Amrubicin (AMR) and cardiotoxicity in second-line treatment of small cell lung cancer (SCLC): A pooled analysis of left ventricular ejection fraction (LVEF) in two phase II trials

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19019-e19019
Author(s):  
D. R. Spigel ◽  
C. Shah ◽  
P. Lorigan ◽  
R. McNally ◽  
M. Renschler ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Pooled Analysis ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Line Treatment ◽  
Second Line ◽  
Phase Ii Trials ◽  
Two Phase ◽  
Ventricular Ejection Fraction ◽  
Study Results

e19019 Background: Amrubicin (AMR) is a third-generation synthetic anthracycline and a potent topoisomerase II inhibitor approved in Japan for the treatment of lung cancer. In Japanese pre and postmarking studies, AMR treatment was not associated with cardiotoxicity. The purpose of this analysis was to determine if AMR treatment of Western patients (pts) is associated with anthracycline-induced cardiomyopathy. Methods: To evaluate risk of cardiomyopathy, LVEF was measured by echocardiogram or by multiple gated acquisition (MUGA) scan and pooled from pts enrolled in 2 trials of IV AMR, 40 mg/m2/day x 3 days q 21 days for second-line treatment of sensitive or refractory SCLC. Pts with measurable disease, ECOG PS 0–2, LVEF ≥50%, and prior platinum-based treatment were assessed at baseline (BL), cycles 3, 6, then every 2 cycles, and end of treatment. Pts were to be assessed by the same method (ECHO or MUGA) throughout the study. Pts with a persistent ≥20% decrease in LVEF during treatment were to be removed from the study. Results: 112 patients were treated (sensitive n=43, median 6 cycles; refractory, n=69, median 5 cycles) and had at least 1 LVEF assessment. Median age was 63 years and median BL LVEF was 60%. Changes in LVEF from baseline were minimal ( Table ) and similar across cumulative dosing groups including 15 pts who received a cumulative dose of >1,000 mg/m2 AMR. Two refractory pts (1.8%) experienced drops in LVEF >20%. One had BL LVEF of 85%, then 60% at cycle 3, and 70% subsequently with ongoing therapy. The second, with a history of cardiomegaly, had LVEF of 55% at BL, cycle 3, and 5 by ECHO, and 29% at the time of progression after cycle 9 (cumulative AMR dose 840 mg/m2) by MUGA. The patient died due to progressive disease with no evidence of CHF. Conclusions: In this pooled analysis of SCLC pts, LVEF remained stable even in pts with cumulative AMR dosing >1,000 mg/m2. AMR for second-line treatment of SCLC does not appear to cause anthracycline-related cardiomyopathy. [Table: see text] [Table: see text]

Phase II study evaluating the association of gemcitabine, trastuzumab, and erlotinib as first-line treatment in patients with metastatic pancreatic adenocarcinoma (GATE 1).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 379-379 ◽  
Author(s):  
Eric Assenat ◽  
Laurent Mineur ◽  
Caroline Mollevi ◽  
Catherine Lombard-Bohas ◽  
Thibault Mazard ◽  
...  
Keyword(s):  
Performance Status ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Line Treatment ◽  
First Line ◽  
Open Label ◽  
Ventricular Ejection Fraction ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
First Line Treatment

379 Background: This study aimed to assess the efficacy and tolerance of the combinationof chemotherapy and two targeted therapies as a first-line treatment in metastatic pancreatic cancer patients. Methods: We designed a phase 2 open-label, non-comparative, multicenter study (NCT01204372). Patients received weekly 1000 mg/m² gemcitabine (3 weeks out of 4), weekly trastuzumab (4 mg/kg the first week, 2 mg/kg afterwards) and erlotinib 100 mg/day per os. The primary endpoint was the disease control rate (DCR) according to RECIST. Using a Fleming’s single-stage procedure, the trial was considered positive if 29 patients had a controlled disease (out of 57 evaluable patients). Secondary endpoints included the safety, the progression-free survival (PFS) and the overall survival (OS). An ancillary study addressed the EGFR, HER2 and KRAS status of the patients. Results: Between June 2010 and July 2013, 62 patients were recruited (37 men). The median age was 62 years (range 35-77). Performance status was 0 (n=27) and 1 (n=35). 10 patients had had a surgery of the primary tumor (PT), of whom 6 had been treated with a gemcitabine-based adjuvant chemotherapy (> 6-month delay). PT were localized in the head (n=25), corpus (n=22) and tail (n=15) of pancreas. The number of metastatic sites varied from 1 (n=25) to ≥ 3 (n=15). The baseline median left ventricular ejection fraction was 65% (range 51-86%). All patients were evaluable for safety and 59 patients for efficacy. Main first cycle treatment-related toxicities included: grade 3 anorexia (27%), asthenia (13%), diarrhea (10%), anemia (6%), and thrombocytopenia (3%); grade 3-4 neutropenia (24%), and mucositis (6%); grade 2-3 cutaneous events (35%). No complete responses were observed. 11 patients had a partial response, 33 a stable disease and 15 a disease progression. Therefore, the DCR was 74.6% (95%CI: 61.6-85.0%). Definitive results for the secondary endpoints will be presented at the meeting. Conclusions: Our results showed that combining gemcitabine, trastuzumab and erlotinib is efficient in terms of DCR. A further study is necessary to investigate this promising association. Funding (Roche SAS). Clinical trial information: NCT01204372.

scholarly journals Complications of X-ray Endovascular Interventions in Patients with Coronary Heart Disease with Reduced Left Ventricular Systolic Function

2021 ◽  
pp. 10-14
Author(s):  
Yevhenii V. Aksenov ◽  
Ruslan B. Demchenko
Keyword(s):  
Systolic Function ◽  
Mean Value ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Ventricular Ejection Fraction ◽  
X Ray ◽  
Coronary Syndrome ◽  
Coronary Stent Implantation ◽  
Study Results

The work is dedicated to the research of direct results and immediate possible complications of interventions in X-ray surgery with coronary stent implantation. Our patients with chronic coronary syndrome and reduced left ventricular ejection fraction (LVEF) of less than 40% were studied. The study included 112 patients who were divided into two groups. The first group included 51 patients with LVEF <40% (mean value 32.8 ± 1.14%), the second group involved 61 patients with LVEF >40% (mean value 59.4 ± 1.02%). The mean age of the subjects ranged from 59 to 74 years (mean value 63.85 ± 1.73 years). There were no gender-related differences among the selected patients. There was no statistical difference in comorbidities in both groups. Both groups of patients were examined and managed according to the protocol of diagnosis and treatment adopted at the National Amosov Institute of Cardiovascular Surgery for patients suffering from chronic coronary syndrome. The study results show that patients with coronary artery disease and reduced LVEF 2 times more often developed complications in early postoperative period after PCI with revascularization through stent placement than in group of patients with preserved contractile myocardial function. Duration of PCI procedure and contrast agent use was 26.3±1.4% and 29.8±4.2% higher, respectively; the frequency of life-threatening arrhythmias was 54% higher. Intraoperational signs of acute heart failure developed 4.8 times less often in the control group than in the experimental group. In general, all the patients after stenting achieved good anti-ischemic effect.

Multicenter, phase II study of trastuzumab and paclitaxel to treat HER2-positive, metastatic gastric cancer patients naive to trastuzumab (JFMC45-1102).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4096-4096 ◽  
Author(s):  
Satoru Iwasa ◽  
Kazuhiro Nishikawa ◽  
Akira Miki ◽  
Hirokazu Noshiro ◽  
Akira Tsuburaya ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Metastatic Gastric Cancer ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Line Treatment ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Multicenter Phase

4096 Background: The ToGA study indicated that first-line treatment using trastuzumab (T-mab) combined with capecitabine and cisplatin conferred a survival (OS) benefit to patients with HER2-positive metastatic gastric cancer (mGC). However, no reports have described the efficacy and safety of second-line treatment of HER2-positive mGC patients with T-mab who were naïve to the drug. Methods: JFMC45-1102 was a multicenter, Phase II study. Patients positive for HER2 (IHC3+ or IHC2+/FISH+) with gastric adenocarcinoma confirmed histologically; older than ≥ 20 y; who received one or more prior chemotherapies but no prior therapy with T-mab; and normal left ventricular ejection fraction (LVEF ≥ 50%) were eligible. Patients received paclitaxel (80 mg/m2on days 1, 8, and, 15 q4w) plus T-mab (8 mg/kg initial dose, followed by 6 mg/kg q3w). Treatment continued until their disease progressed; there was unacceptable toxicity or patient’s refused further treatment. The primary endpoint was overall response rate (ORR) evaluated according to RECIST ver. 1.0. Threshold and expected ORR were estimated at 15% and 30%, and secondary endpoints included progression free survival (PFS), time to treatment failure (TTF), overall survival (OS) and safety. Results: Fourty-six patients were enrolled between September 2011 and March 2012. Patients characteristics were: gender (M/F) 37/9; median age 69; ECOG PS0/1/2, 35/10/1; unresectable/recurrence 25/21; number of prior treatments (1/2), 41/5. The ORR was 37.2% (95% CI: 23.0-53.3%). The median PFS and TTF were 5.2 months (95% CI 3.9-6.6) and 5.2 months (95% CI 3.9-6.6), respectively. The protocol was discontinued for 27 patients (87.1%) for disease progression, and one patient each (3.2%) for severe adverse events, physician’s recommendation, patient refusal, and treatment related death. Conclusions: Combination chemotherapy of paclitaxel plus T-mab showed promising activity and was tolerated well by patients naïve to T-mab who were positive for HER2 and treated previously for mGC. Clinical trial information: UMIN000006223.

Docetaxel (Taxotere) shows survival and quality-of-life benefits in the second-line treatment of non[ndash ]small cell lung cancer: A review of two phase III trials

2001 ◽  
Vol 28 (1C) ◽  
pp. 4-9 ◽  
Author(s):  
Frances A. Shepherd ◽  
Frank V. Fossella ◽  
Thomas Lynch ◽  
Jean-Pierre Armand ◽  
James R. Rigas ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Lung Cancer ◽  
Small Cell ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Small Cell Lung ◽  
Two Phase ◽  
Phase Iii Trials

scholarly journals Current and Emerging Pharmacotherapies for the Treatment of Relapsed Small Cell Lung Cancer

2011 ◽  
Vol 5 ◽  
pp. CMO.S5964 ◽  
Author(s):  
Binu S. Nair ◽  
Vipul Bhanderi ◽  
Syed H. Jafri
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Single Agent ◽  
Small Cell ◽  
Line Treatment ◽  
Second Line ◽  
Small Cell Lung ◽  
Phase Ii Trials ◽  
Aggressive Cancer

Small cell lung cancer (SCLC) is a very aggressive cancer with poor outcome if left untreated, but it is also one of the most chemotherapy responsive cancers. Overall it has a very poor prognosis especially if it is chemotherapy resistant to first line treatment. Second line chemotherapy has not been very beneficial in SCLC as opposed to breast cancer and lymphoma. In the last few years topotecan is the only drug that has been approved by the food and drug administration (FDA) for the second line treatment of SCLC but in Japan another drug, amrubicin is approved. There are many combinations of different chemotherapies available in moderate to high intensity, in this difficult to treat patient to overcome the chemo resistance, but many of these studies are small or phase II trials. In this article we have reviewed single agent and multidrug regimens that were studied in both chemo sensitive and refractory setting, including the most recent clinical trials.

scholarly journals The Role of Anti-Angiogenics in Pre-Treated Metastatic BRAF-Mutant Colorectal Cancer: A Pooled Analysis

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1022 ◽  
Author(s):  
Fabio Gelsomino ◽  
Andrea Casadei-Gardini ◽  
Daniele Rossini ◽  
Alessandra Boccaccino ◽  
Gianluca Masi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Two Phase ◽  
Randomized Controlled Studies ◽  
Mutational Status ◽  
The Impact ◽  
Braf Mutant

Background. FOLFOXIRI plus Bevacizumab is one of the most frequently used first-line treatments for patients with BRAF-mutant colorectal cancer (CRC), while second-line treatment requires extensive further research. In this pooled analysis, we evaluate the impact of anti-angiogenics in patients with pre-treated BRAF-mutant CRC. Methods. We monitored patients in randomized, controlled studies who had advanced CRC and were undergoing second-line chemotherapy in addition to utilizing Bevacizumab, Ramucirumab or Aflibercept treatments. These data were pooled together with the data and results of BRAF-mutant patients enrolled in two phase III trials (TRIBE and TRIBE-2 study), who had been treated with second-line treatment both with or without Bevacizumab. Overall survival (OS), in relation to BRAF mutational status, was the primary focus. Results. Pooled analysis included 129 patients. Anti-angiogenics were found to have a significant advantage over the placebo in terms of OS (HR 0.50, 95%CI 0.29–0.85) (p = 0.01). Conclusions. Our pooled analysis confirms the efficacy of anti-angiogenics in pre-treated BRAF-mutant CRC, establishing the combination of chemotherapy plus Bevacizumab or Ramucirumab or Aflibercept as a valid treatment option.

Sign in / Sign up

Export Citation Format

Share Document