Adding Mercaptopurine and Methotrexate to Alternate Week ATRA Maintenance Therapy Does Not Improve the Outcome for Adults with Acute Promyelocytic Leukemia (APL) in First Remission: Results From North American Leukemia Intergroup Trial C9710

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 258-258 ◽  
Author(s):  
Bayard L. Powell ◽  
Barry K Moser ◽  
Wendy Stock ◽  
Robert E. Gallagher ◽  
Cheryl L Willman ◽  
...  
Keyword(s):  
Adverse Events ◽  
Maintenance Therapy ◽  
Arsenic Trioxide ◽  
Risk Group ◽  
Statistical Significance ◽  
Phase Iii ◽  
Consolidation Therapy ◽  
Number Of Patients ◽  
First Remission ◽  
Grade 3

Abstract Abstract 258 This randomized phase III clinical trial was designed to evaluate the potential benefit and toxicity of (a) arsenic trioxide (ATO) as initial consolidation therapy and (b) maintenance therapy with oral tretinoin (ATRA) either alone or together with 6-mercaptopurine (MP) and methotrexate (MTX) in newly diagnosed patients with APL. All patients received induction therapy with ATRA, daunorubicin (DNR) and cytarabine. Adults (≥ 15 years) were randomized at study entry to receive a standard consolidation with 2 courses of ATRA plus DNR, or 2 courses of ATO as initial consolidation followed by 2 courses of ATRA plus DNR. Patients who remained in complete remission (CR; n=331) were then randomized (stratified by consolidation arm and age group) to one year of maintenance with ATRA alone (45 mg/m2/d) for 7 days repeated every other week (n=166) or in combination with MP 60 mg/m2/daily plus oral MTX 20 mg/m2/weekly (n=161). The target number of maintenance events was 146, and the study had 80% power to detect a hazard ratio of 1.6 at 5 years. We previously reported that the addition of ATO consolidation markedly improved event-free (EFS) and disease-free (DFS) survival (Blood 2010; 116:3751–3757). We now report the results of the maintenance randomization after a median follow up of 6.2 years. The two groups were well balanced by pretreatment characteristics. DFS, the primary endpoint, and overall survival (OS) were not statistically different for the two maintenance arms (log-rank p=0.14 and p=0.33, respectively). Evaluation by consolidation arm (by intention-to-treat, ITT) and by APL risk group also failed to demonstrate a significant advantage for either maintenance treatment. There was no interaction effect between consolidation and maintenance arms (p=0.78). Age, gender, CD56 expression and FLT3-ITD or TKD mutations at diagnosis did not have an impact on outcome by maintenance arm.ATRA*ATRA/MP/MTX*PDFS: overall41/16630/1610.14DFS by consolidation arm (ITT): ATO10/844/780.13no ATO31/8226/830.21DFS by risk group: low/intermediate25/12819/1300.20high16/3811/310.683-year DFS from CR79%87%0.056OS: overall22/16616/1650.33OS by consolidation arm (ITT): ATO8/843/810.15no ATO14/8213/840.72OS by risk group: low/intermediate14/1289/1340.20high8/387/310.733-year OS from study entry92%95%0.28*Number of events/number of patients in each group or subgroup. No treatment-related deaths were reported during maintenance therapy. Hematologic adverse events were more common in the combination arm (maximum grade 3/4, 18% vs 4%; p< 0.0001), as were non-hematologic adverse events (maximum grade 3/4, 36% vs 25%; p=0.033). Only 71 DFS events have occurred to date. Although the 3-yr DFS favors the combination arm, the differences in DFS and OS with the addition of MP and MTX to ATRA maintenance do not reach statistical significance. The addition of ATO consolidation therapy remains the most important determinant of DFS and OS for APL patients in first remission on this randomized trial. Among patients who were randomized to maintenance, only 5 patients who received ATO consolidation have relapsed – 2 from the combination arm and 3 from the ATRA alone arm. Relapse of APL is uncommon in patients who received ATO consolidation, and the need for any maintenance therapy in these patients has yet to be determined. Disclosures: Off Label Use: Arsenic trioxide as consolidation treatment for APL.

Neutropenia Is a Predictable and Early Event in Affected Patients with Relapsed/Refractory Multiple Myeloma Treated with Lenalidomide in Combination with Dexamethasone.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2879-2879 ◽  
Author(s):  
Sagar Lonial ◽  
Rachid Baz ◽  
Arlene S. Swern ◽  
Donna Weber ◽  
Meletios A. Dimopoulos
Keyword(s):  
Multiple Myeloma ◽  
Febrile Neutropenia ◽  
Adverse Events ◽  
Safety Profile ◽  
Research Funding ◽  
Phase Iii ◽  
Number Of Patients ◽  
Grade 3 ◽  
Over Time

Abstract Abstract 2879 Poster Board II-855 Background: Lenalidomide (len) is an immunomodulatory compound with established clinical efficacy and safety in patients with multiple myeloma (MM). Two pivotal phase III trials in patients with relapsed/refractory MM evaluating lenalidomide + dexamethasone (len + dex) vs placebo + dex (MM-009 and MM-010) demonstrated that len + dex is well tolerated with significant improvements in response and overall survival in comparison to placebo + dex (Weber et al, NEJM 2007; Dimopoulos et al, NEJM 2007). Despite a favorable safety profile, neutropenia is one of the most common hematologic adverse events in patients receiving len + dex. Patients who experience neutropenia may require dose adjustments or discontinuation of len + dex therapy. The aim of this study was to understand the incidence, onset, and duration of neutropenia in patients with relapsed/refractory MM receiving long-term administration of len + dex. Methods: Pooled data for patients treated with len + dex from the two phase III studies (MM-009/010) with a median follow-up of 48 months in all patients surviving as of the data cutoff of July 2008, were analyzed for all neutropenia reported as adverse events (neutropenic AE), including all related terms. The change in incidence and severity of neutropenic AE over time was determined by capturing the highest grade of event reported for each patient within each month. Both the severity (grades 1-4) and duration (days) of neutropenic AE were also determined for patients within each month. To evaluate the change in the rate of neutropenic AE for all patients by month, monthly rates were modeled using Poisson regression with a factor for month and the log of the total number of patients included as an offset parameter. Results: Of 353 patients treated with len + dex, 164 (46%) experienced a neutropenic AE of any grade at some point during the course of the study. A grade 3 or 4 event occurred in 137 (39%) patients. Of the patients who experienced neutropenic AE of any grade, 97 (59%) received G-CSF at some point in the study compared to 8 (4%) of the patients without neutropenic AE. Sixty percent of patients who experienced a neutropenic AE, experienced more than 1 event. Overall, neutropenic AE occurred early, with 52% and 76% of patients experiencing their most severe event within 6 and 12 months of therapy, respectively (Figure). Only 24% of patients who experienced neutropenia experienced their highest grade of event after 12 months of therapy. The median duration of neutropenic AE overall was 10 (25th percentile 8; 75th percentile 29) days. The majority of severe neutropenic AE were grade 3, with very few patients experiencing a grade 4 event. Of the 353 patients treated with len + dex, only 11 (3.1%) patients had febrile neutropenia (12 events). Seven of the patients had their first febrile neutropenia within the first 6 months and 4 patients after 12 months. Twelve patients (3.3%) had their study drug discontinued due to a neutropenic event. Overall, the incidence, severity, and the duration of any neutropenic events did not significantly change over time. Conclusions: Overall, the first neutropenic AE in patients receiving len + dex occurs early, with more than 50% of patients experiencing their highest grade of event within 6 months of initiation of therapy and only 3.1% of patients treated with len + dex developed febrile neutropenia. These data support the predictable safety profile of len + dex, thereby supporting the long-term use of len + dex in patients with relapsed/refractory MM, and demonstrating the predictable safety profile of this combination therapy. Disclosures: Lonial: Gloucester: Research Funding; Novartis: Consultancy; BMS: Consultancy; Millenium: Consultancy, Research Funding; Celgene: Consultancy. Baz:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Swern:Celgene: Employment. Weber:Celgene: Honoraria, Research Funding. Dimopoulos:Celgene: Honoraria.

scholarly journals Phase III Study of Adjuvant Ipilimumab (3 or 10 mg/kg) Versus High-Dose Interferon Alfa-2b for Resected High-Risk Melanoma: North American Intergroup E1609

2020 ◽  
Vol 38 (6) ◽  
pp. 567-575 ◽  
Author(s):  
Ahmad A. Tarhini ◽  
Sandra J. Lee ◽  
F. Stephen Hodi ◽  
Uma N. M. Rao ◽  
Gary I. Cohen ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Adverse Events ◽  
Statistical Significance ◽  
Interferon Alfa ◽  
Phase Iii ◽  
High Dose ◽  
7Th Edition ◽  
Grade 3 ◽  
Intent To Treat ◽  
High Dose Interferon

PURPOSE Phase III adjuvant trials have reported significant benefits in both relapse-free survival (RFS) and overall survival (OS) for high-dose interferon alfa (HDI) and ipilimumab at 10 mg/kg (ipi10). E1609 evaluated the safety and efficacy of ipilimumab at 3 mg/kg (ipi3) and ipi10 versus HDI. PATIENTS AND METHODS E1609 was a phase III trial in patients with resected cutaneous melanoma (American Joint Committee on Cancer 7th edition stage IIIB, IIIC, M1a, or M1b). It had 2 coprimary end points: OS and RFS. A 2-step hierarchic approach first evaluated ipi3 versus HDI followed by ipi10 versus HDI. RESULTS Between May 2011 and August 2014, 1,670 adult patients were centrally randomly assigned (1:1:1) to ipi3 (n = 523), HDI (n = 636), or ipi10 (n = 511). Treatment-related adverse events grade ≥ 3 occurred in 37% of patients receiving ipi3, 79% receiving HDI, and 58% receiving ipi10, with adverse events leading to treatment discontinuation in 35%, 20%, and 54%, respectively. Comparison of ipi3 versus HDI used an intent-to-treat analysis of concurrently randomly assigned patient cases (n = 1,051) and showed significant OS difference in favor of ipi3 (hazard ratio [HR], 0.78; 95.6% repeated CI, 0.61 to 0.99; P = .044; RFS: HR, 0.85; 99.4% CI, 0.66 to 1.09; P = .065). In the second step, for ipi10 versus HDI (n = 989), trends in favor of ipi10 did not achieve statistical significance. Salvage patterns after melanoma relapse showed significantly higher rates of ipilimumab and ipilimumab/anti–programmed death 1 use in the HDI arm versus ipi3 and ipi10 ( P ≤ .001). CONCLUSION Adjuvant therapy with ipi3 benefits survival versus HDI; for the first time to our knowledge in melanoma adjuvant therapy, E1609 has demonstrated a significant improvement in OS against an active control regimen. The currently approved adjuvant ipilimumab dose (ipi10) was more toxic and not superior in efficacy to HDI.

Immunochemotherapy with Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) Versus Fludarabine (F), Cyclophosphamide (C) and MabCampath (Cam) (FCCam) in Previously Untreated Patients (pts) with Advanced B-Chronic Lymphocytic Leukemia (B-CLL) : Experience On Safety and Efficacy within a Randomised Multicenter Phase III Trial of the french Cooperative Group On CLL and WM (FCGCLL/MW) and the “Groupe Ouest-Est d'Etudes Des Leucémies Aigües Et Autres Maladies Du sang” (GOELAMS) : CLL2007FMP (for fit medically patients).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 538-538 ◽  
Author(s):  
Stephane Lepretre ◽  
Therese Aurran ◽  
Beatrice Mahe ◽  
Bruno Cazin ◽  
Olivier Tournihlac ◽  
...  
Keyword(s):  
Adverse Events ◽  
Response Rate ◽  
B Cell Lymphoma ◽  
Response Rates ◽  
Safety Analysis ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Number Of Patients ◽  
Grade 3 ◽  
11Q Deletion

Abstract Abstract 538 Introduction: Recent data suggest that FCR immunochemotherapy improves response rates and Progression-Free Survival (PFS) of previously untreated CLL pts. The monoclonal antibody alemtuzumab, a humanized anti-CD52 antibody (Campath), has shown activity alone and in combination in CLL pts. In order to validate the place of Campath in combination with the synergic association FC, the FCGCLL/MW and the GOELAMS conducted a multicenter French and Belgian phase III trial, CLL2007FMP, to evaluate the efficacy and toxicity of FCCam versus FCR in previously untreated patients with advanced CLL. PFS was the primary-end-point of this trial. Methods and Patients: A cohort of 178 fit medically pts (cumulative illness rating scale (CIRS) score of up to 6), less than 65 years old, without 17p deletion, were enrolled between November 2007 and January 2009. Pts were randomly assigned to receive 6 oral courses of FC (F 40mg/m2 d1-3 and C 250 mg/m2 d1–3; q 28 days) in combination with either R (n=83; 375 mg/m2 i.v. d 0 at first cycle and 500 mg/m2 d1 all subsequent cycles; q 28 days) or Cam (n=82; 30 mg s/cut d1-3; q 28 days). Patients were stratified according to IgVH mutational status and 11q deletion. Anti-infective prophylaxis included trimethoprim-sulfamethoxazole and valaciclovir during immunochemotherapy and until the CD4-positive lymphocyte count reached 0,2 109/l. In the FCCAm arm, CMV monitoring was monthly performed by either PCR or antigenemia. The use of GSCF was recommended. The trial's recruitment was stopped in January 2009 after 165 pts had been randomized (83 and 82 respectively in the FCR and FCCam arms) because of an excess of mortality in the FCCam arm, while 13 patients were enrolled but not randomized because of this decision. Results: We reported here a preliminary analysis including baseline characteristics and response rates in the first 100 included pts but safety analysis of the whole cohort ; among the first 100 pts, 81% were Binet B, 19 % Binet C ; median age was 56.8 years (range 52.8 to 60.6). Percentages of pts with 11q deletion, unmutated IgVH status, and elevated β2m, were 18.5%, 48.4%, and 77.6%, respectively. A number of 76.5% (FCR arm) and 71.4% (FCCam arm) of pts received 6 cycles. Reasons for discontinuation were mainly related to persistent grade 3-4 neutropenia. Safety analysis data were availabel for 165 pts. Number of patients reported with Common Toxicity Criteria (CTC) grade 3-4 adverse events were observed in 87.8% (FCCam arm) versus 90.2% (FCR arm) (p = 0.76). Grade 3-4 neutropenia was the most frequently reported adverse event (79.6% with FCCam and 74.6% with FCR arm). Interestingly, percentage of observed grade 4 neutropenia was stable during FCR treatment (17.6% for cycle 1 and 17.9% for cycle 6) but increased during FCCam treatment (28.4% for cycle 1 and 45.5% for cycle 6). A total of 63 Serious Adverse events (SAE) were declared (19 with 18 pts in FCR arm, and 44 with 35 pts in FCCam arm) consisting mostly of the cases in febrile neutropenia (13 with FCR arm, 27 with FCCam arm); 7 patients died, all in the FCCam arm : 3 of B diffuse large B-cell lymphoma (one of them EBV positive), 1 of mucormycosis, 1 of septic shock due to P.aeruginosae and 2 of heart failure during neutropenia. The Overall Response Rate ( ORR) in the first 100 patients was 96% in the FCR arm compared to 85% in the FCCam arm (p=0.086). The Complete Response rate was 78% (FCR arm) versus 58% (FCCam arm) (p=0.072). PFS and OS are not yet evaluable. Conclusion: the FCCam regimen for the treatment of advanced CLL appeared to be associated with an unfavourable safety profile representing a significant limitation of its use in this indication. Other combinations with Alemtuzumab may be studied. Disclosures: No relevant conflicts of interest to declare.

Safety of Vinflunine in Patients with Advanced Urothelial Carcinoma Refractory to Platinum-based Chemotherapy: A Prospective Pilot Study

2019 ◽  
Vol 14 (1) ◽  
pp. 31-36
Author(s):  
Raafat Abdel-Malek ◽  
Kyrillus S. Shohdy ◽  
Noha Abbas ◽  
Mohamed Ismail ◽  
Emad Hamada ◽  
...  
Keyword(s):  
Pilot Study ◽  
Adverse Events ◽  
Urothelial Carcinoma ◽  
Transitional Cell ◽  
Chemotherapeutic Agents ◽  
Serious Adverse Events ◽  
Platinum Based Chemotherapy ◽  
Number Of Patients ◽  
Advanced Urothelial Carcinoma ◽  
Grade 3

Background: Several single chemotherapeutic agents have been evaluated as the second-line treatment of advanced urothelial carcinoma. Despite encouraging efficacy outcomes, toxicity has often led to dose modifications or discontinuation. We aimed to assess the safety of vinflunine in a particular population of advanced transitional cell carcinoma of urothelium (TCCU), that were exposed to the previous toxicity of chemotherapy. Methods: This is an open-label, prospective, single-center pilot study to evaluate the response rate and safety profile of vinflunine in patients with advanced TCCU. It was planned to enroll 25 evaluable patients. Eligible patients are those with progressive disease after first-line platinum-based regimen for advanced or metastatic disease. Results: The study was prematurely closed due to two sudden deaths that were judged by the review board as treatment-related. Only ten patients were evaluated and received at least one cycle of vinflunine. All but one were male and seven underwent radical surgery. Eight had a distant metastasis (mainly lung and/or liver). Disease control rate was 40%, four patients had a partial response with median duration of response of 3.5 months. The median overall survival was 3.2 months (95% CI:1.67- 4.73). There were three serious adverse events namely two sudden deaths and one grade 4 thrombocytopenia. Nine grade 3/4 adverse events occurred. The most common all-grade adverse events were fatigue (50%), constipation (40%) and vomiting (40%). Moreover, grade 3 fatigue occurred in 30% of patients. Only one patient, who achieved PR for 5 months, was fit to receive further cytotoxic chemotherapy. Conclusion: The activity of vinflunine in advanced urothelial carcinoma came at the expense of its safety. The use of vinflunine has to be limited to the selected group of patients. However, this is a single institute experience in a limited number of patients.

scholarly journals AB0381 THE UTILITY OF HYDROXYCHLOROQUINE (HCQ) THERAPY FOR TWO YEARS AS A SPARING CORTICOSTEROID AGENCY IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1490.3-1491
Author(s):  
K. Inoue ◽  
K. Misaki ◽  
N. Dobashi ◽  
M. Miyazaki ◽  
Y. Mako ◽  
...  
Keyword(s):  
Adverse Events ◽  
Maintenance Therapy ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Statistical Significance ◽  
Disease Activity Index ◽  
Patient Characteristics ◽  
Serum Complement ◽  
Wbc Count ◽  
Study Dose

Background:Prednisolone (PSL) and HCQ are key drugs in the therapy of SLE. However, since PSL induce many harmful adverse events, PSL is preferred to be reduced especially in the maintenance therapy. The efficacy of HCQ for reducing the dose of PSL has not been revealed yet. So, we focused on the cessation of PSL under the treatment of HCQ with conventional SLE therapy.Objectives:The aim of this study is to evaluate the efficacy and the safety of HCQ as co-treatment in the standard therapy of SLE.Methods:SLE patients (n=30) under the maintenance therapy were enrolled in this study. Dose of PSL, titer of anti-DNA antibody, WBC count, serum complement and SLE disease activity index (SLEDAI) were examined retrospectively at 0 and 12 months after administration of HCQ.Results:Baseline patient-characteristics are as follows (mean±S.E); the age of patients was 54.4±3.2 years old, 21 patients (70%) were female, the disease duration was 108.5±25.2 months, SLEDAI was 4.0±0.9, the dose of PSL was 10.3±1.7 mg/day, the titer of anti-DNA antibody was 7.3±1.8 IU/ml, C3 was 85±4.3 mg/dl and C4 was 18±1.6 mg/dl.The mean dose of PSL was reduced with statistically significance (pre-administration of HCQ:10.3±1.7 mg/day, 24 months after administration of HCQ:2.2±0.3 mg/day,p<0.0001). Furthermore, in this observation period, 6 patients could achieve the cessation of PSL.SLEDAI was also significantly reduced (4.0±0.9 vs 1.0±0.3,p<0.01).There was no statistical significance between before treatment by HCQ and after treatment in the titer of anti-DNA antibody (7.3±1.8 vs 2.8±1.6 IU/ml,p=0.06), WBC count (6208±4.9 vs 5096±3.3 /μl,p=0.06) and serum complement level (C3 85±4.3 mg/dl vs 89±4.0 mg/dl,p=0.52, C4 18±1.6 mg/dl vs 19±1.4 mg/dl,p=0.45). Relapse of SLE was clarified in only one patient.As for adverse events (AEs), Severe bacterial infection (n=4), herpes zoster (n=1) and patellar tendon rupture (n=1) were revealed. All cases of the AEs were fully recovered.Conclusion:Our study suggested that co-treatment with HCQ on standard SLE therapy could be enable to prevent the flare of SLE and reduce the dose of PSL with statistical significance. In some cases, we could achieve the cessation of PSL treatment.References:None.Disclosure of Interests:None declared

558 Programmed death (PD)-1 and PD-ligand-1 inhibitors in the treatment of non-small cell lung cancer: a systematic review of their efficacy and safety

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A592-A592
Author(s):  
Melissa Lingohr-Smith ◽  
Chelsea Deitelzweig ◽  
Grace Lin ◽  
Jay Lin
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Patient Outcomes ◽  
Nsclc Patient ◽  
Response Rates ◽  
Phase Iii ◽  
Combination Therapies ◽  
Phase Iii Clinical Trials ◽  
Programmed Death ◽  
Grade 3

BackgroundTreatment advances have been made in non-small cell lung cancer (NSCLC) with the development and approval of programmed death (PD)-1 and PD-ligand 1 (PD-L1) inhibitors. PD-1 and PD-L1 inhibitors may be used as monotherapies or in combination with other agents and have been shown to improve NSCLC patient outcomes in clinical trials. We conducted a systematic search to compare the efficacy and safety of PD-1/PD-L1 inhibitors in the treatment of NSCLC.MethodsA systematic literature search of PubMed was conducted to identify phase III clinical trials in which the efficacy of PD-1/PD-L1 inhibitors in the treatment of NSCLC was evaluated. PD-1 inhibitors included nivolumab and pembrolizumab; PD-L1 inhibitors included atezolizumab, avelumab, and durvalumab. Patient characteristics and efficacy data were extracted.ResultsSixteen phase III clinical trials were identified (nivolumab=4; pembrolizumab=5; atezolizumab=5; avelumab=1; durvalumab=1). Across the 3 nivolumab monotherapy trials (n=638; median ages: 61–63 years), median progression-free survival (PFS) ranged 2.3–4.2 months; response rates ranged 19%-26%; grade 3/4 adverse events occurred in 7%-18% of patients. Nivolumab in combination with iplimumab (n=583; median age: 64 years) had a median PFS of 5.1 months and response rate of 33%; grade 3/4 adverse events occurred in 33% of patients. Across the 3 pembrolizumab monotherapy trials (n=1,481; median ages: 63–64 years), median PFS ranged 3.9–10.3 months; response rates ranged 18%-45%; grade ≥3 adverse events occurred in 13%-27% of patients. In the 2 pembrolizumab combination therapy trials (n=688; median ages: 65 years), median PFS ranged 6.4–8.8 months; response rates ranged 48%-58%; grade ≥3 adverse events occurred in 67%-70% of patients. In the 4 atezolizumab combination therapy trials (n=1,486; median ages: 63–64 years), median PFS ranged 6.3–8.3 months; response rates ranged 47%-63.5%; grade 3/4 adverse events occurred in 54%-73% of patients. In the 3 monotherapy trials of atezolizumab (n=613; median age: 63 years), avelumab (n=396; median age: 64 years), and durvalumab (n=476; median age: 64 years), the median months of PFS were 2.7, 2.8, and 17.2, respectively; response rates were 14%, 15%, and 30%, respectively; grade ≥3 adverse events occurred in 15%, 10%, and 30.5% of patients, respectively.ConclusionsAlthough treatment responses varied, most of the evaluated PD-1/PD-L1 inhibitors were associated with a clinical benefit for NSCLC trial patients. Generally, treatment efficacy was greater with combination therapies, but adverse events occurred more frequently. Innovations in the targeting/personalization of PD-1/PD-L1 combination therapies will likely lead to improved NSCLC patient outcomes and further research is needed in this regard.

PS02.125: NEOADJUVANT CHEMOTHERAPY PLUS SURGERY FOR NON-T4 CSTAGE II/III ESOPHAGEAL CANCER: A SINGLE INSTITUTION EXPERIENCE IN JAPAN

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 156-157
Author(s):  
Masahiko Ikebe ◽  
Mitsuhiko Ohta ◽  
Masahiko Sugiyama ◽  
Masaru Morita ◽  
Yasushi Toh
Keyword(s):  
Esophageal Cancer ◽  
Postoperative Complications ◽  
Neoadjuvant Chemotherapy ◽  
Adverse Events ◽  
Standard Treatment ◽  
Conflicts Of Interest ◽  
Radical Surgery ◽  
Hospital Death ◽  
Number Of Patients ◽  
Grade 3

Abstract Background In Japan, following the results of JCOG 9907 trial, neoadjuvant chemotherapy (NAC) and radical surgery has been a standard treatment for Non-T4 cStage II/III esophageal cancer. Since 2009 we have also positioned NAC as standard treatment. We examined treatment outcomes and problems in our institute. Methods From 2009 to 2015, there were 64 patients with non-T4 stage II/III esophageal cancer treated with chemotherapy who are planned to undergo curative surgery. The standard NAC regimen consists of 2 courses of CDDP/5-FU (CF) therapy. As standard surgical procedure, subtotal esophagectomy, cervical anastomosis, three regional lymph node dissection were performed. Results The number of patients was 23/41 cases of cStage II/III respectively. 53 patients (88%) completed two courses of NAC. At the end of first course, NAC was terminated due to adverse events in 4 cases and due to the increasing tendency of tumors in 7 cases. NAC-induced adverse events of grade 3 or higher consists of myelosuppression in 27 cases (42%), appetite loss in 5 cases and so on. Surgery was performed in 61 cases (95%), of which R0 operation in 56 cases (88%), R1 operation in 3 cases and R2 operation in 2 cases. Three patients did not undergo surgery due to progressive disease. There were 7 cases (11%) of postoperative complications of Grade 3 or higher, but there was no in-hospital death. In the histological therapeutic effect, there were 5/41/7/4/3 cases for Grade 0/1a/1b/2/3, respectively. Three-year and five-year overall survival rate of all 64 patients were 68% and 47%. In 56 patients who underwent R0 surgery, they were 76% and 61% respectively. Conclusion From the viewpoint of adverse events and postoperative complications, NAC plus radical surgery for cStage II/III esophageal cancer could be performed safely. Considering that more than 60% of the patients belong to cStage III, this treatment strategy resulted in relatively favorable prognosis. Disclosure All authors have declared no conflicts of interest.

Postremission Therapy in Adult Acute Myeloid Leukemia (AML): A Randomized Comparison of Intensified Consolidation Therapy without Maintenance Therapy Against Conventional Consolidation with Maintenance Therapy -JALSG AML-97 Trial-.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 868-868 ◽  
Author(s):  
Shuichi Miyawaki ◽  
Hisashi Sakamaki ◽  
Shigeki Ohtake ◽  
Fumiharu Yagasaki ◽  
Kinuko Mitani ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Induction Therapy ◽  
Risk Group ◽  
Randomized Study ◽  
Risk Groups ◽  
Consolidation Therapy ◽  
Poor Risk ◽  
Short Course ◽  
To Receive ◽  
Good Risk

Abstract Between 1997 and 2001, JALSG conducted a randomized study to assess the optimal post remission therapy for adult AML in the first CR. The JALSG AML97 enrolled 809 previously untreated AML patients (pts) aged 15–64 yrs. Induction therapy consisted of cytarabine (100mg/m2 day1–7) and idarubicin (IDR 12mg/m2 day1– 3). If the patients did not achieve remission after the first induction therapy, the same therapy was given once more. Pts were categorized into good, intermediate or poor risk groups by risk factors based on the previous JALSG AML studies. All CR pts were randomized to receive either the intensified short course post remission regimen (arm A) or the conventional JALSG’s post remission regimen for AML including maintenance therapy (arm B). Arm A: 1) AraC 200mg/m2 day1–5+ Mitoxantrone (MTZ) 7mg/m2 day1–3, 2) AraC 200mg/m2 day1–5+Daunorubicin (DNR) 50mg/m2 day1–3, 3) AraC 200mg/ m2 day1–5+ Aclacinomycin (ACR) 20mg/m2 day1–5, 4) AraC 200mg/m2 day1–5+ Etoposide (ETP) 100mg/m2 day1–5 + Vincristine (VCR) 0.8mg/m2 day 8 + Vindesine (VDS) 2 mg/m2 day10. Arm B: 1) AraC 200mg/m2 day1–5 + MTZ 7mg/m2 day1–3, 2) Behenoyl AraC (BHAC) 200mg/m2 day1–7 + ETP 100mg/m2 day1–5 + DNR 50mg/m2 day1–3 + 6 mercptopurine (6MP) day1–7, 3) BHAC 200mg/m2 day1–7 + ACR 14mg/m2 day1–7, and then 6 courses maintenance therapy: 1) BHAC 170mg/m2 day1–5 + DNR 50mg/m2 day1,4+6MP day1–7, 2) BHAC 170mg/m2 day1–5 + MTZ 5mg/m2 day1–3, 3) BHAC 170mg/m2day1–5 + ETP 80mg/m2 day1,5,7 + VDS 2mg/m2 day1,8, 4) BHAC 170mg/m2 day1–5 + ACR 14mg/m2 day1–4 + 6MP day1–7, 5) BHAC 170mg/m2 day1–5 + DNR 50mg/m2 day1–4 + 6MP day1–7, 6) BHAC 170mg/m2 day1–5 + ETP 80mg/m2 day1,5,7 + VDS 2mg/m2 day1,8. Result: Of the 809 pts registered, 789 pts (median age: 45 years) were evaluable. 621 pts (78.7%) achieved CR after one or two courses of induction therapy. The 5-year OS rate of arm A was 45.6% and of arm B 53.2% (p=0.3259). The 5-year DFS rate of CR patients was 34.8% in arm A and 28.9% in arm B (p=0.4978). Among the good risk group, the 5-year OS rate of arm A was 62.1% and of arm B 70.2% (p=0.5068), and the 5-year DFS rate of arm A was 53.4% and of arm B 42.0% (p=0.3719). Among the intermediate risk group, the 5-year OS rate of arm A was 35.6% and of arm B 45.5% (p=0.4776), and the 5-year DFS rate of arm A was 26.0% and of arm B 26.1% (p=0.9653). Among the poor risk group, the 5-year OS rate of arm A was 29.7% and of arm B was 33.4% (p=0.6523), and the 5-year DFS rate of arm A was 20.4% and of arm B was 13.5% (p=0.6339). In conclusion: JALSG’s conventional post remission therapy consisting of 3 courses of consolidation and 6 courses of maintenance therapy could be replaced by a shorter duration of intensified consolidation therapy.

A Prospective, Randomized, Phase III Study of Melphalan 200 mg/m2 (MEL200) Versus Melphalan 100 mg/m2 (MEL100) in Newly Diagnosed Myeloma Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 55-55 ◽  
Author(s):  
Antonio Palumbo ◽  
Sara Bringhen ◽  
Maria Teresa Petrucci ◽  
Antonietta Falcone ◽  
Anna Marina Liberati ◽  
...  
Keyword(s):  
Stem Cell ◽  
Adverse Events ◽  
Response Rate ◽  
Complete Response Rate ◽  
Complete Response ◽  
Phase Iii ◽  
Psychiatric Disease ◽  
High Dose ◽  
Free Survival ◽  
Grade 3

Abstract Several trials have shown the superior impact of high-dose melphalan (usually 200 mg/m2, MEL200) versus standard therapy in myeloma patients. Intermediate-dose melphalan (100 mg/m2, MEL100) was also superior to the standard dose, but MEL100 has not been clinically compared with MEL200 in a randomized study. In a case-matched study, response rate and event-free survival of MEL200 were superior to MEL100, but overall survival (OS) was similar. In this prospective, randomized, phase III trial, we compared the efficacy and toxicity of MEL200 and MEL100. Between January 2002 and July 2006, 299 patients were enrolled. Inclusion criteria were previously untreated myeloma, aged < 65 and Durie and Salmon stage II or III. Exclusion criteria were abnormal cardiac function, respiratory disease, abnormal liver function, abnormal renal function, HBV, HCV, or HIV positivity, concomitant cancer or psychiatric disease. The institutional review board approved the protocol and written informed consent was obtained from all patients. All patients received: 2 dexamethasone-doxorubicin-vincristine debulking courses (doxorubicin 50 mg/m2 day 1, vincristine 1 mg day 1, dexamethasone 40 mg days 1, 2, 3, 4, each course repeated every 28 days), 2 cycles of cyclophosphamide (4 g/m2, day 1) plus G-CSF followed by stem cell harvest. The MEL200 group was conditioned with 2 cycles of melphalan 200 mg/m2 followed by stem cell reinfusion; the MEL100 group was conditioned with 2 courses of melphalan 100 mg/m2 followed by stem cell reinfusion. At the present, 246 patients, median age 57 (range 32–65), completed the assigned therapy and were evaluated for response, progression-free survival (PFS) and OS. One-hundred and twenty-four patients were randomized to MEL200 and 122 to MEL100. Patient characteristics were similar in both groups. Abnormal cytogenetics (13q deletion, t(4;14), t(11;14), p53) were 75% in MEL200 patients and 56% in MEL100 patients (p=0.05). Forty-six patients did not complete tandem MEL200; 36 patients did not complete tandem MEL100. The near complete response rate of MEL200 was superior to MEL100 (32% versus 18%, p=0.011), but partial response was 80% versus 71%, respectively (p=0.079). The median follow-up for censored patients was 26.5 months. The 3 years PFS was 51% in the MEL200 arm and 33% in the MEL100 arm (HR=0.81, 95% CI 0.55–1.21, p=0.31). The 3 years OS was 86% in the MEL200 group and 71% in the MEL100 group (HR=0.82, 95 CI 0.45–1.48, p=0.51). Duration of grade 4 neutropenia and thrombocytopenia was comparable in two arms, but MEL200 patients required more platelet transfusions (p=0.03). Grade 3–4 non-hematological adverse events were reported in 49% of the MEL200 patients and in 38% of the MEL100 patients (P=0.07). The most frequent grade 3–4 adverse events were infections (54% of MEL200 patients versus 45% of MEL100 patients, p=0.25), mucositis (31% of MEL200 patients versus 7% of MEL100 patients, p=0.002) and gastrointestinal toxicities (20% of MEL200 patients versus 14% of MEL100 patients, p=0.3). In conclusion, MEL200 resulted in a significantly higher near complete response rate but this did not translate in a superior PFS and OS.

Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab In Patients with Relapsed Follicular, Indolent and Mantle Cell Lymphomas – Final Results of the Randomized Phase III Study NHL 2–2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 856-856 ◽  
Author(s):  
Mathias J Rummel ◽  
Ulrich Kaiser ◽  
Christina Balser ◽  
Martina Beate Stauch ◽  
Wolfram Brugger ◽  
...  
Keyword(s):  
Overall Survival ◽  
Maintenance Therapy ◽  
Conflicts Of Interest ◽  
International Prognostic Index ◽  
Phase Iii ◽  
Rituximab Maintenance ◽  
Mantle Cell ◽  
Phase Iii Study ◽  
Grade 3 ◽  
Indolent Lymphomas

Abstract Abstract 856 Introduction: Promising results have been observed in two phase II studies evaluating the combination of bendamustine plus rituximab (B-R) in patients (pts) with relapsed/refractory follicular, other indolent or mantle cell lymphomas (MCL) (Rummel et al. JCO 2005; Robinson et al. JCO 2008). Fludarabine plus rituximab (F-R) is an established treatment option in this setting. Therefore, we initiated in 2003 a multicenter, randomized phase III study to compare the efficacy and safety of B-R versus F-R for pts with relapsed follicular (FL), indolent or MCL. Patients and methods: 219 pts with relapsed FL, indolent or MCL in need of treatment were randomized to rituximab 375 mg/m2 (day 1) plus either bendamustine 90 mg/m2 (days 1+2) or fludarabine 25 mg/m2 (days 1–3) q 28 days for a maximum of 6 cycles. Prophylactic use of antibiotics or granulocyte-colony stimulating factor (G-CSF) was not generally recommended; however in cases of severe granulocytopenia, G-CSF use was permitted. The primary endpoint was progression-free survival (PFS). The protocol was amended in 2006 to allow rituximab maintenance therapy (rituximab 375 mg/m2 q 3 months for up to 2 years) in both arms, following regulatory approvals in this setting. Results: 11 pts were not evaluable due to protocol violations, and were not followed further. A total of 208 pts were evaluable for the final analysis (109 B-R; 99 F-R). There were no significant differences between arms for patient characteristics, including age, stage, LDH, International Prognostic Index (IPI), follicular IPI (FLIPI), bone marrow infiltration and extranodal involvement. Most pts had stage IV (71.6% B-R; 60.6% F-R) or stage III disease (21.1% B-R and 25.3% F-R, respectively). Median patient age was 68 yrs (range 38–87). Patients had received a median of 1 prior therapy (range 1–7). Histological subtypes were distributed equally between the B-R and F-R arms: follicular 45.9 % and 47.5%, respectively; immunocytoma 11.9% and 11.1%; MCL 20.2% and 21.2%; other indolent lymphomas 23% and 20.2%. A median number of 6 cycles were given in both treatment arms, with 75.2% of B-R pts and 53.4% of F-R pts receiving 6 cycles, respectively. At the time of this analysis (June 2010), the median observation time was 33 months. Median PFS was significantly prolonged with B-R compared with F-R (30 vs 11 months; hazard ratio [HR] 0.51, 95 % confidence interval [CI] 0.34–0.67; p<0.0001). The overall response rate was significantly higher with B-R than with F-R (83.5 vs 52.5%, respectively; p< 0.0001). The CR rate with B-R was also significantly higher than that with F-R (38.5 vs 16.2%; p=0.0004). Overall survival did not differ significantly between arms, with 42 and 46 deaths documented in the B-R and F-R arms, respectively. There were no significant differences in the rates of alopecia, stomatitis, erythema, allergic reactions, peripheral neuropathy or infectious episodes between groups. Hematologic toxicities were also similar between arms: 8.9% grade 3/4 neutropenia with B-R vs 9.1% with F-R; 11.8% grade 3/4 leukocytopenia with B-R vs 12.4% with F-R. The overall incidence of serious adverse events was similar for the B-R and F-R groups (17.4 and 22.2%, respectively). An unplanned subanalysis showed that rituximab maintenance therapy significantly prolonged overall survival (HR 0.21, 95% CI 0.22–0.67; p=0.0008) and PFS (HR 0.27, 95% CI 0.27–0.59; p< 0.0001) in the small group of 40 pts who received this treatment (23 B-R, 17 F-R), compared with those who did not. Although the numbers are too small in this non-randomized comparison to draw some validated conclusions, these results appear to confirm the favorable role of rituximab maintenance. Conclusions: These data confirm the efficacy of B-R in pts with relapsed FL, indolent or MCL, and, in this setting, demonstrate a superior PFS benefit for this regimen in comparison with F-R. Disclosures: No relevant conflicts of interest to declare.

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