DTIC and GM-CSF in the treatment of patients with metastatic melanoma.

e19045 Background: To describe patients with metastatic melanoma being treated with mono-therapy, dacarbazine (DTIC) or granulocyte-macrophage colony-stimulating factor (GM-CSF). Methods: Using a large U.S. medical claims database, patients were identified between 2005 and 2010 using ≥2 melanoma diagnoses (ICD-9-CM: 172.xx, V10.82) and ≥2 diagnoses for metastasis (ICD-9-CM: 197.xx, 198.xx). Patients who received mono-therapy with DTIC or GM-CSF as the first documented drug therapy after metastatic diagnosis were identified. Patient demographic and clinical characteristics and treatment duration were compared between patients treated with DTIC and those who received GM-CSF. Furthermore, comparisons were also made between the two treatment groups after 1-to-1 matching on age, gender, and baseline comorbidities. Results: A total of 81 patients with metastatic melanoma receiving first-line DTIC and 24 patients with metastatic melanoma receiving first-line GM-CSF were included in this analysis. On average, DTIC patients were 8.5 years older (p = 0.009) and had higher baseline Charlson Comorbidity Index scores (D0.43, p = 0.005) than GM-CSF patients. The mean duration of first line treatment was 94 days on DTIC and 135 days on GM-CSF. The mean length of follow-up from the start of first line was 257 days on DTIC and 451 days on GM-CSF. After each GM-CSF patient was matched with a DTIC patient on age, gender, and baseline Charlson Comorbidity Index score, the mean duration of first line treatment was 79 days on matched DTIC and 135 days on GM-CSF, and the mean length of follow-up from the start of first line was 317 days on matched DTIC and 451 days on GM-CSF. Conclusions: Patients with metastatic melanoma who received DTIC treatment were older and had higher comorbidity index scores but shorter treatment duration than those who received GM-CSF; the difference in treatment duration remained after DTIC patients were matched with GM-CSF patients on age, gender and comorbidity index scores.

Download Full-text

Aplastic Anemia in the Elderly: A Nationwide Survey on Behalf of the French Reference Center for Aplastic Anemia

Blood ◽

10.1182/blood-2018-99-113359 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1298-1298

Author(s):

Adrien Contejean ◽

Matthieu Resche-Rigon ◽

Jérôme Tamburini ◽

Marion Alcantara ◽

Fabrice Jardin ◽

...

Keyword(s):

Aplastic Anemia ◽

Charlson Comorbidity Index ◽

Research Funding ◽

Performance Status ◽

Line Treatment ◽

First Line ◽

Advisory Committees ◽

Comorbidity Index ◽

Grade Iii ◽

First Line Treatment

Abstract Introduction Aplastic anemia (AA) is a rare but potentially life-threatening disease that frequently occurs in older patients. Various therapeutic options can be proposed and data regarding the ideal first line treatment of AA in this ageing population remains scarce. Methods We conducted a retrospective nationwide multicenter study in France to examine current treatments for AA patients over 60 years old within a 10-year period (1/1/2007 to 12/31/2016). Our aims were to evaluate efficacy and tolerance of AA treatment, and to analyze predictive factors for response and survival. Patients who were diagnosed with AA by a bone marrow biopsy at the age of 60 or over were included in the study. Results Over the course of a decade, 88 patients (median age 68.5) were identified in 19 centers, with a median follow-up of 32.1 months; 49% were women, the median Charlson comorbidity index was 2 (range 0-6), the median performance status was 1 (range 0-3), 21% had very severe (vSAA) and 36% severe AA. We analyzed 184 treatment lines which comprised ATG-CsA (33%, including 72% with horse ATG), CsA alone (14%), androgen alone (14%), eltrombopag alone (10%), CsA associated with androgen or eltrombopag (9%), and other treatments (20%). First-line treatment was ATG-CsA for half of patients. Comparisons of patients treated in first line with ATG-CsA, CsA or other treatments revealed that patients receiving ATG-CsA were significantly younger (66 years, vs. 71.5 vs. 71.5, respectively, p=0.007), more frequently female (61%, vs. 50% vs. 27%, p=0.02) and had a lower platelet count (8x109/L, vs. 12x109/L vs. 15x109/L, p=0.025). We found no difference with respect to weight, Charlson comorbidity index score, performance status or disease severity between first line treatment regimens. After first-line therapy, 32% of patients achieved a complete response (CR), and 15% a partial response (PR). After the 181 assessable treatment lines, 19% achieved CR and 19% a PR. Median time until best response was 151 days. The overall response rate (ORR) was 62% with ATG-CsA (70% as a first-line treatment), 35% with CsA alone (39% as first-line), 22% with eltrombopag, and 21% with androgen. The ORR in patients over 70 years receiving ATG-CsA (n=16) was 81% (50% achieving a CR). Responses were significantly better in first line and in patients with good performance status, as well as in those that had received ATG-CsA (ORR of 70% after first-line treatment). In a multivariable analysis using ATG-CsA as a baseline, we found that CsA alone (OR 0.35 (0.13;0.96), p=0.042), eltrombopag (OR 0.12 (0.03;0.54), p=0.0057) and androgens (OR 0.17 (0.05;0.58), p=0.0047) were all individually associated with lower response rates. The main complications were infections (grade III/IV, 35% of treatment lines including 9 deaths (5%)), and renal issues (grade-III/IV, 29%). ATG-CsA was associated with significantly more infectious complications (72% vs. 24%, p<0.0001), cardiovascular complications (32% vs. 15%, p=0.01) and acute kidney failure (43% vs. 22%, p=0.003) than other treatments. Patients aged 70 and over receiving ATG-CsA did not experience more complications than younger patients. Four clonal evolutions were recorded: two abnormal karyotypes (1 monosomy of chromosome 7 and 1 t(3;4)), one case of acute myeloid leukemia, and one case of myelodysplastic syndrome with 17% excess blasts. Three-year survival was 74.7% (median survival 7.36 years, Figure) and 24 patients died (nine infections, five deaths in palliative care or after active treatment had finished, four hemorrhagic complications, and six miscellaneous causes). Age (OR 1.07 (1.01;1.14), p=0.03), Charlson comorbidity index (HR 1.34 (1.07;1.67), p=0.01) and vSAA (HR 3.67 (1.51;8.91), p=0.004) were independently associated with mortality. Conclusion Our study showed a significantly better ORR with ATG-CsA than other regimens for treatment of AA in elderly, with more complications but no more death. Age per se is not a limiting factor for treatment with ATG-CsA: this regimen should be used as first-line treatment in elderly patients if they have a good performance status and low comorbidity index score. Among patients with adverse performance status or comorbidities contra-indicating the use of ATG, CsA alone or in combination may be safely used. Other strategies might be reserved for later courses of treatments. Supportive care may have a great impact on survival in this population. Disclosures Ades: JAZZ: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; silent pharma: Consultancy; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Peffault De Latour:Pfizer Inc.: Consultancy, Honoraria, Research Funding; Amgen Inc.: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding.

Download Full-text

Sotalol as first-line treatment for fetal tachycardia and neonatal follow-up

Ultrasound in Obstetrics and Gynecology ◽

10.1002/uog.12390 ◽

2013 ◽

Vol 42 (3) ◽

pp. 285-293 ◽

Cited By ~ 19

Author(s):

L. B. van der Heijden ◽

M. A. Oudijk ◽

G. T. R. Manten ◽

H. ter Heide ◽

L. Pistorius ◽

...

Keyword(s):

Line Treatment ◽

First Line ◽

Fetal Tachycardia ◽

First Line Treatment

Download Full-text

6085 FOLFOXIRI (irinotecan, oxaliplatin, infusional 5FU/LV) vs FOLFIRI as first-line treatment of metastatic colorectal cancer (mCRC): updated results after 5 years follow up and risk-stratified analysis

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(09)71180-2 ◽

2009 ◽

Vol 7 (2) ◽

pp. 348

Author(s):

A. Falcone ◽

G. Masi ◽

E. Vasile ◽

F. Loupakis ◽

S. Cupini ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Line Treatment ◽

First Line ◽

Stratified Analysis ◽

First Line Treatment

Download Full-text

PS01.095: BENIGN ESOPHAGEAL STRICTURE: A RECAP OF OUR EXPERIENCE

Diseases of the Esophagus ◽

10.1093/dote/doy089.ps01.095 ◽

2018 ◽

Vol 31 (Supplement_1) ◽

pp. 76-76

Author(s):

Keat How Teoh ◽

Kelvin Voon ◽

Shyang Yee Lim ◽

Premnath Nagalingam

Keyword(s):

Endoscopic Treatment ◽

Esophageal Stricture ◽

Endoscopic Dilatation ◽

Line Treatment ◽

First Line ◽

Benign Esophageal Stricture ◽

Anastomotic Strictures ◽

Esophageal Strictures ◽

The Mean ◽

First Line Treatment

Abstract Background Caustic injury remains the commonest cause of benign esophageal strictures in Asia. Others include gastroesophageal reflux, iatrogenic, radiation, autoimmune or idiopathic causes. Treatment goals are relief of dysphagia and prevention of recurrence. This study aims to evaluate the experience with benign esophageal stricture in Penang Hospital, a tertiary hospital in Northern region of Malaysia. Methods A retrospective review of 12 patients with benign esophageal strictures between year 2012 - 2017. Results The mean age was 53.5 and two thirds were female. Half of these patients were of Chinese ethnicity while the other half were Indian. The commonest cause was caustic ingestion (41.7%), followed by reflux stricture (25%) and anastomotic stricture (25%). There was one case of dystrophic epidermolysis bullosa. More than half of the patients had complex and multiple strictures. 41.7% of patients had proximal strictures that were located within 20cm from the incisors. Endoscopic dilatation was the first line treatment with either Savary Gilliard or balloon dilators. A total of 97 dilatation sessions were done with a mean dilatation frequency of 2.3 ± 1.5 times for anastomotic strictures, 8 ± 8.2 times for reflux strictures and 8.0 ± 6.6 times for corrosive strictures. The mean dilatation interval was 2.5 ± 1.2 weeks. 58.3% of patients had successful endoscopic treatment. The success rate was higher in non-corrosive stricture (83% vs 40%). There was one dilatation related complication in which the patient had pneumomediastinum without overt mediastinitis. This however, resolved with conservative management. 41.7% of patients had refractory strictures that failed endoscopic dilatation. Surgery including esophagectomy (40%), revision of anastomosis (20%) and gastrostomy (40%) were done for this group of patients. Proximal strictures, complex strictures and multiple strictures were associated with failed endoscopic dilatation (P < 0.05). Conclusion Endoscopic dilatation is the first line treatment for benign esophageal strictures. Surgery is reserved for refractory strictures with failed endoscopic treatment. Predictor scoring systems for refractory stricture and individualized approaches are the key to success. Disclosure All authors have declared no conflicts of interest.

Download Full-text

Clinical and Biological Characteristics and Outcomes of Richter Transformation : A French Multicenter Study from the Filo Group

Blood ◽

10.1182/blood-2019-128053 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4112-4112

Author(s):

Charline Moulin ◽

Romain Morizot ◽

Thomas Remen ◽

Hélène Augé ◽

Florian Bouclet ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Intermediate Risk ◽

Line Treatment ◽

First Line ◽

Advisory Committees ◽

Long Term Survivors ◽

First Line Treatment

Introduction: About 2 to 10% of patients (pts) diagnosed with Chronic Lymphocytic Leukemia (CLL) develop diffuse large B-cell lymphoma (DLBCL, so-called Richter transformation (RT)) over long-term follow-up. The outcomes of pts with RT are variable and poorly understood and there is no consensus on the best therapeutic approach. The aim of this study was to analyze the clinical characteristics, outcomes and factors predictive of survival in a large series of RT from the French Innovative Leukemia Organization (FILO). Methods: Biopsy-confirmed RT (limited to DLBCL and excluding Hodgkin lymphoma) diagnosed from 2001 to 2018 were identified from eight FILO centers. Clinical and biological characteristics of CLL and RT at diagnosis, including cytogenetics, clonal relation with the pre-existing CLL, Epstein-Barr virus (EBV) status, cell of origin (COO) analyzed by immunohistochemistry and RT score (Tsimberidou AM et al, J Clin Oncol, 2006) were analyzed as well as treatment and outcomes. Overall survivals (OS) were defined as time from CLL and RT diagnosis to death from any cause and analyzed using the Kaplan-Meier method. Statistical analyses were performed with SAS version 9.4. Results: A total of 70 CLL pts who developed RT were identified. The median age at CLL diagnosis was 62 years old (range 35-82), and 50 (71.4 %) were male. The median time to transformation was 5.5 years (range 0 to 22 years), with 12 simultaneous diagnosis of CLL and RT. Prior to RT, 20 (29%) pts had not been treated for CLL, 50 received one (n=21) or more (n= 29) line of treatment ; 6 pts had received a novel agent (ibrutinib, idelalisib or venetoclax). The median age at RT diagnosis was 68 years old (range 42-88). All biopsies were centrally reviewed; 38/58 pts (66%) had elevated LDH (>1.5N) ; 35/65 pts (54 %) had bulky disease (≥ 5 cm); 10/54 (18.5%) pts had del(17p) or TP53 mutation ; 9/42 pts (21%) had a complex karyotype (at least 3 abnormalities). The CLL and RT were clonally related in 27/27 (100%) tested pts. COO by Hans algorithm was non germinal center B cell-like (GCB) in 26/28 pts (93%). EBV was positive or detected in 5/40 (12.5%) pts. The median of Ki67 positivity was 70% (range 30% to 100%). The RT score (based at RT diagnosis on ECOG performance status 2-4, LDH >1.5 x normal, platelets<100 x 109/L, tumor size >5 cm and >1 prior therapy for CLL) was : low risk in 17 pts (31%), low-intermediate risk in 10 pts (19%), high-intermediate risk in 14 pts (25%) and high risk in 14 pts (25%). The most common first-line treatment of RT was immunochemotherapy (n=57, 87%) including R-CHOP-like regimen (n=48, 73%). Autologous or allogeneic transplantation was performed for 7 pts (11%). Response to first-line treatment was complete or partial response in 26 pts (40%), and stable disease or progression in 39 pts (60%). After a median follow-up of 8 years, 51/64 pts (80%) have died. The main causes of death were progressive DLBCL (n=36, 71%), infection (n=8, 16%) or progressive CLL (n=2, 4%). The median OS of the cohort from CLL and RT diagnosis (Figure 1) were 7.8 years and 9.5 months, respectively. In univariate analysis, patients with TP53 disruption at CLL stage, low platelets count, elevated LDH, elevated beta2-microglobulin, high ECOG score, high RT score, EBV positivity and absence of response to first-line RT treatment had worse OS. The ECOG score, platelets count and TP53 disruption remain significant in multivariate Cox-regression. Last, we compared the clinical and biological parameters of two Richter groups defined as: (i) short-term survivors (<12 months, n = 34) and (ii) long-term survivors (>48 months, n = 18). Long survival was significantly associated with elevated platelets count, low LDH, low ECOG, low RT score and response to RT first-line treatment. Discussion: The clinical outcomes of RT patients is poor and novel treatment options are needed. However, a group of long-term survivors was identified, characterized by elevated platelets count, low LDH, low ECOG, low RT score and response to immunochemotherapy. Disclosures Leblond: Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Thieblemont:Roche: Honoraria, Research Funding; Gilead: Honoraria; Novartis: Honoraria; Kyte: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Cellectis: Membership on an entity's Board of Directors or advisory committees. Cymbalista:Janssen: Honoraria; Gilead: Honoraria; AstraZeneca: Honoraria; Sunesis: Research Funding; Roche: Research Funding; Abbvie: Honoraria. Guièze:Abbvie: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Roche: Honoraria. Broseus:Janssen: Honoraria; Gilead: Honoraria; Novartis: Research Funding. Feugier:gilead: Honoraria, Research Funding, Speakers Bureau; janssen: Honoraria, Research Funding, Speakers Bureau; abbvie: Honoraria, Research Funding, Speakers Bureau; roche: Honoraria, Research Funding, Speakers Bureau.

Download Full-text

Efficacy of Two-Week Therapy with Doxycycline-Based Quadruple Versus Levofloxacin Concomitant for Helicobacter Pylori Infection: A Prospective Single-Center Randomized Controlled Trial.

10.21203/rs.3.rs-457018/v1 ◽

2021 ◽

Author(s):

Marouf Alhalabi ◽

Waleed Alassi ◽

Kamal Alaa Eddin ◽

Khaled Cheha

Keyword(s):

Helicobacter Pylori ◽

Odds Ratio ◽

Controlled Trial ◽

Helicobacter Pylori Infection ◽

Line Treatment ◽

First Line ◽

Open Label ◽

Randomized Controlled ◽

First Line Treatment

Abstract Background: Antibiotic-resistant reduces the efficacy of conventional triple therapy for Helicobacter Pylori infections worldwide, lead to varying treatment protocols according to locations. This was an open‑label randomized controlled trial. We used two protocols, doxycycline-based quadruple and concomitant levofloxacin regimens. The aim was to compare the eradication rates of previous protocols as empirical first-line treatment to cure Helicobacter Pylori infection in intention-to-treat (ITT) and per-protocol analyses (PPA) in Syrian population.Settings and Design: an open‑label parallel randomized controlled trial.Methods: We randomly assigned seventy-eight naïve who tested positive for Helicobacter Pylori gastric infection, with a 1:1 ratio to (D-group ) which receive (bismuth subsalicylate 524 mg four times daily, doxycycline 100 mg, tinidazole 500 mg, and esomeprazole 20 mg, each twice per day for two weeks), or (L-group) which receive (levofloxacin 500 mg daily, tinidazole 500 mg, amoxicillin 1000 mg, and esomeprazole 20 mg each twice per day for two weeks). We confirmed Helicobacter Pylori eradication by stool antigen test at eight weeks. Results: Thirty-nine patients were allocated in each group. In the D-group, thirty-eight patients completed the follow-up, thirty patients were cured. While in the L-group, thirty-nine completed the follow-up, thirty-two patients were cured. According to ITT, the eradication rates were 76.92%, and 82.05%, for the D-group and L-group respectively. Odds ratio with 95% confidence interval was 1.371 [0.454-4.146]. According to PPA, the eradication rates were 78.9 %, and 82.05% for the D-group and L-group respectively. The odds ratio with 95% confidence interval was 1.219 [0.394-3.774]. We didn’t report serious adverse effects. Conclusions: The eradication rates in both therapy regimes were fair. Further researches are required to identify the optimum first-line treatment for Helicobacter-Pylori Infection in the Syrian population.Trial registration: We register this study as a standard randomized clinical trial (Clinicaltrial.gov, identifier‑NCT04348786, date:29-January-2020, https://clinicaltrials.gov/ct2/show/NCT04348786).

Download Full-text

Predictive value of systematic inflammatory response biomarkers (NLR, LMR, PLR) in patients with ovarian cancer.

Diagnostyka Laboratoryjna ◽

10.5604/01.3001.0013.7974 ◽

2017 ◽

Vol 53 (3) ◽

pp. 139-146

Author(s):

Urszula Rychlik ◽

Ewa Wójcik ◽

Jadwiga Tarapacz ◽

Katarzyna Brandys ◽

Zofia Stasik ◽

...

Keyword(s):

Ovarian Cancer ◽

Complete Response ◽

Response To Treatment ◽

Line Treatment ◽

First Line ◽

Lymphocyte Ratio ◽

Lymphocyte To Monocyte Ratio ◽

Progression Of Disease ◽

First Line Treatment

Introduction: The aim of the study was to assess the prognostic value of indicators calculated on the basis of initial hematology test results of neutrophil, lymphocyte, monocyte and platelet counts (NLR – neutrophil-to-lymphocyte ratio, LMR – lymphocyte-to-monocyte ratio, PLR – platelet-to-lymphocyte ratio) in patients with ovarian cancer and their compliance with the overall response to treatment. Materials and methods: Hematological tests were performed before first course of first-line chemotherapy in 145 patients with ovarian cancer. Response to treatment was assessed according to the RECIST1.1 criteria in all patients. Results: After the completion of first-line treatment, 70 (48.3%) patients had a complete response (CR) to the therapy. In this group, progression of disease occurred in 22 (31.4%) patients during 12 months of follow-up. In the CR group with progression, 17 (77.2%) presented high NLR and PLR levels. Among 48 (68.6%) patients with CR without progression after 12 months of follow-up, high levels of NLR and PLR were observed in 21 (43.8%) and 17 (35.4%) of them, respectively. Low LMRs were observed in 16 (72.7%) patients with progression and 16 (33.3%) without progression. Conclusion: High levels of NLR and PLR and low levels of LMR before treatment seems to predict 12-month disease progression in patients with complete response to first-line treatment.

Download Full-text