disease control rate of 60.4%. Median follow-up time was 10.3 months. Median progression-free survival (PFS) and overall survival (OS) of evaluable patients (n=41) were 4.7 months (95% confidence interval [CI] 3.7-5.9) and 9.7 months (95% CI 5.9-13.6). The most common grade 3 or 4 adverse events (AE) were hypertension (12.5%), hand-foot syndrome (10.4%), thrombocytopenia (10.4%), proteinuria (8.3%) and mucositis oral (6.3%). Conclusions: Apatinib monotherapy shows promising efficacy and manageable toxicities in patients with chemotherapy-refractory metastatic colorectal cancer. Further phase 3 trial is warranted. Clinical trial information: ChiCTR1900020503.

scholarly journals Evaluation of efficacy and toxicity of nivolumab combined with or without docetaxel in patients with advanced NSCLC

2021 ◽  
Author(s):  
Yang Wang ◽  
Jun Nie ◽  
Ling Dai ◽  
Weiheng Hu ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Advanced Nsclc ◽  
Objective Response ◽  
Progression Free Survival ◽  
Meaningful Improvement ◽  
Free Survival ◽  
Significant Difference ◽  
Grade 3 ◽  
Doublet Chemotherapy ◽  
Platinum Doublet

Abstract Background The combination of PD-1/PD-L1 inhibitor and chemotherapy has been clinically confirmed to be beneficial as the first-line treatment of patients with advanced NSCLC. This study aimed to assess the effect of nivolumab + docetaxel versus nivolumab monotherapy in patients with NSCLC after the failure of platinum doublet chemotherapy. Materials and methods The efficacy and toxicity of nivolumab + docetaxel combination therapy versus nivolumab monotherapy were compared in this retrospective study. Primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), overall survival (OS), and toxicity. Results Between November 2017 and December 2019, 77 patients were included in this study, with 58 patients in the nivolumab group and 19 in the nivolumab + docetaxel group. The median follow-up was 18 months, and the PFS was 8 months for patients receiving nivolumab + docetaxel and 2 months for those receiving nivolumab alone (p = 0.001), respectively. Nivolumab + docetaxel showed superior OS compared with nivolumab, with the median OS unreached versus 7 months (p = 0.011). Among patients without EGFR/ALK variation, compared to nivolumab monotherapy, nivolumab + docetaxel showed better PFS (p = 0.04) and OS (p  = 0.05). There was no significant difference in grade 3–4 adverse events (AEs) between the two groups (p = 0.253). Conclusions The combination of nivolumab and docetaxel demonstrated a meaningful improvement in progression-free survival and overall survival compared to nivolumab monotherapy, in patients with NSCLC after the failure of platinum doublet chemotherapy, irrespective of EGFR/ALK variation status.

Effects of adding necitumumab to first-line chemotherapy in patients with stage IV non-small-cell lung cancer: Meta-analysis

2019 ◽  
Vol 26 (6) ◽  
pp. 1331-1342
Author(s):  
Irena Ilic ◽  
Sandra Sipetic ◽  
Jovan Grujicic ◽  
Milena Ilic
Keyword(s):  
Overall Survival ◽  
Objective Response Rate ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Meta Analysis ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival

Introduction Almost half of patients with non-small-cell lung cancer (NSCLC) are diagnosed at an advanced stage. Our aim was to assess the effects of adding necitumumab to chemotherapy in patients with stage IV NSCLC. Material and methods A comprehensive literature search was performed according to pre-specified inclusion and exclusion criteria. Data on overall survival, progression-free survival, objective response rate and adverse events were extracted. A meta-analysis was performed to obtain pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) for time-to-event data and pooled odds ratio (OR) with 95% CI for dichotomous outcomes. Results The meta-analysis included four randomized clinical trials with 2074 patients. The pooled results showed significant improvement for overall survival (HR = 0.87 (95% CI 0.79–0.95), p = 0.004) when necitumumab was added to chemotherapy in patients with advanced NSCLC. No statistically significant improvement was noted for progression-free survival and objective response rate (HR = 0.83 (95% CI 0.69–1.01), p = 0.06 and OR = 1.46 (95% CI 0.90–2.38), p = 0.13, respectively). Subgroup analysis showed that in patients with non-squamous NSCLC, there was no benefit in overall survival and objective response rate. Patients with advanced NSCLC who received necitumumab were at the highest odds of developing a skin rash (OR = 14.50 (95% CI 3.16–66.43), p = 0.0006) and hypomagnesaemia (OR = 2.77 (95% CI 2.23–3.45), p < 0.00001), while the OR for any grade ≥3 adverse event was 1.55 (95% CI 1.28–1.87, p < 0.00001). Conclusions The addition of necitumumab to standard chemotherapy in a first-line setting in patients with stage IV NSCLC results in a statistically significant improvement in overall survival, while the results were not significant for progression-free survival and objective response rate.

Progression-Free Survival in Children With Optic Pathway Tumors: Dependence on Age and the Quality of the Response to Chemotherapy—Results of the First French Prospective Study for the French Society of Pediatric Oncology

2003 ◽  
Vol 21 (24) ◽  
pp. 4572-4578 ◽  
Author(s):  
Véronique Laithier ◽  
Jacques Grill ◽  
Marie-Cécile Le Deley ◽  
Marie-Madeleine Ruchoux ◽  
Dominique Couanet ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Disease Progression ◽  
Objective Response ◽  
Progression Free Survival ◽  
Optic Pathway ◽  
Free Survival ◽  
Factors Associated ◽  
Response To Chemotherapy ◽  
Risk Of Disease

Purpose: To evaluate a strategy aimed at avoiding radiotherapy during first-line treatment of children with progressive optic pathway tumors (OPT), by exclusively administering multiagent chemotherapy during 16 months. Patients and Methods: Between 1990 and 1998, 85 children with progressive OPT were enrolled onto this multicenter nationwide trial. Chemotherapy alternating procarbazine plus carboplatin, etoposide plus cisplatin, and vincristine plus cyclophosphamide was given every 3 weeks. At the time of relapse or progression, second-line chemotherapy was authorized before recourse to radiotherapy. Results: Objective response rate (partial response [PR] + complete response [CR]) to chemotherapy was 42%. Five-year progression-free survival (PFS) and overall survival rates were 34% and 89%, respectively. The 5-year radiotherapy-free survival rate was 61%. In the multivariate analysis of the 85 patients that entered onto the study, factors associated with the risk of disease progression were age younger than 1 year at diagnosis (P = .047) and absence of neurofibromatosis type 1 (P = .035). In the multivariate analysis of the 74 patients that remained on study after the first cycle of chemotherapy, factors associated with the risk of disease progression were age younger than 1 year at diagnosis (P = .0053) and no objective response to chemotherapy (P = .0029). Three-year PFS was 44% in infants ≤ 1 year versus 66% in children older than 1 year. Three-year PFS was 53% in the absence of an objective response to chemotherapy versus 68% after a PR or CR. Conclusion: A significant proportion of children with OPT can avoid radiotherapy after prolonged chemotherapy. Deferring irradiation with chemotherapy protocols did not compromise overall survival of the entire population or visual function.

scholarly journals TILs and Anti-PD1 Therapy: An Alternative Combination Therapy for PDL1 Negative Metastatic Cervical Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Huanhuan Yin ◽  
Wei Guo ◽  
Xiangling Sun ◽  
Ruili Li ◽  
Cuihua Feng ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Overall Survival ◽  
Combination Therapy ◽  
Survival Time ◽  
Response Rate ◽  
Multivariate Analyses ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Kaplan Meier

Background. We investigated the efficacy of TILs and anti-PD1 combination therapy in patients with metastatic cervical cancer with low MSI expression and PDL1-negative. Methods. A total of 80 patients were put on TILs and anti-PD1 combination therapy, and the progression-free survival time (PFS) and overall survival time (OS) were assessed by Kaplan–Meier analysis. Univariate and multivariate analyses were performed to identify factors that could predict the prognosis of metastatic cervical cancer in the previously described patients. Results. The objective response rate was 25%, whereas the mPFS and mOS were 6.1 and 11.3 months, respectively. The therapeutic efficacy was influenced by the characteristics of TILs, infection with HPV, and development of fever just after the therapy. Conclusion. Overall, our results show that the combination therapy of TILs and anti-PD1 significantly improves the prognosis of metastatic cervical cancer.

scholarly journals Randomized Open-Label Phase II Trial of Apitolisib (GDC-0980), a Novel Inhibitor of the PI3K/Mammalian Target of Rapamycin Pathway, Versus Everolimus in Patients With Metastatic Renal Cell Carcinoma

2016 ◽  
Vol 34 (14) ◽  
pp. 1660-1668 ◽  
Author(s):  
Thomas Powles ◽  
Mark R. Lackner ◽  
Stéphane Oudard ◽  
Bernard Escudier ◽  
Christy Ralph ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Adverse Events ◽  
Renal Cell ◽  
Response Rate ◽  
Objective Response ◽  
Mammalian Target Of Rapamycin ◽  
Hypoxia Inducible Factor ◽  
Progression Free Survival ◽  
Free Survival

Purpose To the best of our knowledge, this study is the first to compare dual inhibition of PI3K/mammalian target of rapamycin (mTOR) by apitolisib (GDC-0980) against single inhibition of mTORC1 by everolimus in metastatic renal cell carcinoma (mRCC). Patients and Methods Patients with clear-cell mRCC who progressed on or after vascular endothelial growth factor–targeted therapy were randomly assigned to apitolisib 40 mg once per day or to everolimus 10 mg once per day. End points included progression-free survival, safety, overall survival, and objective response rate. Biomarker assessments were conducted. Results Eighty-five patients were randomly assigned. After 67 events, stratified analysis revealed that median progression-free survival was significantly shorter for apitolisib than for everolimus (3.7 v 6.1 months; hazard ratio, 2.12 [95% CI, 1.23 to 3.63; P < .01]); apitolisib was not favored in any stratification subgroup. Median overall survival was not significantly different but trended in favor of everolimus (16.5 v 22.8 months; hazard ratio, 1.77 [95% CI, 0.97 to 3.24; P = .06]). The objective response rate was 7.1% for apitolisib and 11.6% for everolimus. Patients administered apitolisib with a greater incidence of grade 3 to 4 adverse events were more likely to discontinue treatment (31% v 12% for everolimus). No drug-related deaths were observed. Apitolisib in comparison with everolimus was associated with substantially more high-grade hyperglycemia (40% v 9%) and rash (24% v 2%). Apitolisib pharmacokinetics suggested a relationship between exposure, and rash and hyperglycemia. Retrospective biomarker analyses revealed a relationship between VHL mutation status and outcome with everolimus but not with apitolisib. High hypoxia-inducible factor 1α protein expression was associated with better outcome in both arms. Conclusion This study demonstrated that dual PI3K/mTOR inhibition by apitolisib was less effective than was everolimus in mRCC, likely because full blockade of PI3K/mTOR signaling resulted in multiple on-target adverse events. VHL mutation and hypoxia-inducible factor 1α expression may be predictive of an mTOR inhibitor benefit, although prospective validation is required.

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