De-intensified chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma based on plasma EBV DNA: A phase 2 randomized noninferiority trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 110-110
Author(s):  
Hai-Qiang Mai ◽  
Xiao Yun Li ◽  
Hao-Yuan Mo ◽  
Guo Ling ◽  
Dong-Hua Luo ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Controlled Trial ◽  
Phase Iii ◽  
Stage Iii ◽  
Phase 2 ◽  
Significant Difference ◽  
Ebv Dna ◽  
Grade 3 ◽  
Cycle Group ◽  
To Receive

110 Background: The cisplatin-based chemoradiotherapy (CCRT), given at a dose of 100 mg/m2 for 3 cycles during radiotherapy, is the major treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). As several retrospective studies showed that receiving a cumulative cisplatin dose of 200 mg/m2 can bring survival benefits to NPC patients, we sought to test the non-inferiority of 2-cycle concurrent cisplatin over 3-cycle in locoregionally advanced NPC with Epstein-barr virus (EBV) DNA levels < 4000 copies/ml. Methods: We did a non-inferiority, phase 2, randomised controlled trial. Patients were enrolled with stage III–IVB NPC, EBV DNA levels < 4000 copies/ml, aged 18–70 and adequate haematological, renal, and hepatic function. Eligible patients were randomly assigned (1:1) to receive 2 or 3 cycles of cisplatin-based CCRT. Patients in the 2-cycle group were scheduled to receive 100 mg/m2 cisplatin given every 3 weeks concurrently with radiotherapy, and patients in the 3-cycle group received 100 mg/m2 cisplatin given every 3 weeks for 3 cycles. Randomization was done by a computer-generated random number code with a block size of six, stratified by clinical stage III or IV. The primary endpoint was 3-year progression-free survival (PFS), with a non-inferiority margin of 10%. This study was registered with ClinicalTrials.gov, ID. NCT02871518. Results: Between September 2016 and October 2018, 342 patients were enrolled, of whom 332 were randomly assigned to receive 2 or 3 cycles of cisplatin. 314 (94.6%) patients completed protocol-defined cycles of chemotherapy. After median follow-up of 33.6 months, 20 (12.0%) patients in the 2-cycle group and 17 (10.2%) patients in the 3-cycle group had tumor progression, and the 3-year PFS rates were 88.0% and 90.4% respectively, with a difference of 2.4% (95%CI -4.3 to 9.1, Pnon-inferiority < 0.001). In the per-protocol analysis, 3-year PFS was 88.5% in the 2-cycle group and 90.6% in the 3-cycle group, with a difference of 2.1% (95% CI –4.7 to 8.9; Pnon-inferiority= 0.001). No significant difference was observed concerning OS, LRRFS and DMFS. The grade 3 or 4 acute adverse events were recorded in 113 (68.1%) patients in the 2-cycle group and 116 (69.9%) patients in the 3-cycle group. Patients in the 3-cycle group was observed to have significantly more hyponatremia. Besides, patients in the 3-cycle group presented with more grade 1 or 2 dry mouth, dysphagia, weight loss, fatigue, constipation, fever, mucositis and dermatitis. More grade 3 or 4 anorexia, mucositis and dermatitis were also recorded in the 3-cycle group. No patients died from treatment-related toxicities. Conclusions: IMRT plus 2 cycles of concurrent 100 mg/m2 cisplatin could be an alternative option for patients with low-risk locoregionally advanced NPC. Further phase III studies are needed to validate the findings of this study. Clinical trial information: NCT02871518.

A phase III study of Æ-941 with induction chemotherapy (IC) and concomitant chemoradiotherapy (CRT) for stage III non- small cell lung cancer (NSCLC) (NCI T99–0046, RTOG 02–70, MDA 99–303)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7527-7527 ◽  
Author(s):  
C. Lu ◽  
J. J. Lee ◽  
R. Komaki ◽  
R. S. Herbst ◽  
W. K. Evans ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Performance Status ◽  
Stage Iiib ◽  
Phase Iii ◽  
Stage Iii ◽  
Type I ◽  
Eligibility Criteria ◽  
Unresectable Stage ◽  
Significant Difference ◽  
Stage Iii Nsclc

7527 Background: Æ-941 is a shark cartilage extract with antiangiogenic properties. We conducted a placebo-controlled trial testing Æ-941, with IC and CRT, in unresectable stage III NSCLC. Methods: Eligibility criteria included performance status (PS) < 2, weight loss < 10%. Subjects received one of two treatment regimens depending on site of enrollment: carboplatin (C) (AUC 6) and paclitaxel (P) (200 mg/m2) × 2 cycles followed by CRT (60 Gy/30 fractions) with weekly C (AUC 2) and P (45 mg/m2) × 6 doses or cisplatin (CDDP) (75 mg/m2, d1) and vinorelbine (V) (30 mg/m2, d1 and 8) × 2 cycles followed by CRT (60 Gy/30 fractions) with CDDP (75 mg/m2, day 1) and V (15 mg/m2, d1 and 8) × 2 cycles. Subjects were randomized to receive Æ-941 (Arm A) or placebo (Arm B), 120 mL orally twice daily, at the start of IC and continuing after CRT as maintenance therapy. Randomization was stratified for stage, gender, and type of chemotherapy. The primary endpoint was overall survival (OS), with a planned sample size of 756 subjects providing 80% power to detect a 25% difference in OS, assuming a control arm median survival time (MST) of 13 months, type I error 0.05. Results: Between 6/00 and 2/06, 384 subjects were enrolled onto the trial and randomized. In 2/06 the trial was closed to new patient entry due to insufficient accrual. This final analysis is based on 379 randomized and eligible subjects (188 arm A, 191 arm B). Subject characteristics: 60% male, median age 63 years (range 37–84), 56% stage IIIB, 58% C-based chemotherapy, median follow-up 3.7 years. There was no significant difference in OS between arms A and B, with MSTs of 14.4 (95% CI 12.6–17.9) and 15.6 (95% CI 13.8–18.1) months, respectively (log-rank p=0.73). OS by pre-specified stratification factors: stage IIIB vs IIIA (MST 13.9 vs. 17.4 months, p=0.25), C vs. CDDP chemotherapy (MST 14.4 vs. 16.7 months, p=0.13), and male vs. female (MST 15.7 vs. 15.1 months, p=0.74). The study drug was well tolerated. Fewer subjects in arm A experienced grade 3 or higher adverse events (66% vs. 77%, p=0.018). Conclusions: The addition of Æ−941 to IC and CRT does not improve OS in patients with unresectable stage III NSCLC. No significant financial relationships to disclose.

Results of a phase III randomized controlled trial of the safety and efficacy of atrasentan in men with nonmetastatic hormone-refractory prostate cancer (HRPC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5018-5018 ◽  
Author(s):  
J. B. Nelson ◽  
J. L. Chin ◽  
W. Love ◽  
C. Schulman ◽  
D. Sleep ◽  
...  
Keyword(s):  
Disease Progression ◽  
Nasal Congestion ◽  
Controlled Trial ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Bone Alkaline Phosphatase ◽  
Phase Iii ◽  
Significant Difference ◽  
Hormone Refractory ◽  
To Receive

5018 Introduction: Atrasentan is a potent oral, selective endothelin A receptor antagonist with biological activity in patients with HRPC. This randomized phase III trial of atrasentan vs placebo was conducted in 941 men with nonmetastatic HRPC whose prostate-specific antigen (PSA) was rising despite adequate androgen suppression. Methods: 467 patients were randomized to receive atrasentan 10 mg and 474 patients were randomized to receive placebo daily. Primary efficacy endpoints were time to disease progression (TTP) and progression-free survival, with progression defined as the onset of metastases. Secondary endpoints were overall survival, time to PSA progression, change from baseline in bone alkaline phosphatase (BAP), and PSA doubling time (PSADT). Results: In the intent-to-treat population, median TTP was 764 days with atrasentan and 671 days with placebo (hazard ratio [HR], 0.915; G1,1 P=0.288). More placebo- treated patients (267, 56.3%) than atrasentan-treated patients (227, 48.6%) experienced disease progression. Overall, 278 patients (29.5%) discontinued before reaching a protocol-defined endpoint (155, 40.8% US vs 123, 21.6% non-US). More placebo-treated patients (210, 44.3%) than atrasentan-treated patients (169, 36.2%) experienced new skeletal lesions. Median survival was 1,477 days for the atrasentan group and 1,403 days for the placebo group (HR, 0.909; G1,1 P=0.176). Mean change from baseline to final BAP was -1.51 IU/L with atrasentan compared with +2.20 IU/L with placebo (P<0.001). PSADT was lengthened with atrasentan relative to placebo (P<0.031). The incidence of peripheral edema, nasal congestion, headache, dyspnea, anemia, and heart failure was significantly greater in the atrasentan group (P<0.05). Most of these events were mild and nonserious and did not result in study discontinuation. Conclusions: Data from this study did not show a statistically significant difference in time to progression between atrasentan and placebo. However, the high discontinuation rate, especially among US patients, may have compromised the ability of the study to accurately determine the treatment effect of atrasentan in this population. No significant financial relationships to disclose.

Phase III Randomized Trial of FOLFIRI Versus FOLFOX4 in the Treatment of Advanced Colorectal Cancer: A Multicenter Study of the Gruppo Oncologico Dell’Italia Meridionale

2005 ◽  
Vol 23 (22) ◽  
pp. 4866-4875 ◽  
Author(s):  
Giuseppe Colucci ◽  
Vittorio Gebbia ◽  
Giancarlo Paoletti ◽  
Francesco Giuliani ◽  
Michele Caruso ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Bolus Injection ◽  
Advanced Colorectal Cancer ◽  
Phase Iii ◽  
Significant Difference ◽  
Duration Of Response ◽  
Phase Iii Study ◽  
The Difference ◽  
Grade 3 ◽  
To Receive

Purpose We performed this phase III study to compare the irinotecan, leucovorin (LV), and fluorouracil (FU) regimen (FOLFIRI) versus the oxaliplatin, LV, and FU regimen (FOLFOX4) in previously untreated patients with advanced colorectal cancer. Patients and Methods A total of 360 chemotherapy-naive patients were randomly assigned to receive, every 2 weeks, either arm A (FOLFIRI: irinotecan 180 mg/m2 on day 1 with LV 100 mg/m2 administered as a 2-hour infusion before FU 400 mg/m2 administered as an intravenous bolus injection, and FU 600 mg/m2 as a 22-hour infusion immediately after FU bolus injection on days 1 and 2 [LV5FU2]) or arm B (FOLFOX4: oxaliplatin 85 mg/m2 on day 1 with LV5FU2 regimen). Results One hundred sixty-four and 172 patients were assessable in arm A and B, respectively. Overall response rates (ORR) were 31% in arm A (95% CI, 24.6% to 38.3%) and 34% in arm B (95% CI, 27.2% to 41.5%; P = .60). In both arms A and B, median time to progression (TTP; 7 v 7 months, respectively), duration of response (9 v 10 months, respectively), and overall survival (OS; 14 v 15 months, respectively) were similar, without any statistically significant difference. Toxicity was mild in both groups: alopecia and gastrointestinal disturbances were the most common toxicities in arm A; thrombocytopenia and neurosensorial were the most common toxicities in arm B. Grade 3 to 4 toxicities were uncommon in both arms, and no statistical significant difference was observed. Conclusion There is no difference in ORR, TTP, and OS for patients treated with the FOLFIRI or FOLFOX4 regimen. Both therapies seemed effective as first-line treatment in these patients. The difference between these two combination therapies is mainly in the toxicity profile.

Similar Efficacy and Toxicity Profile for Idarubicine and Mitoxantrone in Induction and Intensification Treatment of Children with Acute Myeloid Leukemia (AML) or Myelodysplasia (MDS): Long-Term Results of the EORTC-CLG Randomized Phase III Trial 58921

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2615-2615 ◽  
Author(s):  
Barbara De Moerloose ◽  
Stefan Suciu ◽  
Martine Munzer ◽  
Caroline Piette ◽  
Karima Yakouben ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Late Onset ◽  
Standard Dose ◽  
Phase Iii ◽  
Long Term Results ◽  
High Dose ◽  
Sibling Donor ◽  
Significant Difference ◽  
Grade 3 ◽  
To Receive

Abstract Abstract 2615 Background: The first EORTC-CLG AML pilot study (58872) demonstrated the efficacy of Mitoxantrone (MTZ), substituted for daunorubicin, in the treatment of childhood AML. The subsequent trial (58921) aimed to compare MTZ and Idarubicin (IDA), an anthracycline with a favorable pharmacokinetic profile (such as good CSF penetration) and suggested to be more efficacious than daunorubicin in adult AML trials performed in the last two decades. Methods: Between March 1993 and December 2002, 227 eligible patients (pts) <18y of age with newly diagnosed AML (N=216) or high risk MDS (RAEB & RAEBt, N=11) were randomized in the EORTC phase III 58921 trial to receive either IDA or MTZ in induction and 1st intensification course, each at a dose of 10 mg/m2/d for 3 days in both courses. Concomitant chemotherapy consisted of standard dose Cytarabine (AraC) and Etoposide (Eto) in induction and high-dose AraC (18–36 g/m2) in 1st intensification. Allogeneic stem cell transplantation after 1st intensification was recommended for pts who achieved CR and had an HLA-identical sibling donor. Patients in CR without donor had to receive a 2nd (DCTER = continuous infusion of standard dose AraC, Daunorubicin 4x 20 mg/m2/d, Eto, Dexamethasone, 6-thioguanine) and 3rd intensification course (high dose AraC 12 g/m2 + Eto), followed by maintenance therapy (6-Thioguanine daily + AraC 4 days/month) for 12 months. CNS irradiation after the 3rd intensification for patients with initial WBC counts >=70×10E9/L was abandoned from November 1994 on. Randomization was done centrally. The primary endpoint was EFS; secondary endpoints were OS, CR rate after induction/1st intensification, DFS and toxicity. Intention-to-treat analysis was used. Results: A total of 112 and 115 eligible pts were randomly assigned to receive IDA and MTZ, respectively. The rate of CR after two courses was 79.5% (IDA) vs 85.2% (MTZ). At an overall median follow-up of 9.9 y (range 0.25–16 y), there were 65 vs 59 events in the IDA vs MTZ group: failure to achieve CR (23 vs 17), relapse (35 vs 40), and death without relapse (7 vs 2). The 5-year EFS rate was 42.0% (SE 4.7%) in the IDA group and 48.4% (SE 4.7%) in the MTZ group (hazard ratio (HR) = 1.20, 95% CI 0.84–1.71, 2-sided log rank p=0.29). The 5-year OS rate was comparable in both treatment arms: 59.8% (SE 4.6%) in the IDA group and 57.5% (SE 4.7%) in the MTZ group (HR = 1.03, 95% CI 0.70–1.54, 2-sided log rank p=0.87). In CR patients with (N=46/187) or without (N=141/187) an HLA-identical sibling donor, the 5-year DFS rate from CR was 65.1% (SE 7.1%) and 51.5% (SE 4.2%) respectively (HR=0.65, 95% CI 0.37–1.11, 2-sided log rank p=0.11) and the 5-year OS rate 78.0% (SE 6.1%) and 60.7% (SE 4.1%) respectively (HR=0.53, 95% CI 0.28–1.01, 2-sided log rank p=0.048). This advantage for patients with a donor remained important regarding both DFS (HR=0.60, p=0.07) and OS (HR=0.49, p=0.03), even after adjustment for WBC count at diagnosis, age, cytogenetic features and randomized arm. The interval between start of induction and start of 1st intensification was similar in both arms (median 5.2 weeks). Grade 3–4 infection following the induction course was 37.5% (IDA) vs 25.4% (MTZ); incidence of fever grade 3–4 was 25% (IDA) vs 22.8% (MTZ). In this trial, the cumulative anthracycline dosage (conversion factor 5) was 380 mg/m2. Acute and late-onset cardiotoxicity was comparable in both treatment arms. Conclusion: There was no significant difference in efficacy and in toxicity between the two randomized treatment groups, IDA versus MTZ, although grade 3–4 infection rate following the induction course was slightly higher in the IDA arm. Patients who reached CR and who had a HLA compatible sibling donor had a longer DFS and OS than pts without a donor. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Randomized Controlled Trial: Neostigmine for Intra-abdominal Hypertension in Acute Pancreatitis

2021 ◽  
Author(s):  
Wenhua He ◽  
Peng Chen ◽  
Yupeng Lei ◽  
Liang Xia ◽  
Pi Liu ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Conventional Treatment ◽  
Controlled Trial ◽  
Phase Iii ◽  
Abdominal Pressure ◽  
Double Blind ◽  
Phase Iii Trial ◽  
Abdominal Hypertension ◽  
Significant Difference ◽  
To Receive

Abstract Background: Intra-abdominal hypertension (IAH) in acute pancreatitis (AP) is associated with deterioration in organ function. This trial aimed to assess the efficacy of neostigmine for IAH in patients with AP.Methods: In this single-centre, randomized trial, consenting patients with IAH within 2 weeks of AP onset received conventional treatment for 24 hours. Patients with sustained intra-abdominal pressure (IAP) ≥ 12 mmHg were randomized to receive intramuscular neostigmine (1 mg every 12 hours increased to every 8 hours or every 6 hours, depending on response) or continue conventional treatment for 7 days. The primary outcome was the change of IAP after randomization. Results: A total of 80 patients were recruited to neostigmine (n = 40) or conventional treatment (n = 40). There was no significant difference in baseline parameters. IAP levels were significantly lower in neostigmine group than conventional treatment group at 9 hour (13.8 ± 3.5 vs 15.0 ± 3.1, P = 0.038), 15 hour (13.3 ± 3.4 vs 14.7 ± 3.1, P = 0.015), and 168 hour (12.2 ± 2.7 vs 13.6 ± 3.5, P = 0.045) after randomisation. This effect was more pronounced in patients with baseline IAP ≥ 15 mmHg (all P ≤ 0.038). Stool volume was consistently higher in the neostigmine group during the 7-day period (all P < 0.05). Other secondary outcomes were not significantly different between the two groups.Conclusion: Neostigmine reduced IAP and promoted defecation in patients with AP and IAH. These results warrant a larger, placebo-controlled, double-blind phase III trial.Trial registration: Clinical Trial No: NCT02543658 (registered August /27, 2015). https://clinicaltrials.gov/ct2/show/NCT02543658

A double-blind placebo-controlled trial of perioperative prophylactic antibiotics for elective neurosurgery

1988 ◽  
Vol 69 (5) ◽  
pp. 687-691 ◽  
Author(s):  
Ross Bullock ◽  
James R. van Dellen ◽  
William Ketelbey ◽  
S. Gustav Reinach
Keyword(s):  
Controlled Trial ◽  
Prophylactic Antibiotics ◽  
Risk Of Infection ◽  
Broad Spectrum Antibiotic ◽  
Wound Sepsis ◽  
Double Blind ◽  
Content Type ◽  
Exact Test ◽  
Significant Difference ◽  
To Receive

✓ In this study, 417 patients undergoing “clean” elective neurosurgical operative procedures were randomized to receive a broad-spectrum antibiotic (piperacillin) or placebo given as three perioperative doses, each 6 hours apart. Randomization was carried out by hospital pharmacists, and the investigators remained blinded until the end of the study. Twenty cases were excluded from analysis because either an unforeseen second operation was performed or antibiotic therapy was initiated within 30 days after surgery to treat infection or the risk of infection. Twelve of the 205 patients treated with placebo developed postoperative wound sepsis, and four of the 192 piperacillin-treated patients developed wound sepsis — a statistically significant difference (p < 0.05, Fisher's exact test). Piperacillin thus appeared to reduce the incidence of neurosurgical wound infection in this study.

scholarly journals Long Term Outcome of Lenalidomide-Dexamethasone (Rd) Vs Melphalan-Lenalidomide-Prednisone (MPR) Vs Cyclophosphamide-Prednisone-Lenalidomide (CPR) As Induction Followed By Lenalidomide-Prednisone (RP) Vs Lenalidomide (R) As Maintenance in a Community-Based Newly Diagnosed Myeloma Population: Updated Analysis of EMN01 Phase III Study

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 901-901
Author(s):  
Sara Bringhen ◽  
Massimo Offidani ◽  
Pellegrino Musto ◽  
Anna Marina Liberati ◽  
Giulia Benevolo ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Phase Iii ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Community Based ◽  
Advisory Committees ◽  
Risk Of Death ◽  
Grade 3 ◽  
To Receive

Abstract Introduction : Rd and MPR showed to be effective combinations in elderly newly diagnosed multiple myeloma (NDMM) patients (pts). Cyclophosphamide is a less toxic alkylating alternative agent. EMN01 is the first trial to formally compare these three different Lenalidomide-based combinations. Maintenance with Lenalidomide has been recently approved in patients eligible for autologous stem cell transplant (ASCT). Few data are available about the best combination as maintenance in patients not eligible for ASCT. Methods : 662 pts with NDMM were randomized to receive 9 28-day cycles of Rd (lenalidomide 25 mg/day for 21 days; dexamethasone 40 mg on days 1,8,15 and 22 in pts 65-75 years old and 20 mg in those &gt;75 years), MPR (lenalidomide 10 mg/day for 21 days; melphalan orally 0.18 mg/Kg for 4 days in pts 65-75 years old and 0.13 mg/Kg in &gt;75 years pts; prednisone 1.5 mg/Kg for 4 days) or CPR (lenalidomide 25 mg/day for 21 days; cyclophosphamide orally 50 mg/day for 21 days in pts 65-75 years old and 50 mg every other day in &gt;75 years pts; prednisone 25 mg every other day). After induction, pts were randomized to receive maintenance with lenalidomide alone (R; 10 mg/day for 21 days) or with prednisone (RP; R, 10 mg/day for 21 days and P, 25 mg every other day), until disease progression. Results : Pts characteristics were well balanced in all groups; 217 pts in Rd, 217 in MPR and 220 in CPR arms could be evaluated. After a median follow-up of 63.7 months, median PFS was 23.2 months in MPR, 18.9 months in CPR and 18.6 months in Rd (MPR vs CPR p=0.02; MPR vs Rd p=0.08). Median overall survival (OS) was 79.9 months in MPR, 69.4 months in CPR and 68.1 months in Rd (MPR vs CPR p=0.98; MPR vs Rd p=0.64). The most common grade ≥3 adverse event (AEs) was neutropenia: 64% in MPR, 29% in CPR and 25% in Rd pts (p&lt;0.0001). Grade ≥3 non hematologic AEs were similar among arms. At the end of induction, 402 pts were eligible for maintenance, 198 in the RP and 204 in the R groups. PFS from start of maintenance was 22.2 months in the RP group and 17.6 in the R group, with 20% reduced the risk of death/progression for pts receiving RP maintenance (HR 0.81, p=0.07; Figure 1). A subgroup analysis was performed to determine the consistency of RP vs R treatment effect in different subgroups using interaction terms between treatment and cytogenetic abnormalities, ISS, age, sex, induction treatment and response before maintenance (Figure 1). No difference in OS was observed (HR 1.02, p=0.93) but the OS analysis was limited by the low number of events. Median duration of maintenance was 23.0 months in RP pts and 20.5 months in R pts, 14% and 13% of pts discontinued due to AEs, in RP and R groups, respectively. Conclusion : This phase III trial compared 2 different Lenalidomide-containing induction regimens and 2 different Lenalidomide-containing maintenance regimens in an elderly community-based NDMM population. MPR prolonged PFS by approximately 5 months, yet the higher incidence of hematologic toxicity should be carefully considered. The addition of low-dose prednisone to standard lenalidomide maintenance reduced the risk of death/progression by 20%, with a good safety profile. Updated results will be presented at the meeting. Disclosures Bringhen: Mundipharma: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Celgene: Honoraria; Bristol Myers Squibb: Honoraria; Karyipharm: Membership on an entity's Board of Directors or advisory committees. Offidani: celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Musto: Celgene: Honoraria; Janssen: Honoraria. Gaidano: Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Roche: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. De Sabbata: Celgene: Membership on an entity's Board of Directors or advisory committees. Palumbo: Sanofi: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Binding Site: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria, Research Funding; Genmab A/S: Consultancy, Honoraria, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Employment, Equity Ownership, Honoraria, Research Funding. Hájek: Amgen, Takeda, BMS, Celgene, Novartis, Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria; Pharma MAR: Consultancy, Honoraria. Boccadoro: Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; AbbVie: Honoraria; Mundipharma: Research Funding; Sanofi: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding.

scholarly journals Prevalence of Epstein Barr Virus in biopsy specimens of nasopharyngeal carcinoma from Serbian patients

2014 ◽  
Vol 66 (2) ◽  
pp. 537-544 ◽  
Author(s):  
Ana Banko ◽  
Ivana Lazarevic ◽  
M. Folic ◽  
Maja Cupic ◽  
Tanja Jovanovic
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Biopsy Specimens ◽  
C Terminus ◽  
Geographical Regions ◽  
Significant Difference ◽  
Ebv Dna ◽  
Epstein Barr

The development of nasopharyngeal carcinoma (NPC) is the result of interaction between Epstein-Barr Virus (EBV) and many non-viral factors. The aims of this study were to determine the prevalence of EBV in NPC biopsies from Serbian patients and to investigate the correlation between EBV presence and demographic, anamnestic and clinical data. Ninety-three tissue blocks were included. For detection of EBV DNA, the C terminus of the LMP1 gene was amplified by nested-PCR. Twenty-eight biopsies were EBV-DNA-positive (30.1%), with a statistically significant difference in EBV DNA presence between geographical regions (p=0.02) and between the stages of tumor-node-metastasis (TNM) (p=0.02). A correlation was also found with the presence of EBV DNA and smoking (p=0.02). The correlation of EBV DNA presence, with or without smoking and the promising outcome of the disease was statistically significant (p=0.02; p=0.01). The EBV DNA findings from this study confirm the role of EBV in NPC carcinogenesis, and show the different distribution among TNM stages and correlation between the virus and outcome of disease.

A phase III multicenter randomized clinical trial to compare cisplatin plus fluorouracil with or without docetaxel as the first-line induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma: Long-term outcomes update.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6032-6032
Author(s):  
Wang Fang FangZheng
Keyword(s):  
Clinical Trial ◽  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Phase Iii ◽  
Karnofsky Performance Score ◽  
Long Term Outcomes ◽  
First Line ◽  
Grade 3

6032 Background: A phase III multicenter prospective randomized controlled trial was conducted to compare cisplatin plus 5-fluorourcil with or without docetaxel as first-line induction chemotherapy in the patients with locoregionally advanced nasopharyngeal carcinoma (LANPC). Here, we report on the long-term outcomes and late toxicities of the trial (NCT01536223). Methods: Patients with newly diagnosed LANPC, stage III-IV disease, Karnofsky performance score≥70, without metastasis were eligible and randomly assigned 1:1 to TPF versus PF for three cycles. The primary end point was progression-free survival; local control, OS and advent events were important key secondary end points. The Kaplan-Meier method and the log-rank test were used to conduct and compare the survival curves in this study. Results: Two hundred ninety-nine patients were enrolled. 276 patients (138 TPF and 138 PF) were evaluable. Baseline characteristics were well-balanced between two groups, and the median age was 48 (range, 18-60 years). The ORR rates after induction chemotherapy and chemoradiotherapy were 90.6% and 9797.8% in TPF group and 87.0% (P > 0.05) and 97.8% (P > 0.05), respectively. The median follow-up was 99 months. For all patients, the 5- and 8-year OS and PFS were 76.9% and 74.9%, 72.3% and 69.1%, respectively. PF was associated with a similar PFS versus TPF ( 5-year PFS of 72.4% versus 73.2%, P =.747), and an equivalent OS at 5 years ( 79.2% and 79.1%, P = 0.519). Treatment-related grade 3 to 4 advent events were less frequent with PF compared with TPF. Conclusions: With prolonged follow-up, the survival outcomes in the PF group were not non-inferiority to those in the TPF group, but grade 3 to 4 advent events were less frequent. Clinical trial information: NCT01536223.

Crossover and rechallenge with pembrolizumab in recurrent patients from the EORTC 1325-MG/Keynote-054 phase 3 trial, pembrolizumab versus placebo after complete resection of high-risk stage III melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9500-9500
Author(s):  
Alexander M. Eggermont ◽  
Andrey Meshcheryakov ◽  
Victoria Atkinson ◽  
Christian U. Blank ◽  
Mario Mandalà ◽  
...  
Keyword(s):  
Disease Progression ◽  
Objective Response ◽  
Stage Iv ◽  
Median Number ◽  
Complete Resection ◽  
Stage Iii ◽  
Phase 3 ◽  
Double Blind ◽  
Grade 3 ◽  
To Receive

9500 Background: The phase 3 double-blind EORTC 1325/KEYNOTE-054 trial evaluated pembrolizumab (pembro) vs placebo in stage III cutaneous melanoma patients (pts) with complete resection of lymph nodes. Pembro improved RFS (hazard ratio [HR] 0.57) and DMFS (HR 0.60) (Eggermont, NEJM 2018, TLO 2021). In the pembro group, the incidence of immune related AE (irAE) grade 1-5 was 37%, and of grade 3-5 was 7%. We present the safety profile, response rate and PFS for the subset of pts who had a recurrence and crossed over or were rechallenged with pembrolizumab, within protocol. Methods: Pts were randomized to receive iv. pembro 200 mg (N=514) or placebo (N=505) every 3 weeks for a total of 18 doses (~1 year). Upon recurrence with no brain metastases, pts with an ECOG PS 0-2 were eligible to enter part 2 of the study, i.e. to receive pembro 200 mg iv. every 3 weeks for a maximum of 2 years, for crossover (those who received placebo) or rechallenge (those who recurred ≥6 months after completing one year of pembro therapy). Treatment was stopped in case of disease progression (RECIST 1.1) or unacceptable toxicity. Results: At the clinical cut-off (16-Oct-2020), 298 (59%) pts had a disease recurrence in the placebo group; 155 pts participated in the crossover part 2 of the trial. A total of 297 (58%) pts completed the 1-yr pembro adjuvant treatment, of whom 47 had a recurrence ≥6 mths from the stop of treatment and 20 entered in the rechallenge part of the trial. Among 175 pts who started pembro in Part 2, 160 discontinued due to completion of therapy (N=24), disease progression (N=88), toxicity (N=20), investigator's decision (N=21), or other reason (N=7); 15 pts were still on-treatment. Results for the 2 groups are provided in the table. The median number of doses was 12 and 5.5, respectively (resp), and the median follow-up was 41 and 19 mts, resp. Among the 175 pts, 51 (29%) had a grade 1-4 irAE (by group: 47 [30%] and 4 [20%] resp) and 11 (6%) a grade 3-4 irAE. Conclusions: Pembrolizumab treatment after crossover yielded a 39% ORR in evaluable pts and an overall 3-yr PFS of ̃32%, but after rechallenge the efficacy was lower. Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA The median PFS (95% CI) from start of Part 2 was 14 (5-27) and 8 (5-15) mts for stage III-resected and III/IV various, resp. Among the 80 stage IV crossover pts with evaluable disease, 31 (39%) had an objective response: 14 (18%) CR, 17 (21%) PR. The 2-yr PFS rate from response was 69% (95% CI 48-83%). For these 80 pts, the median PFS was 6.1 mts and the 3-yr PFS rate was 31% (95% CI 21-41%). Among 9 stage IV rechallenged pts with an evaluable disease, 1 (11%) reached CR, 3 had SD and 5 PD. Clinical trial information: NCT02362594. [Table: see text]

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