Front-Line FLAG-IDA and Nove-HiDAC Chemotherapy Improves Overall Survival (OS) and Complete Remission Rates (CR) for Patients with Secondary or Therapy-Related AML Compared to 3&7

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4893-4893
Author(s):  
Sita D. Bhella ◽  
Eshetu G Atenafu ◽  
Andre C Schuh ◽  
Mark D. Minden ◽  
Aaron D. Schimmer ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Complete Remission ◽  
Invasive Aspergillosis ◽  
Myeloproliferative Neoplasm ◽  
Rank Test ◽  
P Value ◽  
Front Line ◽  
First Line ◽  
Poor Risk

Abstract Background: Therapy for patients (pts) with high risk AML remains unsatisfactory. Retrospective studies have demonstrated activity of fludarabine, cytarabine, GCSF and idarubicin (FLAG-IDA) and of mitoxantrone, etoposide and cytarabine (NOVE-HiDAC) as salvage therapy in pts with relapsed or refractory AML. A recent randomized trial indicated high complete remission (CR) rates with improved relapsed-free survival when FLAG-IDA is administered as frontline induction therapy (Burnett et al. J Clin Oncol 2013). Since 01/2011, we have used FLAG-IDA as a first line therapeutic option in pts with high risk AML (poor risk cytogenetics, antecedent myeloproliferative neoplasm or myelodysplastic syndrome, and/or therapy-related AML) in an attempt to improve CR rates and permit more patients with AML to advance to allogeneic hematopoietic cell transplantation (alloHCT). Prior to 2011, either 3&7 or NOVE-HiDAC was used as first line therapy in patients with AML. Methods: We conducted a retrospective review of consecutive patients with high risk AML treated with front-line (a) FLAG-IDA between 01/2011 to 03/2015, (b) NOVE-HiDAC from 01/2006 to 12/2014, or (c) 3&7 from January 01/2011 to 12/2014 at the Princess Margaret Cancer Centre, to determine the CR rates and overall survival (OS) associated with the different regimens. Results: Patients characteristics are in Table 1. Fifty-two, 32, and 30 pts received FLAG-IDA, NOVE-HiDAC or 3&7 as first induction, respectively. Patients receiving FLAG-IDA had more high-risk features (i.e. complex cytogenetics, more azacytidine failures) compared to those receiving 3&7. Overall CR rate (i.e. CR + [CRi] + [CRp]) with FLAG-IDA, NOVE-HiDAC, and 3&7 respectively was 86% (n=42/49), 84% (n=21/25) and 50% (n=13/26), respectively. Median CR duration, censored at time of transplant, for pts receiving FLAG-IDA, NOVE-HiDAC and 3&7 was 3 mos (0.5-15), 3.5 mos (1-9) and 5.5 mos (0.5-42), respectively. OS at 1 year with FLAG-IDA, NOVE-HiDAC and 3&7 was 61% (95% CI, 41% -75%), 55% (95% CI, 34%-72%) and 21.6% (95% CI, 7.4%-40.7%), respectively (log-rank test p-value=0.0076). On subgroup analysis, there was no statistical difference in OS for pts ≥70 years. Of those with a donor identified, 35% (n=13/37), 73% (n=11/15) and 29% (n=5/17) of pts who were treated with FLAG-IDA, NOVE-HiDAC and 3&7 underwent an alloSCT, respectively. Pts with sAML may have had a higher transplant rate due to donor searches initiated earlier. Probable and possible invasive aspergillosis infections in pts receiving FLAG-IDA, NOVE-HiDAC and 3&7 were 50%, 34% and 33% respectively. Institution of earlier bronchoscopies led to increased fungal detection in the FLAG-IDA group. Median length of stay and ICU transfers were similar between groups. Induction deaths were secondary to sepsis, respiratory failure, invasive aspergillosis, and hemorrhage; these were similar across groups. Two pts receiving NOVE-HiDAC, with prior MPN, died of progressive splenomegaly and liver failure. Conclusions: Toxicities associated with frontline FLAG-IDA and NOVE-HIDAC induction are acceptable. FLAG-IDA and NOVE-HiDAC induction can result in durable CR, permitting patients with high risk AML to proceed to alloSCT and providing more favourable survival rates than frontline 3&7. Randomized studies are needed to confirm these findings for pts with poor-risk sAML and tAML. Table 1. Patient Characteristics FLAG-IDA(2013-2015) NOVE-HiDAC(2006-2014) 3&7(2011-2014) N=52 N=32 N=30 Median Age,y (range) Age <70 Age ≥ 70 Sex (M:F) 59.5 (21-76) 47 (90%) 5 (10%) 25:27 54.5 (24-74) 31 (97%) 1 (3%) 18:14 61.5 (20-78) 21 (70%) 9 (30%) 23:7 Cytogenetics by MRC Classification Good Intermediate Poor Not available 0 (0%) 25 (48%) 23 (44%) 4 (8%) 0 (0%) 18 (56%) 9 (28%) 5 (16%) 0 (0%) 20 (67%) 6 (20%) 4 (13%) Molecular (Pts ≤70 y with normal karyotype) FLT3-NPM1+ FLT3+ NPM1+ FLT3+ NPM1- FLT3-NPM1- 1/11 (9%) 5/11 (45%) 2/11 (18%) 3/11 (27%) 0/7 (0%) 2/7 (29%) 1/7 (14%) 4/7 (57%) 0/7 (0%) 1/7 (14%) 0/7 (0%) 6/7 (86%) WBC (x 109/L) (range) 5.15 (0.6 -239) 13 (1.3-182.4) 3.2 (0.7-164) sAML IBMFS MPN MDS Prior AZA 27 (52%) 0/27 (0%) 10/27 (37%) 17/27 (63%) 9/17 (53%) 29 (91%) 1/29 (4%) 15/29 (51%) 13/29 (45%) 2/13 (15%) 20 (67%) 2/20 (10%) 0/20 (0%) 18/20 (90%) 5/18 (28%) Therapy-Related (%) 14 (27%) 6 (19%) 15 (50%) De Novo AML with Complex Cytogenetics FLT3+ Other (ie MLL) 15 (29%) 7/15 (47%) 5/15 (33%) 3/15 (20%) 0 (0%) 0 (0%) Donor Identified (%) 37(71%) 16(50%) 17(57%) Disclosures Gupta: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Research Funding.

Further Evidence to Not Delay Transplant for Continued ARA-C Consolidation in Patients with Intermediate or High Risk AML

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5544-5544
Author(s):  
James K. Feisal ◽  
Nicholas B. Pleat ◽  
Michael Machiorlatti ◽  
Summer Frank ◽  
Sara Vesley ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Complete Remission ◽  
Blood Cells ◽  
P Value ◽  
Myeloablative Conditioning ◽  
Risk Status ◽  
Post Transplant ◽  
Preparative Regimen ◽  
Reduced Intensity

Abstract Background: Allogeneic stem cell transplant (alloSCT) is indicated for patients with acute myeloid leukemia (AML) with high-risk disease on presentation or in relapsed or refractory cases. Durable elimination of leukemic burden after achieving a complete remission (CR) is thought to be an important prerequisite for successful transplant. Typically, this is achieved with consolidation treatments with cytarabine (ARA-C) in repeated cycles in non-refractory cases. Previous reports have suggested there is no apparent advantage for post-remission consolidation chemotherapy before reduced intensity transplant, provided a donor is readily available. Aim: To study the impact of the total cumulative dose of ARA-C in the pre-transplant setting before alloSCT either with reduced-intensity conditioning (RIC) or full myeloablative conditioning (MAC). Methods: We conducted a retrospective chart review at the University of Oklahoma and affiliated hospitals in patients with AML in complete remission from October 2006 to December 2014. Appropriate IRB approval was obtained in accordance with Helsinki declaration. Simple descriptive statistics were created for all covariates [mean, SD for continuous covariates and n (%) for categorical variables]. A Cox proportional hazards model was used to assess the association of each covariate with overall survival. Results: Sixty five patients were identified through our local leukemia registry with a mean age of 43, 57 (87.7%) were white, and 42 (64.6%) were male. Based on cytogenetics and molecular markers, 36 patients (55.3%) were intermediate risk and 20 patients (30.7%) were unfavorable risk status. For transplant preparative regimen, MAC was utilized in 50 cases (76.9%) and RIC was utilized in the other 15 (23.0%). Bone marrow stem cells were used in 28 cases (43.0%), peripheral blood cells were used in 26 cases (40.0%), and cord blood cells were used in the remaining 11 cases (16.9%). The mean dose of ARA-C given in consolidation was 43 g/m2 with standard deviation 31.5 g/m2. After adjusting for age and risk status, ARA-C consolidation was not associated with increased overall survival (OS) in the patients (p-value = 0.1776). When only considering those patients with myeloablative conditioning, ARA-C consolidation was still not associated with increased OS (p-value = 0.7533). Conclusions: Prior published data indicates that further ARA-C therapy given during consolidation does not correlate with improved outcomes post-transplant in patients with AML who received a reduced intensity preparative regimen. However, we attempted to expand this data to include patients who received a full myeloablative preparative regimen. Our experience using our single institution retrospective data suggests further ARA-C therapy given in consolidation does not benefit patients who underwent either RIC or MAC in terms of post-transplant survival. This provides further evidence that there should be no delay in moving patients to transplant, provided a suitable donor is available. Disclosures No relevant conflicts of interest to declare.

scholarly journals Improved Survival of Patients with Myelofibrosis in the Last Decade

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 50-51
Author(s):  
Lucia Masarova ◽  
Prithviraj Bose ◽  
Naveen Pemmaraju ◽  
Lingsha Zhou ◽  
Sherry A. Pierce ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Research Funding ◽  
Myeloproliferative Neoplasm ◽  
Categorical Variables ◽  
Rank Test ◽  
Fisher Exact Test ◽  
Grant Support ◽  
Before And After

Introduction: The myeloproliferative neoplasm myelofibrosis (MF) is associated with reduced overall survival (OS) compared to the general population. In 2011, the JAK1/2 inhibitor ruxolitinib, was approved in the USA for the treatment of intermediate and high-risk MF. Long-term follow-up of patients in pivotal phase 3 studies showed survival benefit of ruxolitinib therapy. Objective: We sought to evaluate the outcome of patients with MF diagnosed before and after the year of 2010 to assess whether OS changed in the past decade in the era of ruxolitinib. Methods: We retrospectively reviewed the charts of 1346 patients with MF who presented to our institution in the last 25 years and compared clinical parameters and outcomes between those presented before and after the year of 2010 (before / after y. 2010). Newly diagnosed MF patients and patients within 12 months from diagnosis who were previously only treated with supportive therapy (danazol, growth-factors, steroids) were included. Cytogenetics (≥10 metaphases) was classified according to Gangat, JCO, 2011. Molecular analysis (≥ 28 genes) was performed only after y. 2010 by using next generation sequencing platform. Fisher exact test and χ2 were used for analysis of categorical variables. Overall survival (OS) was estimated using the Kaplan-Meier method and comparison was done by the log-rank test. Results: Among the 1346 patients, 806 (60%) patients were seen after y. 2010. Median age of all patients was 65 years (range, 20-94), 62% were males. Patient characteristics with comparison between groups are shown in Table 1. Patients after y. 2010 were older, with lower WBC and lower lactate dehydrogenase, but had more symptoms. The distribution of IPSS scores between groups were comparable at around 10% for low, 36% for intermediate-1, 20-25% for intermediate-2 and ~30% for high risk. Eighty-five and 80% of patients before and after y. 2010, respectively, received therapy for MF at our institution. Overall, 78 patients (37 after y. 2010) underwent stem cell transplantation. Among treated patients at our institution, 25% (n 117) and 37% (n 241) before and after y. 2010 received ruxolitinib during their follow-up. Ruxolitinib therapy was initiated with a median time of 2 months (range, 0.2-156) from presentation to our institution, longer in those before y. 2010 (11 vs 1 months in patients after y. 2010, respectively, p = 0.001) After a median follow-up of 30.4 months (range, 0.9-266); 659 (49%) of patients died. More deaths were noticed in those before y. 2010 (74% vs 32 %, respectively, p &lt; 0.001); but these patients had also longer follow-up (37.5 months vs 25 months, p &lt; 0.001). Eighty-five patients (10%) developed acute leukemia: 2 cases per 100 person-years per observation for both groups. Patients after y. 2010 had superior OS to those before y. 2010 with HR 0.7 (95% CI: 0.59-0.82), p &lt; 0.001, Figure 1. Superior OS was observed in all patients after y. 2010 (vs before y. 2010) when stratified by IPSS score (higher equals for combination of int -2 and high, Figure 2), or age (cutoff of 65 years, Figure 3). Patients exposed to ruxolitinib had superior OS regardless of being diagnosed before or after y. 2010, with respective medians of 98 (95% CI: 78-118) and 91 (95% CI: 73-109) months (details to be presented at the conference). Conclusion: Our results demonstrate that survival of patients with MF has improved in the last decade. Survival has improved in younger and older patients as well as in those with more advanced disease (per IPSS risks). Many factors may have contributed to the observed improvement in outcome of MF patients, including new therapies, e.g. ruxolitinib, as well as improved supportive management and disease awareness. Disclosures Bose: Blueprint Medicines Corporation: Honoraria, Research Funding; Astellas Pharmaceuticals: Research Funding; Kartos Therapeutics: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding; Incyte Corporation: Consultancy, Honoraria, Research Funding, Speakers Bureau; NS Pharma: Research Funding; Constellation Pharmaceuticals: Research Funding; Pfizer, Inc.: Research Funding; CTI BioPharma: Honoraria, Research Funding; Promedior, Inc.: Research Funding. Pemmaraju:Daiichi Sankyo: Research Funding; DAVA Oncology: Honoraria; Blueprint Medicines: Honoraria; Roche Diagnostics: Honoraria; AbbVie: Honoraria, Research Funding; Celgene: Honoraria; Incyte Corporation: Honoraria; MustangBio: Honoraria; Plexxikon: Research Funding; Samus Therapeutics: Research Funding; SagerStrong Foundation: Other: Grant Support; Novartis: Honoraria, Research Funding; Pacylex Pharmaceuticals: Consultancy; Affymetrix: Other: Grant Support, Research Funding; LFB Biotechnologies: Honoraria; Stemline Therapeutics: Honoraria, Research Funding; Cellectis: Research Funding. Kantarjian:Novartis: Research Funding; Ariad: Research Funding; Jazz Pharma: Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Cyclacel: Research Funding; Pfizer: Honoraria, Research Funding; Daiichi-Sankyo: Research Funding; Amgen: Honoraria, Research Funding; Immunogen: Research Funding; Astex: Research Funding; Takeda: Honoraria; Agios: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; BMS: Research Funding. Verstovsek:CTI Biopharma Corp: Research Funding; Protagonist Therapeutics: Research Funding; PharmaEssentia: Research Funding; ItalPharma: Research Funding; Gilead: Research Funding; Promedior: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Consultancy, Research Funding; Incyte Corporation: Consultancy, Research Funding; Roche: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Research Funding; Blueprint Medicines Corp: Research Funding; Genentech: Research Funding; AstraZeneca: Research Funding.

scholarly journals POS0619 MODELLING OF DISEASE ACTIVITY IN PATIENTS WITH INFLAMMATORY ARTHROPATHIES TREATED WITH ETANERCEPT ORIGINATOR OR BIOSIMILAR AS FIRST-LINE BIOLOGIC IN AN AUSTRALIAN REAL-WORLD DATASET

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 547.1-547
Author(s):  
C. Deakin ◽  
G. Littlejohn ◽  
H. Griffiths ◽  
T. Smith ◽  
C. Osullivan ◽  
...  
Keyword(s):  
Disease Activity ◽  
Clinical Data ◽  
Real World ◽  
Rank Test ◽  
P Value ◽  
Continuous Variables ◽  
Linear Quadratic ◽  
First Line ◽  
Modest Improvement ◽  
Over Time

Background:The availability of biosimilars as non-proprietary versions of established biologic disease-modifying anti-rheumatic drugs (bDMARDs) is enabling greater access for patients with rheumatic diseases to effective medications at a lower cost. Since April 2017 both the originator and a biosimilar for etanercept (trade names Enbrel and Brenzys, respectively) have been available for use in Australia.Objectives:[1]To model effectiveness of etanercept originator or biosimilar in reducing Disease Activity Score 28-joint count C reactive protein (DAS28CRP) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS) treated with either drug as first-line bDMARD[2]To describe persistence on etanercept originator or biosimilar as first-line bDMARD in patients with RA, PsA or ASMethods:Clinical data were obtained from the Optimising Patient outcomes in Australian rheumatoLogy (OPAL) dataset, derived from electronic medical records. Eligible patients with RA, PsA or AS who initiated etanercept originator (n=856) or biosimilar (n=477) as first-line bDMARD between 1 April 2017 and 31 December 2020 were identified. Propensity score matching was performed to select patients on originator (n=230) or biosimilar (n=136) with similar characteristics in terms of diagnosis, disease duration, joint count, age, sex and concomitant medications. Data on clinical outcomes were recorded at 3 months after baseline, and then at 6-monthly intervals. Outcomes data that were missing at a recorded visit were imputed.Effectiveness of the originator, relative to the biosimilar, for reducing DAS28CRP over time was modelled in the matched population using linear mixed models with both random intercepts and slopes to allow for individual heterogeneity, and weighting of individuals by inverse probability of treatment weights to ensure comparability between treatment groups. Time was modelled as a combination of linear, quadratic and cubic continuous variables.Persistence on the originator or biosimilar was analysed using survival analysis (log-rank test).Results:Reduction in DAS28CRP was associated with both time and etanercept originator treatment (Table 1). The conditional R-squared for the model was 0.31. The average predicted DAS28CRP at baseline, 3 months, 6 months, 9 months and 12 months were 4.0 and 4.4, 3.1 and 3.4, 2.6 and 2.8, 2.3 and 2.6, and 2.2 and 2.4 for the originator and biosimilar, respectively, indicating a clinically meaningful effect of time for patients on either drug and an additional modest improvement for patients on the originator.Median time to 50% of patients stopping treatment was 25.5 months for the originator and 24.1 months for the biosimilar (p=0.53). An adverse event was the reason for discontinuing treatment in 33 patients (14.5%) on the originator and 18 patients (12.9%) on the biosimilar.Conclusion:Analysis using a large national real-world dataset showed treatment with either the etanercept originator or the biosimilar was associated with a reduction in DAS28CRP over time, with the originator being associated with a further modest reduction in DAS28CRP that was not clinically significant. Persistence on treatment was not different between the two drugs.Table 1.Respondent characteristics.Fixed EffectEstimate95% Confidence Intervalp-valueTime (linear)0.900.89, 0.911.5e-63Time (quadratic)1.011.00, 1.011.3e-33Time (cubic)1.001.00, 1.007.1e-23Originator0.910.86, 0.960.0013Acknowledgements:The authors acknowledge the members of OPAL Rheumatology Ltd and their patients for providing clinical data for this study, and Software4Specialists Pty Ltd for providing the Audit4 platform.Supported in part by a research grant from Investigator-Initiated Studies Program of Merck & Co Inc, Kenilworth, NJ, USA. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck & Co Inc, Kenilworth, NJ, USA.Disclosure of Interests:Claire Deakin: None declared, Geoff Littlejohn Consultant of: Over the last 5 years Geoffrey Littlejohn has received educational grants and consulting fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Gilead, Novartis, Pfizer, Janssen, Sandoz, Sanofi and Seqirus., Hedley Griffiths Consultant of: AbbVie, Gilead, Novartis and Lilly., Tegan Smith: None declared, Catherine OSullivan: None declared, Paul Bird Speakers bureau: Eli Lilly, abbvie, pfizer, BMS, UCB, Gilead, Novartis

scholarly journals IL15RA and SMAD3 Genetic Variants Predict Overall Survival in Metastatic Colorectal Cancer Patients Treated with FOLFIRI Therapy: A New Paradigm

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1705
Author(s):  
Elena De Mattia ◽  
Jerry Polesel ◽  
Rossana Roncato ◽  
Adrien Labriet ◽  
Alessia Bignucolo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Prognostic Score ◽  
Chemotherapeutic Agents ◽  
Rank Test ◽  
P Value ◽  
Genetic Determinants ◽  
New Paradigm

A new paradigm in cancer chemotherapy derives from the interaction between chemotherapeutics, including irinotecan and 5-fluorouracil (5-FU), and the immune system. The patient’s immune response can modulate chemotherapy effectiveness, and, on the other hand, chemotherapeutic agents can foster tumor cell immunogenicity. On these grounds, the analysis of the cancer patients’ immunogenetic characteristics and their effect on survival after chemotherapy represent a new frontier. This study aims to identify genetic determinants in the immuno-related pathways predictive of overall survival (OS) after FOLFIRI (irinotecan, 5-FU, leucovorin) therapy. Two independent cohorts comprising a total of 335 patients with metastatic colorectal cancer (mCRC) homogeneously treated with first-line FOLFIRI were included in the study. The prognostic effect of 192 tagging genetic polymorphisms in 34 immune-related genes was evaluated using the bead array technology. The IL15RA rs7910212-C allele was associated with worse OS in both discovery (HR: 1.57, p = 0.0327, Bootstrap p-value = 0.0280) and replication (HR:1.71, p = 0.0411) cohorts. Conversely, SMAD3 rs7179840-C allele was associated with better OS in both discovery (HR:0.65, p = 0.0202, Bootstrap p-value = 0.0203) and replication (HR:0.61, p = 0.0216) cohorts. A genetic prognostic score was generated integrating IL15RA-rs7910212 and SMAD3-rs7179840 markers with inflammation-related prognostic polymorphisms we previously identified in the same study population (i.e., PXR [NR1I2]-rs1054190, VDR-rs7299460). The calculated genetic score successfully discriminated patients with different survival probabilities (p < 0.0001 log-rank test). These findings provide new insight on the prognostic value of genetic determinants, such as IL15RA and SMAD3 markers, and could offer a new decision tool to improve the clinical management of patients with mCRC receiving FOLFIRI.

Efficacy and prognostic significance of triflurodine/tipiracil beyond oxaliplatin and irinotecan based chemotherapy in patients with refractory metastatic colorectal cancer: An observational multicenter study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15586-e15586
Author(s):  
Mohamed Alghamdi ◽  
Shouki Bazarbashi ◽  
Elsamany Shereef ◽  
Mervat Mahrous ◽  
Omar Al shaer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Saudi Arabia ◽  
Neutrophil Count ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
P Value ◽  
Second Line ◽  
First Line ◽  
Free Survival

e15586 Background: In Saudi Arabia, the incidence of colorectal cancer has been increased over the past few years. The optimal treatment beyond the second line is not fully understood. To the best of our knowledge, the efficacy and disease outcomes of triflurodine/tipiracil in Saudi patients with refractory metastatic colorectal cancer(mCRC) has not been studied yet. Our study is a real-life practice evaluation of the efficacy of triflurodine/tipiracil in patients with refractory mCRC. Moreover, the prognosis and the prognostic significance of the different clinical variables have been analyzed. Methods: A retrospective, multi-centers ( 5 centers representative of Saudi Arabia )observational study in patients with mCRC who have received triflurodine/tipiracil beyond oxaliplatin & Irinotecan-based chemotherapy between December 2018-December 2020.We aimed to assess the response to triflurodine/tipiracil, to evaluate the progression-free survival (PFS ), the overall survival (OS), and the associated factors of prognostic significance. Results:The data of 100 patients with refractory mCRC who has received triflurodine/tipiracil have been analyzed. The mean age was 55.2 +11.8 years. Forty-two patients were (42%) females and 58 (58%) were male patients. Sigmoid was the most common primary site of cancer in 35 (35%) patients, followed by rectum 29 (29%). Peritoneal metastasis was present in 17 (23.3%) patients ,liver in 51(56.6%) and lung in 39 (50.7%). Metastatic sites were ≥ 2 in 45 (45%) patients. Metastatic lesions were ≥ 5 in 65 (65%) patients. Xelox chemotherapy regimen was the most commonly used first-line chemotherapy which represents 43%, while Folfiri or Xeliri combination was the most used second line in 57 (60%). For the third line, Folfox or Xelox was used in 81 (83.5%) patients. The fourth line was given to 49 (67.1%). For first-line biological agents, Cetuximab was used most frequently 31 (46.3%).Evaluation of the response to treatment with triflurodine/tipiracil revealed one patient (1%) with a complete response,3 patients (3%) with partial response, 28 (28%) patients with stable disease, and 66 (66%) showed progressive disease. The estimated median progression-free survival was 5 months ( 3.839 - 6.161) and the median overall survival was 12 months (9.732-14.268). The log-rank analysis showed that the baseline neutrophils ≤ 75 % ( P-value= 0.0092) and low hemoglobin level (P-value= 0.0245) were strongly associated with a higher survival. By multivariate Cox regression analysis, the neutrophil count ≤ 75 % was the only independent predictor for survival. Conclusions: Trifluridine/tipiracil is effective in patients with refractory mCRC. The low neutrophil count might predict a better overall survival.

Treatment of Pulmonary Metastases in Children With Stage IV Nephroblastoma With Risk-Based Use of Pulmonary Radiotherapy

2012 ◽  
Vol 30 (28) ◽  
pp. 3533-3539 ◽  
Author(s):  
Arnauld Verschuur ◽  
Harm Van Tinteren ◽  
Norbert Graf ◽  
Christophe Bergeron ◽  
Bengt Sandstedt ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
High Risk ◽  
Pulmonary Metastases ◽  
Stage Iv ◽  
Line Treatment ◽  
Event Free Survival ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

Purpose The purpose of this study was to determine the outcome of children with nephroblastoma and pulmonary metastases (PM) treated according to International Society of Pediatric Oncology (SIOP) 93-01 recommendations using pulmonary radiotherapy (RT) in selected patients. Patients and Methods Patients (6 months to 18 years) were treated with preoperative chemotherapy consisting of 6 weeks of vincristine, dactinomycin, and epirubicin or doxorubicin. If pulmonary complete remission (CR) was not obtained, metastasectomy was considered. Patients in CR received three-drug postoperative chemotherapy, whereas patients not in CR were switched to a high-risk (HR) regimen with an assessment at week 11. If CR was not obtained, pulmonary RT was mandatory. Results Two hundred thirty-four of 1,770 patients had PM. Patients with PM were older (P < .001) and had larger tumor volumes compared with nonmetastatic patients (P < .001). Eighty-four percent of patients were in CR postoperatively, with 17% requiring metastasectomy. Thirty-five patients (16%) had multiple inoperable PM and required the HR protocol. Only 14% of patients received pulmonary RT during first-line treatment. For patients with PM, 5-year event-free survival rate was 73% (95% CI, 68% to 79%), and 5-year overall survival (OS) rate was 82% (95% CI, 77% to 88%). Five-year OS was similar for patients with local stage I and II disease (92% and 90%, respectively) but lower for patients with local stage III disease (68%; P < .001). Patients in CR after chemotherapy only and patients in CR after chemotherapy and metastasectomy had a better outcome than patients with multiple unresectable PM (5-year OS, 88%, 92%, and 48%, respectively; P < .001). Conclusion Following the SIOP protocol, pulmonary RT can be omitted for a majority of patients with PM and results in a relatively good outcome.

scholarly journals The first-line therapy of aggressive non-Hodgkin’s lymphomas in russian clinical practice: data from the EQUILIBRIUM study

2020 ◽  
Vol 15 (2) ◽  
pp. 10-18
Author(s):  
L. G. Babicheva ◽  
I. V. Poddubnaya
Keyword(s):  
Overall Survival ◽  
Clinical Practice ◽  
Complete Remission ◽  
B Cell ◽  
Long Term Results ◽  
First Line ◽  
Therapy Efficacy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Hodgkin's Lymphomas

The objective: evaluation of effectiveness of the first-line therapy with rituximab of B-cell lymphoproliferative diseases in Russian clinical practice in the period from 2014 to 2017.Materials and methods. The EQUILIBRIUM post-registration multicenter study included 1000 patients aged 21 to 91 years old with a verified diagnosis of B-cell non-Hodgkin’s lymphoma, or chronic lymphocytic leukemia, who received at least 4 cycles of rituximab-containing therapy with Acellbia®. The group of aggressive non-Hodgkin’s lymphomas (aNHL), which is the subject of this article, included 295 patients with a median age of 55.9 years: diffuse B-large cell lymphoma – 87 %, primary mediastinal lymphoma – 11 %, Burkitt’s lymphoma – 1 %. Group characterized by the presence of aggressive clinical signs reflecting the poor prognosis: in the majority of patients, generalized stages were diagnosed (61 %), in half of the cases (50.2 %), extranodal localization of tumor foci was detected (in 32.4 % of patients there were 2 or more). The overwhelming majority of patients (84.5 %) received adequate treatment complying with national and international recommendations (R-CHOP, R-CHOEP and R-EPOCH, high-intensity NHL-BFM-R, R-HyperCVAD and R-MACOP-B regimes). The use of R-CVP, FCR, RB, Chl-R, R-monotherapy treatment programs (which received 15.5 % of patients) was considered inadequate for this category of patients.Results. According to the results of the final assessment, high therapy efficacy was established: the overall response exceeded 90 %, complete remission was achieved in most patients with aNHL (68.5 %), partial remission – in every 5th patient (21.8 %). With a median follow-up of 15 months, 16 (5.42 %) deaths and 34 (11.53 %) events were registered. Median of event-free survival and overall survival have not been achieved. Statistically significant differences depending on first-line therapy efficacy were found in overall survival (p = 0.00000) and eventfree survival (p = 0.00000), once again confirming that the main goal of aNHL treatment is to achieve complete remission.Conclusion. Available and compliant with national clinical guidelines treatment of aNHL patients with Russian bioanalogue of anti-CD20 monoclonal antibodies (Acellbia®) demonstrates high immediate efficacy and acceptable long-term results, comparable to a retrospective analysis of previous clinical studies of the original drug rituximab.

scholarly journals Paclitaxel, Ifosfamide, and Cisplatin Efficacy for First-Line Treatment of Patients With Intermediate- or Poor-Risk Germ Cell Tumors

2016 ◽  
Vol 34 (21) ◽  
pp. 2478-2483 ◽  
Author(s):  
Darren R. Feldman ◽  
James Hu ◽  
Tanya B. Dorff ◽  
Kristina Lim ◽  
Sujata Patil ◽  
...  
Keyword(s):  
Overall Survival ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
Collaborative Group ◽  
Intermediate Risk ◽  
First Line ◽  
Free Survival ◽  
Poor Risk ◽  
End Point

Purpose Paclitaxel, ifosfamide, and cisplatin (TIP) achieved complete responses (CRs) in two thirds of patients with advanced germ cell tumors (GCTs) who relapsed after first-line chemotherapy with cisplatin and etoposide with or without bleomycin. We tested the efficacy of first-line TIP in patients with intermediate- or poor-risk disease. Patients and Methods In this prospective, multicenter, single-arm phase II trial, previously untreated patients with International Germ Cell Cancer Collaborative Group poor-risk or modified intermediate-risk GCTs received four cycles of TIP (paclitaxel 240 mg/m2 over 2 days, ifosfamide 6 g/m2 over 5 days with mesna support, and cisplatin 100 mg/m2 over 5 days) once every 3 weeks with granulocyte colony-stimulating factor support. The primary end point was the CR rate. Results Of the first 41 evaluable patients, 28 (68%) achieved a CR, meeting the primary efficacy end point. After additional accrual on an extension phase, total enrollment was 60 patients, including 40 (67%) with poor risk and 20 (33%) with intermediate risk. Thirty-eight (68%) of 56 evaluable patients achieved a CR and seven (13%) achieved partial responses with negative markers (PR-negative) for a favorable response rate of 80%. Five of seven achieving PR-negative status had seminoma and therefore did not undergo postchemotherapy resection of residual masses. Estimated 3-year progression-free survival and overall survival rates were 72% (poor risk, 63%; intermediate risk, 90%) and 91% (poor risk, 87%; intermediate risk, 100%), respectively. Grade 3 to 4 toxicities consisted primarily of reversible hematologic or electrolyte abnormalities, including neutropenic fever in 18%. Conclusion TIP demonstrated efficacy as first-line therapy for intermediate- and poor-risk GCTs with an acceptable safety profile. Given higher rates of favorable response, progression-free survival, and overall survival compared with prior first-line studies, TIP warrants further study in this population.

scholarly journals Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia

Blood ◽  
2015 ◽  
Vol 125 (16) ◽  
pp. 2486-2496 ◽  
Author(s):  
Nathalie Dhédin ◽  
Anne Huynh ◽  
Sébastien Maury ◽  
Reza Tabrizi ◽  
Kheira Beldjord ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Key Points ◽  
First Complete Remission

Key Points SCT in first complete remission is associated with 69.5% 3-year overall survival in high-risk ALL adult patients treated with intensified pediatric-like protocol. Poor early MRD response is a powerful tool to select patients who may benefit from SCT in first complete remission.

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