scholarly journals Changing Perspectives in Diabetic Macular Oedema – Recognising and Understanding Chronic Diabetic Macular Oedema

2014 ◽  
Vol 08 (02) ◽  
pp. 145
Author(s):  
Usha Chakravarthy ◽  
Albert Augustin ◽  
Yit Yang ◽  
Michael Diestelhorst ◽  
Pascale Massin ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Macular Oedema ◽  
Diabetic Macular Oedema ◽  
Clinical Trial Data ◽  
Fluocinolone Acetonide ◽  
Phase Iii ◽  
Real World Data ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase Iii Trials

The satellite symposium moderated by Usha Chakravarthy entitled ‘Changing Perspectives in Diabetic Macular Oedema: Recognising and Understanding Chronic Diabetic Macular Oedema’ was convened at the 2014 EURETINA Congress. The symposium discussed the multiple processes involved in chronic diabetic macular oedema (DMO) and the use of medications, in particular, corticosteroids in its management. As DMO progresses, inflammatory cytokines are up-regulated relative to vascular endothelial growth factor (VEGF) and these promote various pathways that ultimately result in retinal damage in chronic disease. It is important therefore that treatments for chronic DMO address this altered inflammatory cytokine profile to effectively manage the condition. ILUVIEN®, a 190 μg intravitreal implant in applicator (with a daily release rate of 0.2 μg/day fluocinolone acetonide [FAc] implant) is a second-line therapy indicated for the treatment of chronic DMO. This implant has been shown in phase III trials to lead to marked improvements in visual acuity and in retinal thickness in patients with chronic DMO that were insufficiently response to first-line therapy (i.e. laser). Clinical trial data strongly support the use of the FAc implant in chronic DMO and now ‘real world’ data from its use in regular clinical practice are becoming available and interim results complement those reported in a clinical trial setting.

Survival of Patients With Advanced Colorectal Cancer Improves With the Availability of Fluorouracil-Leucovorin, Irinotecan, and Oxaliplatin in the Course of Treatment

2004 ◽  
Vol 22 (7) ◽  
pp. 1209-1214 ◽  
Author(s):  
Axel Grothey ◽  
Daniel Sargent ◽  
Richard M. Goldberg ◽  
Hans-Joachim Schmoll
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Cytotoxic Agents ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase Iii Trials

Purpose Fluorouracil (FU)-leucovorin (LV), irinotecan, and oxaliplatin administered alone or in combination have proven effective in the treatment of advanced colorectal cancer (CRC). Combination protocols using FU-LV with either irinotecan or oxaliplatin are currently regarded as standard first-line therapies in this disease. However, the importance of the availability of all three active cytotoxic agents, FU-LV, irinotecan, and oxaliplatin, on overall survival (OS) has not yet been evaluated. Materials and Methods We analyzed data from seven recently published phase III trials in advanced CRC to correlate the percentage of patients receiving second-line therapy and the percentage of patients receiving all three agents with the reported median OS, using a weighted analysis. Results The reported median OS is significantly correlated with the percentage of patients who received all three drugs in the course of their disease (P = .0008) but not with the percentage of patients who received any second-line therapy (P = .19). In addition, the use of combination protocols as first-line therapy was associated with a significant improvement in median survival of 3.5 months (95% CI, 1.27 to 5.73 months; P = .0083). Conclusion Our results support the strategy of making these three active drugs available to all patients with advanced CRC who are candidates for such therapy to maximize OS. In addition, our findings suggest that, with the availability of effective salvage options, OS should no longer be regarded as the most appropriate end point by which to assess the efficacy of a palliative first-line treatment in CRC.

Comparison of the Efficacy and Toxicity of Fludarabine (F) in First Line Therapy of Younger Versus Elderly Patients (Pts) with Advanced Chronic Lymphocytic Leukemia (CLL): Results of a Meta-Analysis of Two Phase III Trials of the German CLL Study Group (GCLLSG).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 717-717 ◽  
Author(s):  
Barbara F. Eichhorst ◽  
Raymonde Busch ◽  
Clemens M. Wendtner ◽  
Michael Hallek ◽  
Keyword(s):  
Age Groups ◽  
The Elderly ◽  
Phase Iii ◽  
First Line ◽  
Two Phase ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase Iii Trials ◽  
Binet Stage ◽  
Grade 3

Abstract Introduction: F based regimen have become the standard treatment in CLL at least in younger pts. However, in elderly pts chlorambucil is still frequently used since it is easy to administer and has less side effects. Here we compare the efficacy and toxicity of F administered to younger pts and elderly pts treated between 1999 and 2004 within two phase III trials of GCLLSG. Patients: 362 pts (median age 59 [range 37–65] years) were randomized to F (n=182) or F plus cyclophosphamide (n=180) within the CLL4 trial. 191 elderly pts (median age 71 [range 65–79] years) were treated with F (92 pts) or chlorambucil (99 pts) within the CLL5 protocol. Inclusion criteria were identical in both trials except for age limits. All pts were previously untreated and in advanced stage Binet C or Binet B with symptoms which require therapy or Binet A with severe B-symptoms. In both studies the F regimen consisted of 30 mg/m2/day (d) IV for 5 consecutive days, every 28 d for up to 6 cycles. Anti-infective prophylaxis and growth factors were not given routinely in both trials. Results: Most of patients in both age groups were in Binet stage B (54% of the younger pts and 52% of the elderly), 35% in each age group were in Binet stage C, 11% and 13% respectively in Binet stage A. No significant difference in the main clinical features was observed except for a higher incidence of concomitant disease in the elderly (61% versus 36%, p=0.001). A mean number of 5.2 F courses was administered in the CLL4 trial and 4.9 courses in the CLL5 trial. The mean administered cumulative dose of F per pt was lower in the elderly pts (1076 mg vs. 1194 mg, p= 0.05). Overall response rates were similar in both arms, with 82.9% in the younger group and 85.7% in the elderly. The complete remission rate was 6.7% in the younger patients and 10.4% in the elderly (p= 0.3). After a follow up time of 24 months (mo) the progression-free survival (PFS) was significantly shorter in the elderly group with 18.7 mo compared to 19.8 mo in the younger group after 22 mo observation time (p=0.03). The overall survival (OS) was significantly impaired in elderly pts as well (29 mo versus median not reached, p<0.001). Progressive disease was the main cause of death in both age groups. In each group 3 treatment related deaths occurred due to infection or hemolysis. The incidence of side effects was similar in both age groups. Severe, CTC grade 3 and 4, myelosuppression occurred in 39% of the younger and 41% of the elderly pts. No difference in the rate of leukocytopenia, thrombocytopenia or anemia was oberved as well. The incidence rate and severity of infections was similar in both groups (24% vs. 32% all and 8.7% vs. 6.9% CTC grade 3 and 4). The incidence of second neoplasia was significantly higher in the elderly pts (2.2% vs. 12.2%, p=0.001). In comparison the prevalence rate of neoplasia in the U.S. population peaks at 11% in the age group of 70–79 (SEER cancer statistic review: 1972–2002). Conclusion: F is a well tolerated treatment regimen in first line therapy of elderly pts with CLL. Response rates were similar in both age groups. PFS and OS were significantly shorter in the elderly population. The incidence of second neoplasia was significantly higher in the elderly pts, but is only slightly increased in comparison to the normal population.

Irinotecan/5-FU/FA (I-FU) or 5-FU/FA (FU) first-line therapy in older and younger patients with metastatic colorectal cancer: Combined analysis of 2,691 patients in randomized controlled trials

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4071-4071 ◽  
Author(s):  
G. Folprecht ◽  
M. T. Seymour ◽  
L. Saltz ◽  
J. Y. Douillard ◽  
R. J. Stephens ◽  
...  
Keyword(s):  
Phase Iii ◽  
First Line ◽  
Younger Patients ◽  
Randomized Controlled ◽  
First Line Therapy ◽  
Line Therapy ◽  
Source Data ◽  
Phase Iii Trials ◽  
Receive Treatment ◽  
Ecog Ps

4071 Background: Irinotecan containing first line therapy has been shown to improve efficacy in first line therapy. Pooled analyses demonstrated that elderly patients benefit in a similar way as younger patients if 5-FU or 5-FU/oxaliplatin is administered as palliative or adjuvant treatment within clinical trials (Sargent, NEJM 2001, Folprecht, Ann Oncol 2004, Goldberg JCO 2006). Methods: We present an updated metaanalysis using source data of randomized trials (Saltz 2000, Douillard 2000, Köhne 2005 [EORTC 40986] and Seymour 2005 [FOCUS]) and compared the efficacy and toxicity in older (=70 years) and younger (<70 years) patients receiving first line 5- FU/FA with or without irinotecan. Randomized patients who did not receive treatment were excluded. Results: A total of 2,691 pts. was enrolled into the analysis ( table 1 ). There was no imbalance regarding risk factors (ECOG PS, WBC, No. of tumor sites, alkal. phosphatase, LDH) between elderly and younger patients. Older and younger patients had significantly improved response rates and PFS with I-FU compared to FU. Younger patients had significantly longer OS with I-FU, older patients a trend to longer OS with I-FU ( table 1 ). I- FU was associated with more grade >= 3 toxicity in the general population, but there were no significant differences regarding toxicity between older and younger patients ( table 1 ). Conclusion: Patients over 70 yrs who are selected for inclusion in phase III trials derive similar benefits from irinotecan-containing chemotherapy, and with similar risks of toxicity, compared with younger patients. [Table: see text] [Table: see text]

scholarly journals Ranibizumab in Diabetic Macular Oedema – A Benefit–risk Analysis of Ranibizumab 0.5 mg PRN Versus Laser Treatment

2017 ◽  
Vol 13 (02) ◽  
pp. 91 ◽  
Author(s):  
Focke Ziemssen ◽  
Alan Cruess ◽  
Cornelia Dunger-Baldauf ◽  
Philippe Margaron ◽  
Howard Snow ◽  
...  
Keyword(s):  
Macular Oedema ◽  
Risk Measures ◽  
Diabetic Macular Oedema ◽  
Risk Profile ◽  
Phase Iii ◽  
Action Team ◽  
Venous Thromboembolic Events ◽  
Venous Thromboembolic ◽  
Phase Iii Trials ◽  
One Year

Introduction: The structured Benefit–risk Action Team (BRAT) approach aims to assist healthcare decision makers in treatment assessments. We applied BRAT to compare the benefit–risk profile of ranibizumab 0.5 mg versus laser photocoagulation for the treatment of diabetic macular oedema (DMO). Methods: One-year data for the ranibizumab 0.5 mg pro re nata (PRN) and laser arms of the phase III trials RESPOND (NCT01135914; n=220), RESTORE (NCT00687804; n=345), and REVEAL (NCT00989989; n=396) were included in the analysis. The benefit measures included ≥10 letters gain/avoidance of loss in best-corrected visual acuity (BCVA), achieving central retinal thickness (CRT) <275 μm, and 25-item Visual Function Questionnaire (VFQ-25) outcomes. The risks measures included endophthalmitis, intraocular pressure increase, hypertension, proteinuria, arterial/venous thromboembolic events and deaths. Results: Ranibizumab treatment provided significant benefits compared with laser for ≥10 letter BCVA gain at month 12 (387/1,000 versus 152/1,000 patients), CRT <275 μm at 12 months (474/1,000 versus 348/1,000 patients), and improvement of ≥6.06 on the VFQ-25 near activities subscale (325/1,000 versus 245/1,000 patients). Results for the risk measures were similar for both treatments. Conclusions: Superior clinically relevant outcomes were observed with ranibizumab 0.5 mg PRN compared with laser without compromising on safety. This analysis further supports the positive benefit–risk profile of ranibizumab 0.5 mg PRN.

scholarly journals Retrospective Analysis of Treatment Patterns in Pseudophakic Diabetic Macular Oedema Eyes Treated with Anti-VEGF

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Di Zou ◽  
Imran Jawaid ◽  
Winfried M. Amoaku
Keyword(s):  
Macular Oedema ◽  
Functional Outcomes ◽  
Diabetic Macular Oedema ◽  
Prescribing Patterns ◽  
First Line ◽  
Real World Data ◽  
Treatment Delivery ◽  
First Line Therapy ◽  
Anti Vegf ◽  
Endothelial Growth Factor

Background/Objectives. Currently, in England, antivascular endothelial growth factor (anti-VEGF) is the first-line treatment for diabetic macular oedema (DMO) where central macular thickness (CMT) is ≥400 microns. In pseudophakic eyes with suboptimal response to first-line therapy, intravitreal corticosteroids may also be used. In practice, despite rigorous anti-VEGF therapy, suboptimal response occurs in nearly half of all eyes with DMO. The objective of this study was to investigate structural and functional outcomes and examine anti-VEGF treatment delivery in pseudophakic eyes receiving anti-VEGF injections for DMO. Methods. We performed a retrospective review of outcomes in 81 pseudophakic eyes with DMO that received at least 6 anti-VEGF injections. We reviewed baseline and posttreatment optical coherence tomography images, visual acuity, prescribing patterns, time taken to deliver anti-VEGF injections, and structural and functional outcomes. Results. It took an average of 913 ± 454.1 days to deliver a mean of 11.1 ± 4.7 anti-VEGF injections. Time from baseline to receiving the first 6 anti-VEGF injections was longer than 9 months in 74.7% (n = 59/79) of eyes. There was a mean gain of 1.6 letters (−0.03 logMAR) from baseline to the end point. After 5 anti-VEGF intravitreal injections, the mean CMT was 391.9 μm from 474.4 μm at baseline ( p < 0.0001 ). In 52 of 79 eyes (65.8%), more than one type of anti-VEGF agent was used. Conclusions. The anti-VEGF treatment used to treat these eyes with DMO was suboptimal, a finding consistent with recently published “real-world” data. There was a strong tendency for patients to be switched within the class to a second anti-VEGF agent.

Management of Diabetic Macular Oedema – Challenges and Solutions Along the Patient Journey

2013 ◽  
Vol 07 (02) ◽  
pp. 115
Author(s):  
Albert J Augustin ◽  
Sue Lightman ◽  
Anat Loewenstein ◽  
José Cunha-Vaz
Keyword(s):  
Macular Oedema ◽  
Diabetic Macular Oedema ◽  
Clinical Trial Data ◽  
Fluocinolone Acetonide ◽  
Patient Journey ◽  
Anti Vegf ◽  
Long Duration ◽  
Intravitreal Implant ◽  
Disease Stages ◽  
Endothelial Growth Factor

A symposium hosted by the European Society of Ophthalmology discussed challenges in the management of diabetic macular oedema (DMO). Clinical evidence suggests that the longer the duration of DMO, the worse the response to anti-vascular endothelial growth factor (anti-VEGF) agents and better the response to corticosteroids. This is explained by the fact that inflammation is involved in the perpetuation of retinal changes in diabetes. At early disease stages, VEGF is primarily responsible for retinal changes; however, chronic microglia activation resulting from retinal damage leads to cytokine production by retinal cells and subsequent inflammatory cascades. Steroids are most effective at this stage. Clinical trial data have demonstrated the efficacy of the Iluvien® fluocinolone acetonide (FA) intravitreal implant, which retains its efficacy in disease of long duration. However, it is important to remember two things: that diabetes is a multifactorial disease with potential complications and to monitor for safety effects. In terms of the latter, anti-VEGF agents are associated with potential systemic effects, whereas steroids raise intraocular pressure and are associated with increased incidence of cataract.

Prescribing preferences (PPrefs) of U.S.-based medical oncologists (MOs) for choice of therapy after failure of first-line FOLFOX plus bevacizumab (FFB) in patients with metastatic colorectal cancer (MCC).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 533-533
Author(s):  
Johanna C. Bendell ◽  
Susan L. Britton ◽  
Maria Lankford ◽  
Arden Buettner ◽  
Mark R. Green ◽  
...  
Keyword(s):  
Lung Metastases ◽  
Real Life ◽  
Phase Iii ◽  
Audience Response ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Best Response ◽  
Phase Iii Trials

533 Background: Phase III trials have tested biologic (bio) agents (bevacizumab [bev], anti-EGFR antibodies, ziv aflibercept [ziv]) plus chemotherapy (CT) vs. CT alone after failure of first-line therapy in patients given CT + bev first line. Several have shown improvements in progression-free and overall survival (OS) with the CT + bio approach, but it is not clear how these therapies are being used in the “real life” setting. Methods: Since 3/2013 PPrefs for this setting among 276 MOs were studied using a validated, proprietary, live, case-based market research tool. A core scenario and variations based on KRAS status and first-line therapy outcome were tested (S1, S2, S3, S4). PPref data acquired using blinded audience response technology. All sources of research support were blinded. Core scenario: 49 yr old female with cecal mass, liver/lung metastases, confirmed wt KRAS for S1-3, given FFB first line. S1: FFB x 16 wks → excellent PR → 5FU bev X 16 wks → progressive disease [PD]; S2: FFB x 16 wks → excellent PR → bev alone x 16 wks → PD; S3: FFB → stable disease [SD] x 5 months as best response [BR] → PD; 4) Here changed to mutKRAS; FFB x 8 wks → PD as BR. Results: Findings shown below (Table). Conclusions: In scenarios with wt KRAS, first-line response to FFB, a majority plan bev again second line. If BR to FFB is SD in WT KRAS, anti-EGFR antibody-based therapy is used more often. In S 1-3, ziv is the PPref of 7 - 14% of MOs studied. With mutKRAS and PD as BR to FFB, use of an antiangiogenic + second-line CT is preferred by > 80%, nearly equally split between bev and ziv. Recent phase III trial data showing OS benefits are reflected in current MOs first failure PPrefs. [Table: see text]

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