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

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.

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Treatment of New Cases of Acute Promyelocytic Leukaemia by Arsenic Trioxide.

Blood ◽

10.1182/blood.v104.11.396.396 ◽

2004 ◽

Vol 104 (11) ◽

pp. 396-396 ◽

Cited By ~ 2

Author(s):

Ardeshir Ghavamzadeh ◽

Kamran Alimoghaddam ◽

Hamidolah Ghaffari ◽

Shahrano Rostami ◽

Yousef Mortazavi ◽

...

Keyword(s):

Complete Remission ◽

Arsenic Trioxide ◽

Induction Phase ◽

Line Treatment ◽

Rt Pcr ◽

First Line ◽

Common Cause ◽

One Year ◽

First Line Treatment

Abstract Purpose: Arsenic Trioxide approved for treatment of relapsed or refractory APL to ATRA. We studied the effects of Arsenic Trioxide as first line treatment of new cases of APL and their follow up. Material and methods: we studied 73 new cases of APL diagnosed by morphologic criteria and confirmed by cytogenetic, RT-PCR for PML/RARA and/or FISH and followed patients for MRD by sensitive nested RT-PCR. Our patients were 30 males and 43 females with median age 30+/− 12. Patients treated by infusion of 0.15mg/kg/d of Arsenic Trioxide to complete remission by morphologic criteria or till day +60. In patients who complete remission achieved, after 28 days rest, again we began Arsenic Trioxide 0.15mg/kg/d for 28 days as consolidation. Results: complete remission were achieved in 66 patients( 90.4%) and 7 early mortality. Median time to complete remission was 30+/−6.4 days. Most common cause of mortality was APL maturation syndrome ( 4 cases) Most common toxicities during induction phase were, APL maturation syndrome (10 cases), serositis(6 cases) and hepatotoxicity (19 cases). 63 cases(86.3%) are alive with a median follow up of 17+/−12.65 months. 14 relapses observed in our patients and complete remission achieved with re-treatment by Arsenic trioxide in 11 of them. Also we could control 3 fatal bleeding by infusion of activated factor 7(NovosevenÒ) which stopped hemorrhage . One year and two/three years survival of patients were 86% and 84%. Most common cause of death was APL maturation syndrome in 4 patients and relapse in 3 cases.Conclusion: Arsenic Trioxide is acceptable as first line treatment of APL and its result is comparable to ATRA with chemotherapy.

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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 ◽

10.1182/blood.v104.11.869.869 ◽

2004 ◽

Vol 104 (11) ◽

pp. 869-869 ◽

Cited By ~ 11

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.

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Arsenic Trioxide as First Line Therapy for New Case of APL, Results and Long Term Follow up.

Blood ◽

10.1182/blood.v114.22.1023.1023 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1023-1023

Author(s):

Ardeshir Ghavamzadeh ◽

Kamran Alimoghaddam ◽

Seyed Hamidolah Ghaffari ◽

Shahrbano Rostami ◽

Mohamad Jahani ◽

...

Keyword(s):

Arsenic Trioxide ◽

Early Mortality ◽

Line Treatment ◽

Rt Pcr ◽

Treatment Needs ◽

First Line ◽

Long Term Follow Up ◽

First Line Treatment

Abstract Abstract 1023 Poster Board I-45 Arsenic Trioxide approved for treatment of APL patients who relapsed after first line treatment failure by ATRA and chemotherapy. Its efficacy as first line treatment studied in at least three trials (including our center reports) previously. Here we are studying its efficacy, safety and long term follow up of new cases of APLwho treated by Arsenic trioxide without ATRA and/or Chemotherapy. Material and methods: between 1999 and 2009 we treated 190 new cases of APL by Arsenic Trioxide ( 0.15 mg/kg/day till CR ). Presence of t(15,17) confirmed in all cases by cytogenetic study and/or RT-PCR. In patients who achieved to CR we applied 4 more courses of daily ATO with the same dose for 28 days. Patients followed every 3 months by physical exam, hemogram and RT-PCR on peripheral blood for detection of relapse. Results: Median age of our patients was 29 years. Remission rate was 84.7% and median time to achieve to CR was 30 days. Median follow up was 37 months (maximum105 months) and for patients in remission, DFS was 73.4%. Also chance of 3 and 5 years DFS and OS were 71.3%, 83% and 67.6%, 72% respectively. Also Although early mortality was higher in patients with WBC more than 10000 at presentation, we couldn't find any significant correlation between DFS or OS and at presentation WBC count. Conclusion: Arsenic trioxide is effective as first line treatment of new cases of APL. Its long term results is comparable with conventional treatment of APL. optimization of treatment needs better supportive care to reduce early mortality due to APL differentiation syndrome and hemorrhagic episodes. Disclosures: No relevant conflicts of interest to declare.

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

Clinical Management Issues ◽

10.7175/cmi.v4i3.526 ◽

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.

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Oral Tetra-Arsenic Tetra-Sulfide Formula Versus Intravenous Arsenic Trioxide As First-Line Treatment of Acute Promyelocytic Leukemia: A Multicenter Randomized Controlled Trial

Journal of Clinical Oncology ◽

10.1200/jco.2013.48.8312 ◽

2013 ◽

Vol 31 (33) ◽

pp. 4215-4221 ◽

Cited By ~ 94

Author(s):

Hong-Hu Zhu ◽

De-Pei Wu ◽

Jie Jin ◽

Jian-Yong Li ◽

Jun Ma ◽

...

Keyword(s):

Arsenic Trioxide ◽

Acute Promyelocytic Leukemia ◽

Disease Free Survival ◽

Promyelocytic Leukemia ◽

Phase Iii ◽

Line Treatment ◽

First Line ◽

Multicenter Randomized Controlled Trial ◽

Noninferiority Margin ◽

First Line Treatment

Purpose This randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of an oral tetra-arsenic tetra-sulfide (As4S4) –containing formula named the Realgar-Indigo naturalis formula (RIF) compared with intravenous arsenic trioxide (ATO) as both induction and maintenance therapies for newly diagnosed acute promyelocytic leukemia (APL). Patients and Methods In all, 242 patients with APL were randomly assigned (1:1) to oral RIF (60 mg/kg) or ATO (0.16 mg/kg) combined with all-trans retinoic acid (ATRA; 25 mg/m2) during induction therapy. After achieving complete remission (CR), all patients received three courses of consolidation chemotherapy and maintenance treatment with sequential ATRA followed by either RIF or ATO for 2 years. The primary end point was the rate of disease-free survival (DFS) at 2 years, which was assessed for noninferiority with a 10% noninferiority margin. Results The median follow-up time was 39 months. DFS at 2 years was 98.1% (106 of 108) in the RIF group and 95.5% (107 of 112) in the ATO group. The DFS difference was 2.6% (95% CI, −3.0% to 8.0%). The lower limit of the 95% CI of DFS difference was greater than the −10% noninferiority margin, confirming noninferiority (P < .001). No significant differences were noted between the RIF and ATO groups with regard to the CR rate (99.1% v 97.2%; P = .62) or the overall survival at 3 years (99.1% v 96.6%; P = .18). The rates of adverse events were similar in the two groups. Conclusion Oral RIF plus ATRA is not inferior to intravenous ATO plus ATRA as first-line treatment of APL and may be considered as a routine treatment option for appropriate patients.

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A modified regimen of biweekly gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer is both tolerable and effective: a retrospective analysis

Therapeutic Advances in Medical Oncology ◽

10.1177/1758834016676011 ◽

2016 ◽

Vol 9 (2) ◽

pp. 75-82 ◽

Cited By ~ 28

Author(s):

Daniel H. Ahn ◽

Kavya Krishna ◽

Marlo Blazer ◽

Joshua Reardon ◽

Lai Wei ◽

...

Keyword(s):

Pancreatic Cancer ◽

Single Agent ◽

Progression Free Survival ◽

High Rate ◽

Drug Discontinuation ◽

Line Treatment ◽

First Line ◽

First Line Therapy ◽

Grade 3 ◽

First Line Treatment

Background: Treatment with nab-paclitaxel with gemcitabine demonstrates a survival advantage when compared with single-agent gemcitabine. However, the combination is associated with significant toxicities, leading to a high rate of drug discontinuation. We implemented a modified regimen of gemcitabine and nab-paclitaxel (mGNabP) in an attempt to minimize toxicities while maintaining efficacy. Methods: A total of 79 evaluable patients with metastatic pancreatic adenocarcinoma (mPC) treated with a modified regimen of gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) on days 1, 15 of every 28-day cycle were identified from our prospective database. A total of 57 patients received this regimen as first-line treatment and were evaluated for toxicities, progression-free survival (PFS), and overall survival (OS). Overall, 22 patients with advanced or metastatic PC treated with the modified regimen outside the first-line setting were only evaluated for toxicities. Results: The median OS and PFS were 10 months [95% confidence interval (CI) 5.9–13 months] and 5.4 months (95% CI 4.1–7.4 months) for patients that received the modified regimen as first-line therapy. Neurotoxicity occurred in 27% with only 1.6% of patients experiencing grade ⩾3 toxicity. The incidence of grade ⩾3 neutropenia was 19%, resulting in growth factor support in 12% of patients. This rate was similar in patients who received the modified regimen for first-line treatment of mPC versus the overall group. Conclusions: A modified regimen of biweekly nab-paclitaxel with gemcitabine is associated with a lower cost, acceptable toxicity profile and appears to be relatively effective in pancreatic cancer. Prospective randomized studies confirming its potential benefits compared with standard weekly mGNabP are warranted.

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Immune Checkpoint Inhibition in Oesophago-Gastric Carcinoma

Pharmaceuticals ◽

10.3390/ph14020151 ◽

2021 ◽

Vol 14 (2) ◽

pp. 151

Author(s):

Anica Högner ◽

Peter Thuss-Patience

Keyword(s):

Cell Death ◽

Gastric Carcinoma ◽

Programmed Cell Death ◽

Immune Checkpoint ◽

Disease Free Survival ◽

Line Treatment ◽

Second Line ◽

First Line ◽

The Usa ◽

First Line Treatment

Immune checkpoint inhibitors enrich the therapeutic landscape in oesophago-gastric carcinoma. With regard to oesophageal squamous cell carcinoma (ESCC), the selective PD-1 (programmed cell death receptor 1)-inhibitor nivolumab improves disease-free survival in the adjuvant therapy setting (CHECKMATE-577). In first-line treatment, ESCC patients (pts) benefit in overall survival (OS) from the PD-1-inhibitor pembrolizumab in combination with chemotherapy (KEYNOTE-590). In the second-line setting, nivolumab (ATTRACTION-03) and pembrolizumab (KEYNOTE-181) demonstrate a benefit in OS compared with chemotherapy. These data resulted in the approval of nivolumab for the second-line treatment of advanced ESCC pts regardless of PD-L1 (programmed cell death ligand 1) status in Europe, Asia, and the USA, and pembrolizumab for pts with PD-L1 CPS (combined positivity score) ≥ 10 in Asia and the USA. Further approvals can be expected. In gastro-oesophageal junction and gastric cancer, the addition of nivolumab to chemotherapy in first-line treatment improves OS in pts with advanced disease with PD-L1 CPS ≥ 5 (CHECKMATE-649). Additionally, pembrolizumab was non-inferior to chemotherapy for OS in PD-L1 CPS ≥ 1 pts (KEYNOTE-062). In third-line treatment, nivolumab shows benefits in OS regardless of PD-L1 expression (ATTRACTION-02) with approval in Asia, and pembrolizumab prolonged the duration of response in PD-L1 positive pts (KEYNOTE-059) with approval in the USA. We discuss the recent results of the completed phase II and III clinical trials.

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Efficacy of Coenzyme Q10 in the Treatment of Cyclic Vomiting Syndrome in Children

10.26420/jpediatrchildhealthcare.2021.1038 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Brezin F ◽

◽

Wiedemann A ◽

Bansept C ◽

Albuisson E ◽

...

Keyword(s):

Coenzyme Q10 ◽

Gastrointestinal Disorder ◽

Cyclic Vomiting Syndrome ◽

Line Treatment ◽

First Line ◽

Excellent Safety Profile ◽

Third Line ◽

One Year ◽

First Line Treatment ◽

Cyclic Vomiting

Cyclic Vomiting Syndrome (CVS) is a chronic functional gastrointestinal disorder related to migraine, characterized by episodic nausea and vomiting. The treatment of CVS remains based on tricyclic antidepressants, triptans and antiepileptics. As mitochondriopathy has been involved in the pathophysiology of CVS, Coenzyme Q10 (CoQ10), a mitochondrial cofactor, has been used as the third line treatment in CVS. Considering the excellent safety profile of CoQ10, we decided to use it as the first line treatment in CVS. We retrospectively studied the evolution of 23 CVS patients who were treated for one year by CoQ10 alone. We recorded the characteristics of patients and their CVS history and compared data obtained the year before and the year following the prescription of CoQ10 treatment. We found a significant decrease in the number of vomiting episodes between the year before and the year after the start of CoQ10 (median [IQR]: 18.0 [15.75] vs. 3.00 [5.0]; p <0.001). This decrease persisted with time (2 and 3 years of treatment). The treatment was very efficient in 17/23 patients and did not decrease the number of vomiting episodes in 3 patients. Only one mild side effect related to the drug has been reported. Conclusions: CoQ10 is an efficient and safe treatment of CVS and should be used as the first line treatment in this episodic syndrome related to migraine.

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

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2016.062 ◽

2016 ◽

Vol 8 ◽

pp. e2016062 ◽

Cited By ~ 1

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.

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

Cancers ◽

10.3390/cancers12040773 ◽

2020 ◽

Vol 12 (4) ◽

pp. 773 ◽

Cited By ~ 2

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.

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