Initial results of a phase III study show safety of HRT and low dose tamoxifen

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1009-1009
Author(s):  
B. Bonanni ◽  
B. Santillo ◽  
D. Serrano ◽  
U. Veronesi ◽  
M. Rosselli Del Turco ◽  
...  
Keyword(s):  
De Novo ◽  
Standard Dose ◽  
Hot Flashes ◽  
Population Characteristics ◽  
Phase Iii ◽  
Antiproliferative Effects ◽  
Phase Iii Study ◽  
Anxiety Depression

1009 Background: HRT is beneficial on menopausal disturbancies and decreased bone fracture risk and colorectal cancer (CRC), but increased VTE, cardiovascular events and breast cancer in the WHI trial. However, the WHI characteristics (median age 63.3 yrs, median BMI 28.5, use of oral HRT) diminish generalization of results. The WHI trial shows an increased BC risk, only with oral combined HRT. HRT and tamoxifen (T) was safe in subgroups of two prevention trials. T at low doses showed antiproliferative effects similar to the standard dose, without significant menopausal symptoms and endometrial proliferation. Methods: The HRT+T combination is being investigated in a multicentric, phase III trial in current or de novo HRT users, randomized to either T 5 mg/day or placebo for 5 yrs. The primary endpoint is the reduction of invasive and in situ BC. Results: Of 5,032 women contacted, 1,989 refused, 1,109 were not eligible, and 1,806 were enrolled in 46 centres. Median age is 53 years (33–72). BMI is <20 in 65.7%, <25 in 26.3%, >25 in 8.0%. Current or de novo users are 80.1% and 19.9%. In the former group, 45.9% use oral and 54.1% use TTS. Hysterectomized women are 389. Current users ≤3 years are 48.0%, 3–5 years 12.1%, >5 years 18.8%. 1256 women (74.2%) have at least one follow-up visit. Compared to baseline, most frequent side effects were: hot flashes (42.0% vs 35.0%), night sweating (39.0% vs 29.0%), anxiety/depression (41.0% vs 27.4%), vaginal dryness (29.2% vs 19.3%), headache (32.1% vs 25.1%), fluid retention (24.0% vs 19.0%). “Drop-outs” are 17.3%, of which 11.2% due to adverse events (AE). The 35 AE include: 12 cancers (incl. 7 invasive BC’s, 1 DCIS, 1 CRC), 11 cardiovascular (incl. 1 stroke, 1 AMI, 2 VTE, 1 angina, 2 TIA), 2 gynecologic (uterine polyps). Conclusions: In spite of the current negative scenario for HRT, we have reached over 1,800 women on study. Compliance is acceptable and treatment appears safe. The rate of AE is far lower than the WHI trial, possibly as a result of the different population characteristics. These preliminary findings justify the carry-on of the study in order to reach enough power for the main endpoint and perform secondary evaluations. No significant financial relationships to disclose.

scholarly journals Associations between Amplification (1q) and Prior Cancer in a Real-World De Novo Myeloma Cohort

2021 ◽  
Author(s):  
Elizabeth B Lamont ◽  
Andrew J Yee ◽  
Stuart L Goldberg ◽  
David S Siegel ◽  
Andrew D Norden
Keyword(s):  
Real World ◽  
Fluorescent In Situ Hybridization ◽  
De Novo ◽  
Chromosome 1 ◽  
Second Malignancies ◽  
Cancer History ◽  
Screening Strategies ◽  
Cytogenetic Testing

Abstract Genomic biomarkers inform treatment in multiple myeloma (MM) making patient clinical data a potential window into MM biology. We evaluated de novo MM patients for associations between specific MM cytogenetic patterns and prior cancer history. Analyzing a MM real-world dataset (RWD), we identified a cohort of 1,769 patients with fluorescent in-situ hybridization (FISH) cytogenetic testing at diagnosis. Fully 241 patients (0.14) had histories of prior cancer(s). Amplification of the long arm of chromosome 1 [amp(1q)] varied by prior cancer history (0.31 with prior cancer vs 0.24 without; p = .02). No other MM translocations, amplifications, or deletions were associated with prior cancers. Amp(1q) and cancer history remained strongly associated in a logistic regression adjusting for patient demographic and disease attributes. The results merit follow-up regarding carcinogenic treatment effects and screening strategies for second malignancies. Broadly the findings suggest analyses of patient-level phenotypic-genomic RWD may accelerate cancer research through hypothesis generating studies.

scholarly journals Tacrolimus Once Daily (ADVAGRAF) Versus Twice Daily (PROGRAF) in De Novo Renal Transplantation: A Randomized Phase III Study

2010 ◽  
Vol 10 (12) ◽  
pp. 2632-2643 ◽  
Author(s):  
B. K. Krämer ◽  
B. Charpentier ◽  
L. Bäckman ◽  
H. Tedesco Silva Jr ◽  
G. Mondragon-Ramirez ◽  
...  
Keyword(s):  
Renal Transplantation ◽  
De Novo ◽  
Phase Iii ◽  
Once Daily ◽  
Phase Iii Study

Breast-Conserving Treatment With or Without Radiotherapy in Ductal Carcinoma-In-Situ: Ten-Year Results of European Organisation for Research and Treatment of Cancer Randomized Phase III Trial 10853—A Study by the EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group

2006 ◽  
Vol 24 (21) ◽  
pp. 3381-3387 ◽  
Author(s):  
Nina Bijker ◽  
Philip Meijnen ◽  
Johannes L. Peterse ◽  
Jan Bogaerts ◽  
Irène Van Hoorebeeck ◽  
...  
Keyword(s):  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Phase Iii ◽  
Breast Conserving Treatment ◽  
European Organisation ◽  
Radiotherapy Group ◽  
Long Term Follow Up

Purpose The European Organisation for Research and Treatment of Cancer conducted a randomized trial investigating the role of radiotherapy (RT) after local excision (LE) of ductal carcinoma-in-situ (DCIS) of the breast. We analyzed the efficacy of RT with 10 years follow-up on both the overall risk of local recurrence (LR) and related to clinical, histologic, and treatment factors. Patients and Methods After complete LE, women with DCIS were randomly assigned to no further treatment or RT (50 Gy). One thousand ten women with mostly (71%) mammographically detected DCIS were included. The median follow-up was 10.5 years. Results The 10-year LR-free rate was 74% in the group treated with LE alone compared with 85% in the women treated by LE plus RT (log-rank P < .0001; hazard ratio [HR] = 0.53). The risk of DCIS and invasive LR was reduced by 48% (P = .0011) and 42% (P = .0065) respectively. Both groups had similar low risks of metastases and death. At multivariate analysis, factors significantly associated with an increased LR risk were young age (≤ 40 years; HR = 1.89), symptomatic detection (HR = 1.55), intermediately or poorly differentiated DCIS (as opposed to well-differentiated DCIS; HR = 1.85 and HR = 1.61 respectively), cribriform or solid growth pattern (as opposed to clinging/micropapillary subtypes; HR = 2.39 and HR = 2.25 respectively), doubtful margins (HR = 1.84), and treatment by LE alone (HR = 1.82). The effect of RT was homogeneous across all assessed risk factors. Conclusion With long-term follow-up, RT after LE for DCIS continued to reduce the risk of LR, with a 47% reduction at 10 years. All patient subgroups benefited from RT.

scholarly journals Final Results of the IELSG-19 Randomized Trial of Mucosa-Associated Lymphoid Tissue Lymphoma: Improved Event-Free and Progression-Free Survival With Rituximab Plus Chlorambucil Versus Either Chlorambucil or Rituximab Monotherapy

2017 ◽  
Vol 35 (17) ◽  
pp. 1905-1912 ◽  
Author(s):  
Emanuele Zucca ◽  
Annarita Conconi ◽  
Giovanni Martinelli ◽  
Reda Bouabdallah ◽  
Alessandra Tucci ◽  
...  
Keyword(s):  
Overall Survival ◽  
Randomized Trial ◽  
Lymphoid Tissue ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
Final Sample ◽  
Phase Iii Study ◽  
To Receive

Purpose There is no consensus on the optimal systemic treatment of patients with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The IELSG-19 phase III study, to our knowledge, was the first such study to address the question of first-line treatment in a randomized trial. Patients and Methods Eligible patients were initially randomly assigned (1:1 ratio) to receive either chlorambucil monotherapy (6 mg/m2/d orally on weeks 1 to 6, 9 to 10, 13 to 14, 17 to 18, and 21 to 22) or a combination of chlorambucil (same schedule as above) and rituximab (375 mg/m2 intravenously on day 1 of weeks 1, 2, 3, 4, 9, 13, 17, and 21). After the planned enrollment of 252 patients, the protocol was amended to continue with a three-arm design (1:1:6 ratio), with a new arm that included rituximab alone (same schedule as the combination arm) and with a final sample size of 454 patients. The main end point was event-free survival (EFS). Analysis of chlorambucil versus the combination arm was performed and reported separately before any analysis of the third arm. Results At a median follow-up of 7.4 years, addition of rituximab to chlorambucil led to significantly better EFS (hazard ratio, 0.54; 95% CI, 0.38 to 0.77). EFS at 5 years was 51% (95% CI, 42 to 60) with chlorambucil alone, 50% (95% CI, 42 to 59) with rituximab alone, and 68% (95% CI, 60 to 76) with the combination ( P = .0009). Progression-free survival was also significantly better with the combination ( P = .0119). Five-year overall survival was approximately 90% in each arm. All treatments were well tolerated. No unexpected toxicities were recorded. Conclusion Rituximab in combination with chlorambucil demonstrated superior efficacy in mucosa-associated lymphoid tissue lymphoma; however, improvements in EFS and progression-free survival did not translate into longer overall survival.

The onset of dementia in patients with an acute ischemic stroke

2011 ◽  
Vol 26 (S2) ◽  
pp. 484-484
Author(s):  
C. Bacila
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Cognitive Deficits ◽  
De Novo ◽  
Cognitive Disorder ◽  
Number Of Patients ◽  
Great Prevalence ◽  
Dsm Iv ◽  
Anxiety Depression

IntroductionStroke is a disorder that has great prevalence, defined vascular territories and psychiatric signs generally emerge in association with specific cognitive deficits.ObjectiveDementia occurs frecquently after acute ischemic stroke. The incidence of dementia six months after stroke is about 42%. Fortunately, in recent years, more attention has been paid to organic disorders provoked by strokes, especially to dementia.AimTo follow up the occuring dementia after stroke and also to follow the various psychiatric disorders with the onset during or after an acute ischemic stroke.MethodsAltogether 110 patients were recruited to this observational and non-interventional study, patients who were suffering from a psychiatric disorder after an ischemic stroke (according to DSM IV TR). The screening was followed by four visits during six months, when CGI, 17-HAMD, CROCQ and MMSE scales were used.ResultsOf 110 patients, 39,09% has been diagnosed with dementia. A number of these patients (n = 26) developed an onset like paroxistic disorder (60,46%), or an acute syndrom (20,93%) and 8 patients were considered “de novo” (with the onset of cognitive impairement after 60 days). There were various acute disorders occuring in the onset of dementia, that includes: amnestic syndrom, organic delirium, organic anxiety syndrom and a small number of patients (n=2) who developed mild cognitive disorder.ConclusionsThe literature considers vascular dementia occuring after an ischemic stroke and increasing step by step mnestic deficits; our study releaved a metamorphosis of various types of onset (anxiety, depression, delirium) or cognitive impairement could occurs after 30 days.

Outcomes in CCG-2961, a Children’s Cancer Group Phase III Trial for Untreated Acute Myeloid Leukemia (AML).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 169-169 ◽  
Author(s):  
Beverly J. Lange ◽  
Franklin O. Smith ◽  
Patricia A. Dinndorf ◽  
Carola A.S. Arndt ◽  
Dorothy R. Barnard ◽  
...  
Keyword(s):  
De Novo ◽  
Interleukin 2 ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Remission Induction ◽  
High Dose ◽  
Free Survival ◽  
Cancer Group ◽  
De Novo Aml

Abstract CCG-2961 tested an intensively timed induction therapy consisting of cytarabine (AC), etoposide, thioguanine, dexamethasone, idarubicin and daunorubicin. Patients in remission after induction were randomized to a second induction course (Arm A) or a 3-drug combination of fludarabine, AC, and idarubicin (Arm B). Course 3 for patients with related donors was bone marrow transplantation (BMT); for those without donors, high dose AC/l-asparaginase. After Course 3 patients without donors were randomized to 14 infusions of Interleukin 2 (IL2) over 18 days or follow-up. CNS prophylaxis was intrathecal AC. Eligibility included all subtypes of de novo AML except acute promyelocytic leukemia and AML in patients with Down syndrome. CCG-2961 opened in Oct.1996 and closed in Dec. 2002. The DSMC suspended the study between Oct. 1999 and May 2000 while the 2961 Committee developed supportive care policies to reduce treatment-related mortality (TRM). CCG-2961 enrolled 900 de novo patients aged 3 days to 21 years, with 495 and 405 patients accruing pre-and post suspension respectively. Remission induction rate is 88.5%. With median follow-up of 3.6 years (range: 0 – 8.1 years), event-free survival (EFS) at 3 years is 44±3% and survival (OS) 57±3%. Disease-free survival (DFS) following Course 2 Arms A and B are not different, although relapse is significantly higher in Arm A (7.3% .vs. 3.1% P=0.018) and TRM more common in Arm B (7.9% vs.4.2% P=0.059), despite 7 less days of neutropenia in Arm B (P&lt;0.001). DFS is 65±9% for patients with a donor versus 50±5% for patients without a donor (P=0.005); respective OS, 74±8% and 66±5% (P=0.221). However, among 98 patients in CR1 with t(8;21) or inv(16) cytogenetics, outcomes in those without and with a donor were no different: DFS (61±12% vs. 72±18%, P = 0.49) and OS (78±10% vs. 77±17%, l P= 0.85). DFS with and without IL2 is 55±9% and 60±8%(P=0.606). Outcomes improved progressively over time. EFS pre- and post-suspension are 41±4% and 47±5%(P=0.038); OS, 52±5% and 63±5%(P=0.005); TRM is 17±3% pre- and 12±3% post-suspension (P=0.039). Factors predictive of inferior EFS are age &gt;17 years, Afro-American and Hispanic ethnicity, body mass index &lt;10th or &gt;95th percentile for age, absence of related marrow donor, WBC &gt; 50,000/mm3, karyotype with −7/7q, −5/5q- or &gt; cytogenetic 5 abnormalities, FLT3/ITD, &gt;15 % morphologic blasts on day 14 or &gt;0.5% immunologically detectable blasts at the end of induction. CCG-2961 confirms the efficacy and high TRM of intensively timed therapy. Neither fludarabine nor IL2 increases DFS or OS, and availability of a donor does not improve outcomes in those with favorable cytogenetics.

A Double Blind Placebo-Controlled Randomized Phase III Study of High Dose Continuous Infusion Cytosine Arabinoside (araC) with or without Cloretazine® in Patients with First Relapse of Acute Myeloid Leukemia (AML).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1970-1970
Author(s):  
Francis J. Giles ◽  
Wendy Stock ◽  
Norbert Vey ◽  
Karen Seiter ◽  
Daniel J. DeAngelo ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
De Novo ◽  
Early Death ◽  
Hematologic Malignancies ◽  
Data Safety Monitoring Board ◽  
Phase Iii ◽  
High Dose ◽  
Double Blind ◽  
Phase Iii Study ◽  
First Relapse

Abstract Background: AraC is considered to be the most effective single drug in the treatment of AML. For initial treatment of AML, araC is typically administered by intravenous continuous infusion for 5–7 days at doses of 100–200 mg/m2/day, usually in combination with an anthracycline. In the relapsed setting, araC remains an option for treatment and is generally administered at higher doses either alone or in combination with other agents and in a variety of schedules. Cloretazine (VNP40101M) is a novel alkylating agent that preferentially targets the O6 position of guanine. A Phase I trial of Cloretazine with araC in advanced hematologic malignancies demonstrated significant anti-leukemic activity with minimal extramedullary toxicity (Giles et al, 2005). The purpose of the current double blind randomized Phase III study is to determine if araC with Cloretazine improves outcome in AML patients (pts) in first relapse. Methods: Eligible pts must be ≥18 years old, PS 0–2, and have AML in first relapse following a CR or CRp of 3–24 months duration. Pts are randomized using a 2:1 scheme to receive either araC 1.5 gm/m2 (d 1–3) + Cloretazine 600mg/m2 or placebo on d 2. Pts are stratified by both age and remission duration. Pts achieving CR or CRp are consolidated with araC + Cloretazine 400mg/m2, or araC + placebo according to original treatment assignment. Pts with partial response or bone marrow improvement may receive a second induction cycle. The study will accrue 420 pts, with an interim analysis for safety and efficacy at 210 pts. The primary endpoint is overall response (CR and CRp) rate. Secondary endpoints include time-to-progression, duration of response, and survival. Results: A data safety monitoring board review of the first 32 pts was performed in 12/05. Differential toxicity between the two arms was not observed. From 03/05 to 07/06, 164 pts were enrolled by 47 sites. Median age=59 yrs (range 22–83), and 52%= male. Distribution by stratum: I = 66 (<60, CR<12mos); II= 22 (<60, CR≥12mos); III= 45 (≥60, CR<12mos); IV= 31 (≥60, CR≥12mos). Blinded data are available for 110 monitored pts: 77% were de novo AML, 23% secondary AML. 107/110 pts completed the intended treatment course. The most common reported serious adverse event was infection (50%). Importantly, of 110 pts, early deaths (≤30 days from start of treatment) occurred in only 13 (12%) pts, most of which was due to infection with neutropenia, or progressive disease. Conclusions: A multi-site Phase III double-blind randomized trial for pts with AML in first relapse is feasible and demonstrates a recognized clinical need for new treatments across age and CR duration variables. The ability of pts to tolerate high-dose araC with or without Cloretazine as assessed by rate of SAE and early death is encouraging.

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