Bortezomib(Velcade®)-Thalidomide-Dexamethasone (VTD) Is Superior to Thalidomide-Dexamethasone (TD) In Patients with Multiple Myeloma (MM) Progressing or Relapsing After Autologous Transplantation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3043-3043
Author(s):  
Laurent Garderet ◽  
Simona Iacobelli ◽  
Philippe Moreau ◽  
Mamoun Dib ◽  
Denis Caillot ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Cox Model ◽  
Autologous Transplantation ◽  
Rest Period ◽  
Phase Iii ◽  
Rank Test ◽  
Primary Study ◽  
Log Rank Test ◽  
One Year ◽  
To Receive

Abstract Abstract 3043 Introduction: The Thalidomide-Dexamethasone (TD) regimen has provided encouraging results in relapsed MM. To improve results, bortezomib (Velcade) has been added to the combination in previous phase II studies, the so called VTD regimen. In January 2006, the European Group for Blood and Marrow Transplantation (EBMT) and the Intergroupe Francophone du Myélome (IFM) initiated a prospective, randomized, parallel-group, open-label phase III, multicenter study, comparing VTD (arm A) with TD (arm B) for MM patients progressing or relapsing after autologous transplantation. Patients and Methods: Inclusion criteria: patients in first progression or relapse after at least one autologous transplantation, including those who had received bortezomib or thalidomide before transplant. Exclusion criteria: subjects with neuropathy above grade 1 or non secretory MM. Primary study end point was time to progression (TTP). Secondary end points included safety, response rate, progression-free survival (PFS) and overall survival (OS). Treatment was scheduled as follows: bortezomib 1.3 mg/m2 was given as an i.v bolus on Days 1, 4, 8 and 11 followed by a 10-Day rest period (days 12 to 21) for 8 cycles (6 months) and then on Days 1, 8, 15, 22 followed by a 20-Day rest period (days 23 to 42) for 4 cycles (6 months). In both arms, thalidomide was scheduled at 200 mg/Day orally for one year and dexamethasone 40 mg/Day orally four days every three weeks for one year. Patients reaching remission could proceed to a new stem cell harvest. However, transplantation, either autologous or allogeneic, could only be performed in patients who completed the planned one year treatment period. Response was assessed by EBMT criteria, with additional category of near complete remission (nCR). Adverse events were graded by the NCI-CTCAE, Version 3.0.The trial was based on a group sequential design, with 4 planned interim analyses and one final analysis that allowed stopping for efficacy as well as futility. The overall alpha and power were set equal to 0.025 and 0.90 respectively. The test for decision making was based on the comparison in terms of the ratio of the cause-specific hazards of relapse/progression, estimated in a Cox model stratified on the number of previous autologous transplantations. Relapse/progression cumulative incidence was estimated using the proper nonparametric estimator, the comparison was done by the Gray test. PFS and OS probabilities were estimated by the Kaplan-Meier curves, the comparison was performed by the Log-Rank test. An interim safety analysis was performed when the first hundred patients had been included. The safety committee recommended to continue the trial. Results: As of 1st July 2010, 269 patients had been enrolled in the study, 139 in France (IFM 2005-04 study), 21 in Italy, 38 in Germany, 19 in Switzerland (a SAKK study), 23 in Belgium, 8 in Austria, 8 in the Czech republic, 11 in Hungary, 1 in the UK and 1 in Israel. One hundred and sixty nine patients were males and 100 females; the median age was 61 yrs (range 29–76). One hundred and thirty six patients were randomized to receive VTD and 133 to receive TD. The current analysis is based on 246 patients (124 in arm A, 122 in arm B) included in the second interim analysis, carried out when 134 events were observed. Following this analysis, the trial was stopped because of significant superiority of VTD over TD. The remaining patients were too premature to contribute to the analysis. The number of previous autologous transplants was one in 63 vs 60 and two or more in 61 vs 62 patients in arm A vs B respectively. The median follow-up was 25 months. The median TTP was 20 months vs 15 months respectively in arm A and B, with cumulative incidence of relapse/progression at 2 years equal to 52% (95% CI: 42%-64%) vs 70% (95% CI: 61%-81%) (p=0.0004, Gray test). The same superiority of arm A was also observed when stratifying on the number of previous autologous transplantations. At 2 years, PFS was 39% (95% CI: 30%-51%) vs 23% (95% CI: 16%-34%) (A vs B, p=0.0006, Log-Rank test). OS in the first two years was comparable in the two groups. Conclusion: VTD resulted in significantly longer TTP and PFS in patients relapsing after ASCT. Analysis of response and safety data are on going and results will be presented at the meeting. Protocol EU-DRACT number: 2005-001628-35. Disclosures: Niederwieser: Bristol-Myers Squibb: Speakers Bureau; Novartis: Speakers Bureau.

An EORTC Gastrointestinal Group phase III evaluation of combinations of methyl-CCNU, 5-fluorouracil, and adriamycin in advanced gastric cancer.

1987 ◽  
Vol 5 (9) ◽  
pp. 1387-1393 ◽  
Author(s):  
A Lacave ◽  
J Wils ◽  
H Bleiberg ◽  
E Diaz-Rubio ◽  
N Duez ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Response Rate ◽  
Multicenter Trial ◽  
Phase Iii ◽  
Rank Test ◽  
Short Survival ◽  
Log Rank Test ◽  
Prospective Phase ◽  
To Receive

In a prospective phase III multicenter trial, 189 patients with advanced measurable and nonmeasurable gastric cancer were randomized to receive 5-fluorouracil (5-FU) combined with Adriamycin (FA) or FA plus methyl-CCNU (MeFA). The response rate in patients with measurable disease was 10% (three of 29), and 18% (five of 28), respectively. No difference in the duration of survival was detected (P = .14; log rank test). Median survivals were 21 and 32 weeks, respectively. Toxicity was moderate, but there have been two toxic deaths among the patients who received FA. Because of the low response rate and the short survival, neither regimen can be recommended for the treatment of advanced gastric cancer.

Bortezomib (Velcade®)-Thalidomide-Dexamethasone (VTD) vs Thalidomide-Dexamethasone (TD) in Preparation for Autologous Stem-Cell (SC) Transplantation (ASCT) in Newly Diagnosed Multiple Myeloma (MM).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 73-73 ◽  
Author(s):  
Michele Cavo ◽  
Francesca Patriarca ◽  
Paola Tacchetti ◽  
Monica Galli ◽  
Giulia Perrone ◽  
...  
Keyword(s):  
Partial Response ◽  
Induction Therapy ◽  
Autologous Transplantation ◽  
Phase Iii ◽  
Primary Study ◽  
Control Group ◽  
Induction Phase ◽  
Newly Diagnosed ◽  
Grade 3 ◽  
To Receive

Abstract In May 2006, the Italian Myeloma Network GIMEMA initiated a multicenter, randomized phase III study comparing VTD (arm A) with TD (arm B) incorporated into ASCT for newly diagnosed MM. Both VTD and TD were planned to be administered before (induction) and after (consolidation) double ASCT with melphalan 200 mg/m2 (MEL-200). In both arms, induction therapy consisted of three 21-d courses [63 days (d)]. The VTD regimen included Vel, 1.3 mg/m2 on d 1, 4, 8, and 11, plus Dex, 40 mg on each day of and after Vel administration; Thal was given at 200 mg/d from d 1 to 63. Patients randomized to TD received Thal as in arm A and Dex 40 mg/d on d 1–4 and 9–12 of every 21-d cycle. Primary study end point was complete response [either immunofixation negative (CR) or immunofixation positive (nCR)] to induction therapy. Secondary study end points included CR+nCR to consolidation therapy, time to progression, event-free survival, overall survival and toxicity. An interim analysis was planned to be performed after one year from study initiation to assess efficacy and toxicity of induction therapy. As of May 30, 2007, 234 patients entered the study and 187 were evaluated for response to induction therapy and adverse events (AEs). Of these patients, 92 were randomly assigned to receive VTD and 95 to receive TD. Efficacy and toxicity analyses were performed on an intention-to-treat basis. The rate of CR+nCR to VTD was 38% vs 7% to TD (P<0.001); 60% of patients in VTD arm and 25% of patients in the control group attained at least a very good partial response (P<0.001). Patients who failed at least a partial response to VTD were significantly less than those who failed on TD (7% vs 21%, respectively; P=0.004). Grade ≥ 2 and grade ≥ 3 AEs were similar in both arms, with the exception of grade ≥ 3 skin rash (6.5% in VTD arm vs 1% in TD arm; P=0.04). Grade 3 peripheral neuropathy was reported in 8% of patients randomly assigned to VTD and in 2% of patients treated with TD (P=0.07). All patients received acyclovir prophylaxis against reactivation of varicella zoster virus (VZV). VZV infection occurred in 2% of patients in VTD arm and in 1% of patients in the control group. Treatment discontinuation due to AEs was required in a single patient in each of the two treatment arms. No patient died for any cause during the induction phase. In a subgroup of patients with longer follow-up response to first ASCT was also evaluated. The rate of CR or CR+nCR to MEL-200 was significantly higher in VTD arm than in the control group (P=0.02 for CR comparison and P=0.05 for CR+nCR comparison between the two treatment arms). Preliminary analysis of this study provides demonstration that VTD is a highly active and well tolerated induction regimen, resulting in a significantly higher CR or CR+nCR rate compared to TD both before ASCT and after the first autologous transplantation with MEL-200.

A randomized phase II study evaluating the activity of bevacizumab in combination with carboplatin plus paclitaxel in patients with previously untreated advanced mucosal melanoma (NCT02023710).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9521-9521
Author(s):  
Xieqiao Yan ◽  
Xinan Sheng ◽  
Lu Si ◽  
Zhihong Chi ◽  
Chuanliang Cui ◽  
...  
Keyword(s):  
Disease Control ◽  
Phase Ii ◽  
Cox Model ◽  
Mucosal Melanoma ◽  
Phase Iii ◽  
Study Endpoint ◽  
Primary Study ◽  
Open Label ◽  
Randomized Phase Ii ◽  
To Receive

9521 Background: Mucosal melanoma is rare and associated with extremely poor prognosis. There was no standard treatment for advanced mucosal melanoma patients. BEAM study had demonstrated the effectivity and safety of bevacizumab combined with carboplatin plus paclitaxel in patients with previously untreated metastatic melanoma. This study was to evaluate the activity of bevacizumab combined with carboplatin plus paclitaxel in Patients with Previously Untreated Advanced Mucosal Melanoma. Methods: This study is an open-label, multicenter, randomized phase II trial. Eligible patients had metastatic, recurrent, or unresectable mucosal melanoma and no received any systemic therapy before enrollment. Patients were randomly allocated in a 2:1 ratio to receive bevacizumab (CPB arm, 5mg/kg every two weeks) or placebo (CP arm) with carboplatin (area under the curve, 5) plus paclitaxel (175 mg/m2). Treatment was continued for both groups until disease progression, unacceptable toxicity, death, or withdrawal of consent. The primary study endpoint is progress-free survival (PFS). Overall survival, disease control rate, and safety will also be assessed. Results: The first patient visit was December 1st, 2013, and the final data cutoff was August 30th, 2018. At that time, 114 patients were randomly assigned to receive CP or CPB therapy. Median PFS was 3.2 months for the CP arm and 4.7 months for the CPB arm (HR, 0.50; 95% CI, 0.33-0.72; P = 0.001). Median OS was 9.0 months in the CP arm versus 12.9 months in the CPB arm (HR, 0.61; 95% CI, 0.40-0.92; P = 0.02). The PFS was longer in the CPB arm in the subgroups of patients with neutrophil-to-lymphocyte ratio (NLR) more than 4 and patients with abnormal lactate dehydrogenase concentration (1.2 v 3.0 months, HR, 0.38; 2.0 v 4.7 months, HR, 0.39, respectively). Multivariate analysis using the Cox model showed that combination with bevacizumab was the predictor for better disease control and survival (PFS: HR 0.400, 95% CI 0.251-0.636, P < 0.001; OS: HR 0.505, 95% CI 0.313-0.814, P = 0.005). No new safety signals were observed. Conclusions: To our knowledge this is the largest study about advanced mucosal melanoma. This study demonstrated that bevacizumab in combination with carboplatin plus paclitaxel is active and safe regimen as first line treatment in patients with in advanced mucosal melanoma. A phase III study will be necessary to confirm the benefit, especially in some special setting such as elevated NLR and elevated LDH subgroups. Clinical trial information: NCT02023710.

Randomized, Placebo-Controlled, Phase III Trial of Sunitinib Plus Prednisone Versus Prednisone Alone in Progressive, Metastatic, Castration-Resistant Prostate Cancer

2014 ◽  
Vol 32 (2) ◽  
pp. 76-82 ◽  
Author(s):  
M. Dror Michaelson ◽  
Stephane Oudard ◽  
Yen-Chuan Ou ◽  
Lisa Sengeløv ◽  
Fred Saad ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antiangiogenic Therapy ◽  
Oral Prednisone ◽  
Phase Iii ◽  
Rank Test ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Log Rank Test ◽  
Grade 3 ◽  
To Receive

Purpose We evaluated angiogenesis-targeted sunitinib therapy in a randomized, double-blind trial of metastatic castration-resistant prostate cancer (mCRPC). Patients and Methods Men with progressive mCRPC after docetaxel-based chemotherapy were randomly assigned 2:1 to receive sunitinib 37.5 mg/d continuously or placebo. Patients also received oral prednisone 5 mg twice daily. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS). Two interim analyses were planned. Results Overall, 873 patients were randomly assigned to receive sunitinib (n = 584) or placebo (n = 289). The independent data monitoring committee stopped the study for futility after the second interim analysis. After a median overall follow-up of 8.7 months, median OS was 13.1 months and 11.8 months for sunitinib and placebo, respectively (hazard ratio [HR], 0.914; 95% CI, 0.762 to 1.097; stratified log-rank test, P = .168). PFS was significantly improved in the sunitinib arm (median 5.6 v 4.1 months; HR, 0.725; 95% CI, 0.591 to 0.890; stratified log-rank test, P < .001). Toxicity and rates of discontinuations because of adverse events (AEs; 27% v 7%) were greater with sunitinib than placebo. The most common treatment-related grade 3/4 AEs were fatigue (9% v 1%), asthenia (8% v 2%), and hand–foot syndrome (7% v 0%). Frequent treatment-emergent grade 3/4 hematologic abnormalities were lymphopenia (20% v 11%), anemia (9% v 8%), and neutropenia (6% v < 1%). Conclusion The addition of sunitinib to prednisone did not improve OS compared with placebo in docetaxel-refractory mCRPC. The role of antiangiogenic therapy in mCRPC remains investigational.

Benefit from letrozole as extended adjuvant therapy after sequential endocrine therapy: A randomized, phase III study of Gruppo Italiano Mammella (GIM).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 504-504 ◽  
Author(s):  
Lucia Del Mastro ◽  
Mauro Mansutti ◽  
Giancarlo Bisagni ◽  
Riccardo Ponzone ◽  
Antonio Durando ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adjuvant Therapy ◽  
Endocrine Therapy ◽  
Cox Model ◽  
Disease Free Survival ◽  
Nodal Status ◽  
Phase Iii ◽  
Primary Study ◽  
Fisher Exact Test ◽  
To Receive

504 Background: The effect of extended adjuvant endocrine therapy (ET) with aromatase inhibitors (AI) after sequential ET with tamoxifen (Tam) followed by AI for 5 years is still controversial. We conduct a clinical trial to assess different durations of ET of letrozole after tam. Methods: The GIM4 LEAD (Gruppo Italiano Mammella 4- Letrozole adjuvant therapy duration study, ClinicalTrials.gov:NCT01064635 ) was a prospective, randomized, Italian multicentric trial. Post-menopausal patients (pts) with hormone receptor positive early breast cancer free of recurrence after 2-3 years of adjuvant tam, were randomized in a 1:1 ratio to receive 3-2 years (short arm, S) or 5 years (long arm, L) of letrozole. The primary study end point was disease-free survival (DFS). Results: Between August 2005 and May 2010, 2056 pts were randomly assigned to receive 3-2 years (n=1030) or 5 years (n=1026) of letrozole. Main patients characteristics in the S and L arms were, respectively: median age 60 vs 61 years, node negative 56 vs 56%, (neo)adjuvant chemotherapy 53.4 vs 54.1%. The median follow-up was 10 years (IQR range: 8.6-11.4). The 8-year DFS was 80% (95% CI:77.3-82.7) and 85% (95% CI:82.9-87.6) in the S and L arm, respectively (hazard ratio, HR 0.82; 95% CI:0.68-0.98; p=0.031). This effect did not change in a multivariate Cox model that included nodal status, grading and age. No evidence of interaction between random assignment and nodal status, age and grading was observed. Among 1960 pts evaluable for toxicity, osteoporosis was diagnosed in 47 (4.8%) in S arm and 81 (8.3%) pts in L arm (chi-square=9.88; p=0.002). Bone fractures occurred in 5 (0.5%) and 9 (0.9%) pts in S and L arm, respectively ( p=0.29, Fisher exact test). Conclusions: After 2-3 years of adjuvant tam, extended treatment with 5 years of letrozole resulted in significant improvement in DFS compared to the standard duration of 2-3 years of letrozole. Clinical trial information: NCT01064635.

Ofatumumab (OFA) Vs. Physician’s Choice (PC) of Therapy in Patients (pts) with Bulky Fludarabine Refractory (BFR) Chronic Lymphocytic Leukaemia (CLL): Results of the Phase III Study OMB114242

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4684-4684 ◽  
Author(s):  
Anders Österborg ◽  
Miklós Udvardy ◽  
Andrey Zaritskey ◽  
Per-Ola Andersson ◽  
Sebastian Grosicki ◽  
...  
Keyword(s):  
Research Funding ◽  
Phase Iii ◽  
Standards Of Care ◽  
Rank Test ◽  
P Value ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Phase Iii Study ◽  
Grade 3 ◽  
To Receive

Abstract OFA was approved for the treatment of fludarabine and alemtuzumab refractory CLL on the basis of a single-arm study which also included pts with BFR CLL. This open label, randomized, Phase III study of OFA or PC treatment in pts with CLL refractory to fludarabine and with bulky lymphadenopathy (at least one lymph node > 5 cm) was conducted to confirm the results of OFA in BFR pts and also through a 2nd randomization to compare extended OFA (12 months) vs. approved regimen of OFA (6 months). PC was considered an appropriate comparator for these pts given the lack of a consensus around standard of care treatment for this difficult-to-treat population. Pts were randomized 2:1 to receive either the approved regimen of 8 weekly infusions of OFA followed by 4 monthly infusions (Dose 1, 300 mg; Doses 2–12, 2000 mg) or PC of non-OFA containing therapy, including treatments approved for CLL and well established standards of care for up to 6 months. Pts in the OFA arm who had an investigator-assessed CR, PR or SD underwent a 2nd 2:1 randomization to 6 additional OFA infusions 2000 mg every 4 weeks (OFA Ext), or observation (Obs). Pts in the PC arm who developed disease progression during the study could receive OFA salvage therapy for up to 12 months of treatment. Premedication for OFA infusions consisted of glucocorticoid, paracetamol, and antihistamine. The primary objective of this study was to evaluate progression-free survival (PFS) with OFA treatment versus PC as assessed by an Independent Review Committee (IRC). Response assessments were performed using the 2008 Update of the NCI-WG CLL Guidelines [Hallek, 2008]. Secondary endpoints included overall response rate (ORR), time to next therapy (TNT), overall survival (OS), and safety. 122 pts were randomized (79 OFA, 43 PC). Pts completed a median of 12 OFA infusions and 3 months PC therapy. The median PFS (mPFS) as measured by IRC was 5.4 months for OFA and 3.6 months for PC (hazard ratio [HR] 0.79, p=0.27, stratified log rank test; Fig 1). Median PFS as assessed by the investigator (INV) was 7.0 months for OFA and 4.5 months for PC (HR 0.56, p=0.003). The median time to start of next anti-CLL treatment was 11.5 months for OFA and 6.5 months for PC (p=0.0004, stratified log rank test). The ORR (95% CI) by IRC evaluation was 38% (27%, 50%) for OFA and 16% (7%, 31%) for PC (p=0.02). 37 pts underwent a 2nd randomization to either OFA Ext (n=24) or Obs (n=13). From 2nd randomization, mPFS (INV) was 5.6 months for OFA Ext and 3.5 months for Obs (HR: 0.49, p=0.026, stratified log rank test) (Fig 2). Grade ³3 infusion reactions occurred in 5% of pts in the OFA arm with no fatal reactions in either arm. Grade ≥3 cytopenias in the OFA arm included neutropenia (24%, no prolonged neutropenia and 1 patient with late onset neutropenia), thrombocytopenia (8%), anemia (8%). Of the 43 PC pts, 22 received OFA Salvage with an ORR of 50% and mPFS of 5.4 months. Table of Response and Time to event Endpoints OFA (N=79) PC (N=43) Characteristics Median (range) Age, years 61.5 (46 – 82) 63 (40 – 76) No. prior therapies 4 (2 – 16) 3 (2 – 11) No. of infusions 12 (1 – 18) 3 (1 – 6) IRC Investigator Efficacy endpoints OFA PC p-value OFA PC p-value Responders, % 38% 16% 0.019 49% 37% 0.415 mPFS, months 5.36 3.61 0.267 7 4.5 0.003 OFA PC TNT, months 11.5 6.5 p=0.0004 OS, months 19.2 14.5 p=0.13 Figure 1. Kaplan-Meier Estimates of PFS by IRC (OFA vs. PC) Figure 1. Kaplan-Meier Estimates of PFS by IRC (OFA vs. PC) Figure 2. Kaplan-Meier Estimates of PFS by INV (OFA Ext vs. Obs from 2nd randomization) Figure 2. Kaplan-Meier Estimates of PFS by INV (OFA Ext vs. Obs from 2nd randomization) Conclusions: Although the study did not meet its primary endpoint of demonstrating statistically significant superior PFS by IRC, the ORR, PFS by investigator, TNT, and OS favor OFA and were consistent with previously reported results in BFR pts. There was also a longer PFS in pts who underwent the 2nd randomization to receive OFA Ext vs. the approved OFA treatment regimen of 6 months treatment. Disclosures Österborg: GSK: Research Funding. Off Label Use: Discussion of extended ofatumumab dosing (12 months) in addition to the approved 6 month dosing of ofatumumab in refractory CLL. Zaritskey:Novartis: Consultancy, Honoraria. Kaplan:GSK: Honoraria. Steurer:GSK: Consultancy, Honoraria, Research Funding. Schuh:GSK: Honoraria; Roche: Honoraria; Gilead: Honoraria; Celgene: Honoraria; Napp: Honoraria. Montillo:GSK: Honoraria. Kulyaba:GSK: Honoraria. Gorczyca:GSK: Employment. Daly:GSK: Employment. Chai-Ni:GSK: Employment. Lisby:Genmab: Employment. Gupta:GSK: Employment.

scholarly journals Sequencing of Androgen-Deprivation Therapy With External-Beam Radiotherapy in Localized Prostate Cancer: A Phase III Randomized Controlled Trial

2020 ◽  
Vol 38 (6) ◽  
pp. 593-601 ◽  
Author(s):  
Shawn Malone ◽  
Soumyajit Roy ◽  
Libni Eapen ◽  
Choan E ◽  
Robert MacRae ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
Localized Prostate Cancer ◽  
Definitive Treatment ◽  
Rank Test ◽  
Log Rank Test ◽  
Significant Difference ◽  
Grade 3

PURPOSE Dose-escalated radiotherapy (RT) with androgen-deprivation therapy (ADT) is a standard definitive treatment of localized prostate cancer (LPCa). The optimal sequencing of these therapies is unclear. Our phase III trial compared neoadjuvant versus concurrent initiation of ADT in combination with dose-escalated prostate RT (PRT). PATIENTS AND METHODS Patients with newly diagnosed LPCa with Gleason score ≤ 7, clinical stage T1b to T3a, and prostate-specific antigen < 30 ng/mL were randomly allocated to neoadjuvant and concurrent ADT for 6 months starting 4 months before RT (neoadjuvant group) or concurrent and adjuvant ADT for 6 months starting simultaneously with RT (concurrent group). The primary end point was biochemical relapse-free survival (bRFS). Stratified log-rank test was used to compare bRFS and overall survival (OS). Incidence of grade ≥ 3 late RT-related toxicities was compared by log-rank test. RESULTS Overall, 432 patients were randomly assigned to the neoadjuvant (n = 215) or concurrent group (n = 217). At 10 years, bRFS rates for the two groups were 80.5% and 87.4%, respectively. Ten-year OS rates were 76.4% and 73.7%, respectively. There was no significant difference in bRFS ( P = .10) or OS ( P = .70) between the two groups. Relative to the neoadjuvant group, the hazard ratio for the concurrent group was 0.66 (95% CI, 0.41 to 1.07) for bRFS and 0.94 (95% CI, 0.68 to 1.30) for OS. No significant difference was observed in the 3-year incidence of late RT-related grade ≥ 3 GI (2.5% v 3.9%) or genitourinary toxicity (2.9% v 2.9%). CONCLUSION In our study, there was no statistically significant difference in bRFS between the two treatment groups. Similarly, no difference was seen in OS or late RT-related toxicities. On the basis of these results, both neoadjuvant and concurrent initiations of short-term ADT with dose-escalated PRT are reasonable standards of care for LPCa.

scholarly journals Higher Coated-Platelet Levels are Associated with Stroke Recurrence following Nonlacunar Brain Infarction

2012 ◽  
Vol 33 (2) ◽  
pp. 287-292 ◽  
Author(s):  
Calin I Prodan ◽  
Julie A Stoner ◽  
Linda D Cowan ◽  
George L Dale
Keyword(s):  
Ischemic Stroke ◽  
Cumulative Incidence ◽  
Recurrent Stroke ◽  
Brain Infarction ◽  
Large Vessel ◽  
Rank Test ◽  
Stroke Recurrence ◽  
Additional Tool ◽  
Log Rank Test ◽  
Dual Agonist

Coated-platelets are procoagulant platelets observed upon dual-agonist stimulation with collagen and thrombin. Coated-platelet levels are elevated in patients with nonlacunar (large-vessel) ischemic stroke and decreased in patients with spontaneous intracerebral hemorrhage as compared with controls. The purpose of this study was to investigate a possible relationship between coated-platelet levels and stroke recurrence in patients with nonlacunar ischemic stroke. We assayed coated-platelet levels in 190 consecutive patients with nonlacunar stroke who were followed for up to 12 months; 20 subjects experienced recurrent stroke. Subjects were categorized into tertiles of coated-platelet levels. The distributions of time-to-recurrent stroke were estimated for each tertile using cumulative incidence curves and compared statistically using a log-rank test. The cumulative incidence of recurrent stroke at 12 months differed among the coated-platelet tertiles: 2% for the first tertile (lowest coated-platelet levels), 18% for the second tertile, and 17% for the third tertile (overall log-rank test, P = 0.019). These data suggest that higher levels of coated-platelets, measured shortly after a nonlacunar stroke, are associated with an increased incidence of stroke recurrence. This observation offers an additional tool for identifying patients at highest risk for stroke recurrence following a nonlacunar (large-vessel) infarct.

Improved Leukemia-Free Survival after Post-Consolidation Treatment with Histamine Dihydrochloride and Interleukin-2 in AML: A Randomized Phase III Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 261-261 ◽  
Author(s):  
Mats Brune ◽  
Sylvie Castaigne ◽  
John Catalano ◽  
Kurt Gehlsen ◽  
Wolf-Karsten Hofmann ◽  
...  
Keyword(s):  
Low Dose ◽  
Interleukin 2 ◽  
Phase Iii ◽  
Rank Test ◽  
Consolidation Therapy ◽  
Histamine Dihydrochloride ◽  
Free Survival ◽  
Consolidation Treatment ◽  
Log Rank Test ◽  
Significant Difference

Abstract Background: Histamine dihydrochloride (HDC) potentiates immune-based therapies by protecting pivotal anti-neoplastic lymphocytes from phagocyte-induced suppression. Previous results in AML indicated that post-consolidation treatment with HDC and low-dose interleukin-2 (IL-2) is safe and feasible, and that the combination may prolong leukemia-free survival (LFS). Aims: The primary objective was to determine if post-consolidation treatment with IL-2 and HDC could improve LFS for AML pts in complete remission (CR). Secondary objectives included overall survival (OS), LFS in CR1 and CR>1 subgroups, and safety. Methods: This international, randomized, open-label, phase III study was conducted at 92 centers. From June 1998 to October 2000, 320 AML pts [148 females, 172 males, median age 57 (18–84) yrs] were enrolled in CR after completion of standard consolidation therapy. Pts were stratified by CR1 or CR>1 and randomized to either treatment (n=160) or no treatment (control, n=160) arms. The treatment was self-administered at home and included 10 cycles of low-dose IL-2 (aldesleukin, Chiron Corp) 18 000 U/kg, sc bid plus HDC (Maxim Pharmaceuticals) 0.5 mg sc bid. For cycles 1–3, each cycle comprised 3 wks of treatment and 3 wks of rest, whereas in cycles 4–10 the rest periods were 6 wks. The study arms were well balanced with respect to age, sex, karyotype-based risk, time from CR to inclusion and frequency of secondary leukemia. Pts were followed for relapse and survival using an identical assessment schedule until 3 yrs after last enrollment. All efficacy analyses were intent-to-treat. Results: The median follow-up of living pts was 46 months. For the primary endpoint, treatment with HDC/IL-2 increased LFS in the entire study population (CR1/CR>1, n=320, p=0.026 stratified log-rank test). There was no significant difference in OS (p=0.33). In the analysis of pre-stratified subgroups, one pt was excluded. For CR1 pts (n=262), HDC/IL-2 significantly improved LFS (p=0.011, log-rank test), with 3-year Kaplan-Meier estimates of 26% (control group) and 40% (treatment group). The difference in OS did not reach significance (p=0.16). For CR>1 pts (n=57), outcome was not affected by treatment. Side effects attributable to IL-2 included fever and local inflammatory reactions. HDC treatment induced symptoms of transient vasodilatation. Serious adverse events occurred in approximately 20% of pts in both groups. There were no treatment-related deaths. Conclusions: For AML pts in CR, post-consolidation therapy with HDC and IL-2 was safe and significantly improved LFS compared to standard of care. The benefit observed of HDC/IL-2 treatment appears to be explained by a reduction of relapses in CR1 pts.

Phase III Trial of All-Trans Retinoic Acid (ATRA) vs Daunorubicin (D) and Cytosine Arabinoside (A) as Induction Therapy and ATRA vs Observation as Maintenance Therapy for Children with Newly Diagnosed Acute Promyelocytic Leukemia (APL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 894-894
Author(s):  
John Gregory ◽  
Haesook Kim ◽  
Todd Alonzo ◽  
Rob Gerbing ◽  
Angela Ogden ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Maintenance Therapy ◽  
Pseudotumor Cerebri ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
All Trans Retinoic Acid ◽  
Female Predominance ◽  
One Year ◽  
To Receive ◽  
Salvage Rate

Abstract Between April 1992 and February 1995, 71 children with locally diagnosed APL were enrolled on the national trial (ECOG E2491) to test ATRA during induction and maintenance (MAINT). Induction consisted of either ATRA, 45 mg/m2/d orally, or 1–2 cycles of D, 45 mg/m2/d IV bolus days 1–3, plus A, 100 mg/m2/day by continuous intravenous (IV) infusion days 1–7. All patients (pts) achieving complete remission (CR) were scheduled to receive two cycles of consolidation chemotherapy consisting of one cycle the same as induction followed by A, 2 gm/m2 IV over one hour every 12 hours days 1–4, plus D, 45 mg/m2/d IV bolus days 1–2. Pts on both arms were then randomized to receive either MAINT ATRA, 45 mg/m2/d orally for one year, or observation (OBS). Fifty-three children with the (15;17) translocation or centrally reviewed M3 FAB APL are the subject of this report. These patients were aged 1–18 years (median 12 years; only 2 &lt; 2 yrs). A female predominance was noted (60% female). The distribution by race was: White 35, African American 7, Hispanic 8, Asian 2, and Filipino 1 patient. No extramedullary disease was proven at diagnosis. Twenty-seven patients were reported to have bleeding symptoms at diagnosis. The median WBC at study entry was 3.2 (4.2 for the DA arm, 2.6 for the ATRA arm). Only one patient was noted to have the M3v subtype. Twenty-seven pts were treated on the ATRA induction arm and 26 on the DA induction arm. A CR rate of 70% was obtained (ATRA CR 81%, DA CR 58%, P=0.08) after Induction and 3 additional patients achieved a CR after cross-over to DA (overall CR=75%). The 3 year DFS from achieving CR was 49% (DA 46%, ATRA 51%, P=0.33). Thirty-three patients reached maintenance therapy after CR- 16 in the OBS arm and 17 in the MAINT ATRA arm. The 3 year DFS from the start of MAINT was 48%( MAINT ATRA 75%, OBS 19%, P=0.0001). The 5 year OS was 68% (DA 62%, ATRA 73%, P=0.33). Induction toxicity data for 53 patients treated on this study included: four patients had a Grade III/IV hemorrhage during induction (DA 3, ATRA 1), intracranial hemorrhage(ICH) in 3, retinoic acid syndrome (RAS) in 2, pseudotumor cerebri definite in 2 and probable in 6, typhlitis in 2, and pancreatitis in 1. Four lethal toxicities occurred including two from ICH and one each from infection and RAS. (DA 3, ATRA 1) In conclusion, 1) the outcome for children with APL is excellent when treated with ATRA and anthracycline-based induction; 2) ATRA as maintenance resulted in a statistically significant advantage in DFS; 3) the salvage rate for relapsed patients appeared promising.

Sign in / Sign up

Export Citation Format

Share Document