A Phase 2 Evaluation of Single Agent Clofarabine as First Line Treatment for Older Patients with AML Who Are Not Considered Fit for Intensive Chemotherapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 869-869 ◽  
Author(s):  
Alan K. Burnett ◽  
Nigel Russell ◽  
Jonathan W. Kell ◽  
Donald Milligan ◽  
Dominic Culligan
Keyword(s):  
Complete Remission ◽  
Older Patients ◽  
Liver Toxicity ◽  
Single Agent ◽  
Randomised Trial ◽  
Significant Proportion ◽  
Intensive Chemotherapy ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

Abstract Patients over 70 years represent a significant proportion of patients with AML. They respond poorly to intensive chemotherapy. Although 50% of patients can achieve CR, only 8% are alive at 2 years (MRC Database). In addition significant numbers of these patients either do not wish to undergo, or are not considered fit for intensive chemotherapy. This represents a significant unmet medical need. Nucleoside analogues (Ara-C) provide an active group of agents in AML, Fludarabine however is ineffective at tolerable doses. Clofarabine has been modified by introducing a Fluorine in the 2′ position which confers reduced susceptibility to cleavage of the glycosidic linkage and also reduced toxicity caused by halogenated nucleobases. As such the drug has potential use as an oral formulation. Previous clinical and in vitro studies have established a dose schedule at 40mg/m2 days 1–5. This is associated with CRs in relapse/refractory AML, but with grade ¾ liver toxicity in 25% of patients. Because of these characteristics we undertook a non-randomised study using a dose of 30mg/m2 days 1-5 IV, which could be repeated for up to 4 courses at a minimum of 28 days apart. The target patient group were patients >70 years, or patients 60–70 with a cardiac history, who were not considered fit for conventional chemotherapy. Twenty-eight patients entered the study: 16 males, 12 females of a median age 71 years (range 60 – 79). The FAB distribution was, M0=1;M1=9; M2=8; M4=2; M5=4; M6=3; Unknown=1. The cytogenetic risk group (MRC criteria) were 26 standard and 2 unfavourable risk. All patients received course 1. Five patients died before response could be assessed from causes which were not thought to be associated with the drug. One patient is too early to assess response. Five did not enter complete remission although there was a reduction in bm blasts from 58 to 18%, 55 to 20% and 30 to 15% in 3 cases. Sixteen patients (59%) achieved complete remission after course 1. Grade 3 toxicity was seen in 3 patients, but this recovered in all cases in a few days. Patients who did not enter CR did not show haematological recovery after course 1 and were considered treatment failures. Of the 16 patients who entered CR, haematological recovery to ANC 1.0 x 109/l took 28 days (range 21–42) Platelets to 50x109/l took 25 days (range 21–38). Conclusions: Clofarabine is an active agent when used alone as first line treatment. It is well tolerated but is associated with cytopenia of an average 28 days. At the dose chosen for this study grade ¾ liver toxicity was uncommon. The drug is a candidate for evaluation in a randomised trial and/or in combination schedules, and lower doses should be explored in older patients. This study was partially supported by an unrestricted grant from Bioenvison Inc.

scholarly journals Outcome of Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia before Second-Generation FLT3 Tyrosine Kinase Inhibitors: A Toulouse–Bordeaux DATAML Registry Study

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 773 ◽  
Author(s):  
Sarah Bertoli ◽  
Pierre-Yves Dumas ◽  
Emilie Bérard ◽  
Laetitia Largeaud ◽  
Audrey Bidet ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Response Rate ◽  
Intensive Chemotherapy ◽  
Line Treatment ◽  
First Line ◽  
Low Intensity ◽  
First Line Treatment ◽  
Acute Myeloid

A recent phase 3 trial showed that the outcome of patients with relapsed/refractory (R/R) FLT3-mutated acute myeloid leukemia (AML) improved with gilteritinib, a single-agent second-generation FLT3 tyrosine kinase inhibitor (TKI), compared with standard of care. In this trial, the response rate with standard therapy was particularly low. We retrospectively assessed the characteristics and outcome of patients with R/R FLT3-mutated AML included in the Toulouse–Bordeaux DATAML registry. Among 347 patients who received FLT3 TKI-free intensive chemotherapy as first-line treatment, 174 patients were refractory (n = 48, 27.6%) or relapsed (n = 126, 72.4%). Salvage treatments consisted of intensive chemotherapy (n = 99, 56.9%), azacitidine or low-dose cytarabine (n = 9, 5.1%), other low-intensity treatments (n = 17, 9.8%), immediate allogeneic stem cell transplantation (n = 4, 2.3%) or best supportive care only (n = 45, 25.9%). Among the 114 patients who previously received FLT3 TKI-free intensive chemotherapy as first-line treatment (refractory, n = 32, 28.1%; relapsed, n = 82, 71.9%), the rate of CR (complete remission) or CRi (complete remission with incomplete hematologic recovery) after high- or low-intensity salvage treatment was 50.0%, with a bridge to transplant in 34.2% (n = 39) of cases. The median overall survival (OS) was 8.2 months (interquartile range, 3.0–32); 1-, 3- and 5-year OS rates were 36.0% (95%CI: 27–45), 24.7% (95%CI: 1–33) and 19.7% (95%CI: 1–28), respectively. In this real-word study, although response rate appeared higher than the controlled arm of the ADMIRAL trial, the outcome of patients with R/R FLT3-mutated AML remains very poor with standard salvage therapy.

First-line treatment of acute promyelocytic leukemia with arsenic trioxide without ATRA and chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7073-7073
Author(s):  
A. Ghavamzadeh ◽  
K. Alimoghaddam ◽  
S. Ghaffari ◽  
S. Rostami ◽  
M. Jahani ◽  
...  
Keyword(s):  
Complete Remission ◽  
Arsenic Trioxide ◽  
Single Agent ◽  
Disease Free Survival ◽  
Early Mortality ◽  
Line Treatment ◽  
First Line ◽  
First Line Therapy ◽  
One Year ◽  
First Line Treatment

7073 Background: Standard treatment of APL is ATRA plus chemotherapy but Arsenic Trioxide (ATO) is most potent single agent against APL cells. Role of ATO in first line therapy of APL needs to clarify. Methods: Between may 2000 and September 2006,we treated 141 new cases of APL(Median age 28±12.8 y/o min=11,max=71) by 2 hours iv infusion of 0.15mg/kg ATO until complete remission. Trial approved by IRB and consent form obtained. Diagnosis was by clinical and morphologic characteristics and confirmed by cytogenetic and RT-PCR for detection of t(15,17) and presence of PML-RARa. After complete remission patients received consolidation by 28 days infusion of ATO for one or four courses.(one consolidation one month after CR and for some patients second, third and forth consolidations one month after first one and two another , one year and two year after CR) Results: : complete remission observed in 121 cases(85.8%) and early mortality rate was14.9%(most common cause of early mortality was APL syndrome,61.9%).Median follow up was 28 months. For patients who achieve to complete remission,one, two and three year disease free survival were 95.6%± 2%, 76.9±4% and 57± 6%,respectively. Many relapsed patients salvaged again with ATO alone so, two and three years overall survival for this cohort was 95.6%±2% and 83.7%±4%. Increasing number of consolidation from one to four couldn’t increase DFS or OS in one and two years after CR. Conclusions: ATO is effective in treatment of new cases of APL. Introduction of ATO in first line treatment of APL(with or without ATRA plus chemotherapy) needs a multi center randomized clinical trial. No significant financial relationships to disclose.

scholarly journals Current problems in the first-line treatment of metastatic breast cancer: focus on the role of docetaxel

2010 ◽  
Vol 4 (3) ◽  
pp. 97-107
Author(s):  
Filippo Montemurro
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Complete Remission ◽  
Liver Metastases ◽  
Single Agent ◽  
Metastatic Breast ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

Metastatic breast cancer is a very heterogeneous disease, both from a clinical and a biological point of view. Despite being still incurable, the expanding therapeutic repertoire has determined a progressive increase in median survival. We describe the clinical course of a 67-year-old woman with a locally advanced, hormone-receptor positive breast cancer with synchronous liver metastases. Single-agent docetaxel at the dose of 100 mg/m2 for 8 cycles determined a pathological complete remission in the breast and a near complete remission of liver metastases. After more than 4 years from diagnosis, the patient is alive and without signs of tumour progression. Based on this clinical case, we discuss management issues like the choice of the initial treatment, the use of monochemotherapy vs polychemotherapy, the worth of surgery of the primary tumour in patients with stage IV disease, and the issue of maintenance endocrine therapy. Furthermore, we reviewed the pivotal role of docetaxel in the management of advanced breast cancer. Whether monochemotherapy or polychemotherapy is felt to be an adequate choice in the clinical practice, docetaxel qualifies as one of the most active and manageable agents. Single agent activity ranging from 20-48% in terms of response rate has been reported in several clinical trials in patients treated in various clinical settings. Docetaxel-based combinations with other cytotoxic agents have become established in the first line treatment both in patients with anthracycline-resistant and anthracycline-sensitive metastatic breast cancer. Finally, docetaxel has been shown to be an optimal companion drug for biologically targeted agents like trastuzumab or bevacizumab, resulting in further treatment options.

Praktijkadvies rond de aanpak van anafylaxie bij (Covid-19-)vaccinatie bij kwetsbare ouderen (incl. e-learning)

2021 ◽  
Author(s):  
E. DUYVER ◽  
T. VAN DE VELDE ◽  
D. RAZOOQI ◽  
K. VERSLUYS ◽  
M. PETROVIC ◽  
...  
Keyword(s):  
Older People ◽  
Older Patients ◽  
Large Scale ◽  
Vaccination Campaign ◽  
Line Treatment ◽  
First Line ◽  
Practical Advice ◽  
E Learning ◽  
Treatment Education ◽  
First Line Treatment

Practical advice on the anaphylaxis policy for (COVID-19) vaccination in frail, older patients In view of the imminent start of the COVID-19 vaccination campaign, a practical advice based on the available literature on anaphylaxis in older people was drawn up for use in frail, older patients. The present practical advice provides guidance with regard to the diagnosis of anaphylaxis, the first-line treatment, education and necessary material with the purpose of making nursing homes and vaccination centres well prepared for the large-scale COVID-19 vaccination.

scholarly journals SYSTEMIC FRONT LINE THERAPY OF FOLLICULAR LYMPHOMA: WHEN, TO WHOM AND HOW

2016 ◽  
Vol 8 ◽  
pp. e2016062 ◽  
Author(s):  
Francesca Pavanello ◽  
Sara Steffanoni ◽  
Michele Ghielmini ◽  
Emanuele Zucca
Keyword(s):  
Monoclonal Antibodies ◽  
Follicular Lymphoma ◽  
Target Therapy ◽  
Single Agent ◽  
New Drugs ◽  
Response To Treatment ◽  
Line Treatment ◽  
First Line ◽  
Line Therapy ◽  
First Line Treatment

The natural history of follicular lymphoma is usually characterized by an indolent course with a high response rate to the first line therapy followed by recurrent relapses, with a time to next treatment becoming shorter after each subsequent treatment line. More than 80% of patients have advanced stage disease at diagnosis. The time of initiation and the nature of the treatment is mainly conditioned by symptoms, tumor burden, lymphoma grading, co-morbidities and patients preference. A number of clinical and biological factors have been determined to be prognostic in this disease, but the majority of them could not show to be predictive of response to treatment, and therefore can’t be used to guide the treatment choice. CD20 expression is the only predictive factor recognized in the treatment of FL and justifies the use of “naked” or “conjugated” anti-CD20 monoclonal antibodies as single agent or in combination with chemo- or targeted therapy. Nevertheless, as this marker is almost universally found in FL, it has little role for the choice of treatment. The outcome of patients with FL improved significantly in the last years, mainly due to the widespread use of rituximab, autologous and allogeneic transplantation in young and fit relapsed patients, the introduction of new drugs and the improvement in diagnostic accuracy and management of side effects. Agents as new monoclonal antibodies, immuno-modulating drugs and target therapy have recently been developed and approved for the relapsed setting, while studies to evaluate their role in first line treatment are still ongoing. Here we report our considerations on first line treatment approach and on the potential factors which could help in the choice of therapy.

Clarithromycin Leading to Complete Remission in the First-Line Treatment of Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma

2015 ◽  
Vol 33 (35) ◽  
pp. e130-e132 ◽  
Author(s):  
Barbara Kiesewetter ◽  
Julius Lukas ◽  
Andreas Kuchar ◽  
Marius E. Mayerhoefer ◽  
Leonhard Müllauer ◽  
...  
Keyword(s):  
Complete Remission ◽  
Lymphoid Tissue ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment
Sign in / Sign up

Export Citation Format

Share Document