Docetaxel (T) given concurrently with or sequentially to anthracycline-based (A) adjuvant therapy (adjRx) for patients (pts) with node-positive (N+) breast cancer (BrCa), in comparison with non-T adjRx: First results of the BIG 2–98 Trial at 5 years median follow-up (MFU)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. LBA519-LBA519 ◽  
Author(s):  
J. P. Crown ◽  
P. Francis ◽  
A. Di Leo ◽  
M. Buyse ◽  
A. Balil ◽  
...  
Keyword(s):  
Final Analysis ◽  
Testing Procedure ◽  
Event Free Survival ◽  
Free Survival ◽  
Significance Level ◽  
First Results ◽  
Grade 3 ◽  
Mandated Evaluation ◽  
Overall Survival Analysis

LBA519 Background: The activity of T in metastatic BrCa mandated evaluation as adjRx. We compared the efficacy of T with, or after A, both followed by CMF (cyclophosphamide/ methotrexate/ 5-fluorouracil), versus non-T adjRx. Methods: Random assignment trial in resected N+ pts, 18–70 yrs, stratified by: center, 1–3 vs >3 nodes and age <50 vs ≥50. The treatment arms were (mg/m2, intravenously unless otherwise stated): Ia: A 75 q 3 weeks × 4 ⋄ CMF ×3 (oral C 100 day 1–14, F 600 + M 40 d 1+8; q 28 days). Arm Ib; AC 60/600 × 4⋄CMF × 3. Arm II: A75 × 3 ⋄T100 ×3 ⋄CMF ×3. Arm III: AT 50/75 ×4 ⋄ CMF × 3. Pts subsequently received hormono-(receptor+), and radiotherapy per local guidelines. Randomization was in the ratio (1:1:2:2). The trial was designed to have 80% power to detect a 78% hazard ratio (HR) for relapse in II+III v I, with final analysis at 1215, and interim at 405 and 810 events. The primary comparison between the II+III and I would be done at a one-tailed significance level of 0.025. Secondary comparisons of II vs Ia and III vs Ib would be done using a closed testing procedure at a one-tailed significance level of 0.025. The 95% confidence limits of the HR of III v II would be calculated. Due to a low relapse rate, the plan was amended with main analysis after 810 events or 5 years MFU. Results: 2887 pts were enrolled (6/1998–6/2001). Characteristics were well-balanced, 46% had >3N+. Grade 3/4 toxicity occurred in 22.9, 24.7, 35.3 and 28.6 % of pts in Ia, Ib, II and III respectively. At 62.2 months MFU (3/2006), 732 pts (25%) had events. Planned event-free survival (EFS) comparisons were: Conclusion: In this study, the HR for T v non-T adjRx was of borderline significance. There were possibly important differences related to schedule, sequential but not concurrent appearing superior to non-T adjRx. Overall survival analysis will require longer follow-up. Translational studies are underway. [Table: see text] [Table: see text]

Long-term follow-up of previously untreated patients (pts) with chronic lymphocytic leukemia (CLL) treated with ofatumumab (OFA) and chlorambucil (CHL): Final analysis of the phase 3 COMPLEMENT 1 trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7528-7528
Author(s):  
Fritz Offner ◽  
Tadeusz Robak ◽  
Ann Janssens ◽  
Govind Babu Kanakasetty ◽  
Janusz Kloczko ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Final Analysis ◽  
Lymphocytic Leukemia ◽  
Primary Analysis ◽  
Free Survival ◽  
Anti Cancer ◽  
Long Term Follow Up ◽  
Grade 3

7528 Background: Previously in the COMPLEMENT 1 study, treatment with OFA and CHL in pts with untreated CLL had shown a significant improvement in the progression-free survival (PFS) compared with CHL alone, and was well tolerated. Here, we report the final overall survival (OS) analysis of the 5-year (y) follow-up, updated investigator-assessed PFS and safety from the study. Methods: Untreated pts, not fit for fludarabine-based therapy (due to advanced age or co-morbidities) were randomized 1:1 to OFA+CHL or CHL alone. Pts in OFA+CHL arm received OFA (Cycle 1: 300 mg day (d) 1, 1000 mg d8; subsequent cycles: 1000 mg d1) in addition to CHL (10 mg/m2, d1-7) for 3 to 12 cycles of 28 d each. Pts in CHL arm received CHL only. Results: Overall, 447 pts were randomized to OFA+CHL (n = 221) or CHL (n = 226); 168 (76%) and 164 (73%) pts completed the scheduled treatments, respectively. Baseline characteristics were similar in both arms. The investigator-assessed median PFS was 23.4 months (mos) in the OFA+CHL arm and 14.7 mos in the CHL arm (HR: 0.61 [95% CI 0.49, 0.76], p < 0.001). Median OS could not be estimated for the OFA+CHL arm and was 84.7 mos for the CHL arm (HR: 0.88 [95% CI 0.65, 1.17], p = 0.363). Estimated OS rate (95% CI) at 5 y was 68.5% (61.5%, 74.5%) in the OFA+CHL arm, and 65.7% (58.6%, 71.9%) in the CHL arm. Post-treatment anti-cancer therapy after discontinuation was received by a greater proportion of pts in the CHL (66%) vs. OFA+CHL (56%), and started earlier in the CHL arm (486 d) vs. OFA+CHL (743 d) arm. Overall, 84 (39%) pts in the OFA+CHL, and 99 (44%) pts in the CHL arms died during the study with 5 on-treatment deaths in each group. Grade ≥3 adverse events were seen in 64% and 48% of pts in the OFA+CHL vs. CHL arms, respectively, most common being (≥5% in either arm) neutropenia (26% vs. 15%), thrombocytopenia (5% vs. 10%), pneumonia (9% vs. 5%), and anemia (5% vs. 5%). Conclusions: This 5-y survival follow-up analysis supported the results from primary analysis with an estimated 12% (not significant) and 39% risk reduction in OS and PFS, respectively, in the OFA+CHL arm compared with the CHL arm. No new safety concerns were observed in the OFA+CHL arm. Clinical trial information: NCT00748189.

Maintenance low-dose chemotherapy in patients with high-risk (HR) rhabdomyosarcoma (RMS): A report from the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG).

2018 ◽  
Vol 36 (18_suppl) ◽  
pp. LBA2-LBA2 ◽  
Author(s):  
Gianni Bisogno ◽  
Gian Luca De Salvo ◽  
Christophe Bergeron ◽  
Meriel Jenney ◽  
Johannes H.M. Merks ◽  
...  
Keyword(s):  
Complete Remission ◽  
Metronomic Chemotherapy ◽  
Relative Reduction ◽  
Free Survival ◽  
Significance Level ◽  
Group Iii ◽  
Power Testing ◽  
Grade 3 ◽  
Low Dose Chemotherapy

LBA2 Background: Most patients with localized RMS achieve complete remission during standard (std) treatment but approximately 20-30% of them relapse and chance of salvage is poor. We tested whether adding maintenance metronomic chemotherapy after std chemotherapy would improve survival for patients with non metastatic RMS defined as HR according to EpSSG stratification. Methods: Patients (pts) age >6 months <21 years, with N0 alveolar (A)RMS or incompletely resected (Group II or III) embryonal (E)RMS arising in an unfavorable primary site and/or N1 in complete remission after std treatment including 9 cycles of ifosfamide, vincristine and actinomycin D +/- doxorubicin, surgery and/or radiotherapy were eligible for randomization to stop treatment (Std-arm) or receive maintenance chemotherapy (M-arm) with 6 28-day cycles of iv vinorelbine 25 mg/m2 on day 1,8,15 of each cycle and continuous daily oral cyclophosphamide 25 mg/m2 . The study was initially designed with 80% power (5% 2-sided alpha level) to detect an increase in 3 yr Event Free Survival (EFS) from 55% to 67%, a Hazard Ratio of 0.67, but was successively amended to allow a detection of a relative reduction in the relapse rate of 50% in the M-arm, with 80% power, testing at the 5% significance level (2-sided). Results: 670 pts were entered between 4/2006-12/2016, with 371 confirmed eligible and 186 assigned to the std-arm and 185 to M-arm. Clinical features were well balanced in the two arms and included ERMS 67%, ARMS 33%, age 10+ years 21%; IRS Group III 86%; N1 16%. Most common primary tumor sites were parameningeal (32%) and “other” sites (23%). With median follow up of 5 years in surviving pts, 3 yr EFS and overall survival (OS) in M-arm vs Std-arm were respectively: EFS 78.4% (95% IC -71.5-83.8) vs 72.3% (95% IC -65.0-78.3) (p 0.061) and OS 87.3% (95% IC 81.2-91.6) vs 77.4 (95% IC 70.1-83.1) (p = 0.011). Toxicity in the M-arm was manageable: grade 3/4 febrile neutropenia in 25% of pts, grade 4 neurotoxicity in 1.1%. Conclusions: The addition of maintenance after std treatment significantly improves OS in HR RMS patients and support its inclusion in future EpSSG trials. Clinical trial information: 2005-000217-35.

scholarly journals Survival analysis of afatinib versus erlotinib for individuals with advanced del19 lung adenocarcinoma with asymptomatic brain metastasis after pemetrexed-cisplatin chemotherapy: a retrospective study

2020 ◽  
Vol 48 (8) ◽  
pp. 030006052093709
Author(s):  
Ye Jiang ◽  
Wenli Chen ◽  
Weiguang Yu ◽  
Ning Shi ◽  
Guowei Han ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Lung Adenocarcinoma ◽  
Primary Outcome ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Secondary Outcomes ◽  
Grade 3

Objective To evaluate survival following afatinib (AF) and erlotinib (ER) treatment in advanced del19 lung adenocarcinoma (AD19LA) with asymptomatic brain metastasis (ABM) after pemetrexed–cisplatin chemotherapy (PCC). Methods Data were retrospectively analysed from individuals with AD19LA and ABM after PCC who received AF or ER for 2 years or until intolerable adverse events (AEs), withdrawal, or death. The primary outcome was survival; secondary outcomes were AEs. Results The final analysis included 174 AD19LA individuals (AF: n = 86; ER: n = 88) with a median follow-up of 24.2 months (IQR 2.1–28.3). Significant differences in overall survival (16.2 months [95%CI 15.4–17.1] for AF vs 7.2 months [95%CI 6.3–8.1] for ER) (HR 0.50, 95%CI 0.36–0.71, p<0.0001) and median progression-free survival (9.4 months [95%CI 8.5–9.7] for AF vs 5.6 months [4.7–6.2] for ER) (HR 0.66, 95%CI 0.47–0.94, p=0.02) were observed between the groups. Rates of all-grade AEs were 82.5% for AF and 72.7% for ER, and rates of grade ≥3 AEs were 37.2% for AF and 34.0% for ER. Conclusion Compared with ER, AF treatment may be more beneficial in terms of survival in the management of AD19LA after PCC with a tolerable safety profile.

Busulphan-melphalan as a myeloablative therapy (MAT) for high-risk neuroblastoma: Results from the HR-NBL1/SIOPEN trial.

2011 ◽  
Vol 29 (18_suppl) ◽  
pp. 2-2 ◽  
Author(s):  
R. L. Ladenstein ◽  
U. Poetschger ◽  
R. Luksch ◽  
P. Brock ◽  
V. Castel ◽  
...  
Keyword(s):  
High Risk ◽  
Mycn Amplification ◽  
Severe Toxicity ◽  
Event Free Survival ◽  
Eligibility Criteria ◽  
Free Survival ◽  
Stage 4 ◽  
Significant Difference ◽  
Grade 3

2 Background: The HR-NBL1 trial of the European SIOP Neuroblastoma Group randomised 2 MAT regimens with the primary aim to demonstrate superiority based on event free survival (EFS). Methods: At randomisation closure, 1,577 high-risk neuroblastoma patients (944 males) had been included since 2002; with INSS stage 4 disease (1,369 pts) > 1 year, infants (65 pts) and stage II and III (143 pts) of any age with MYCN amplification. Response eligibility criteria prior to randomisation after Rapid COJEC Induction (J Clin Oncol, 2010) ± 2 courses of TVD (Cancer, 2003) included complete bone marrow remission and ≤ 3, but improved, mIBG positive spots. The MAT regimens were BuMel (oral busulfan till 2006, 4x150mg/m2 in 4 equal doses, or after 2006 intravenous use according to body weight and melphalan 140mg/m2/day) and CEM (carboplatin ctn. infusion [4xAUC 4.1mg/ml.min/day], etoposide ctn. infusion [4x338mg/m2day or 4x200mg/m2/day*], melphalan [3x70mg/m2/day or 3x60mg/m2/day*. *reduced if GFR<100ml/min/1.73m2]). A minimum of 3x10E6 CD34/kgBW PBSC were requested. VOD prophylaxis included ursadiol, but not prophylactic defibrotide. Local control included surgery and radiotherapy of 21 Gy. A total of 598 patients were randomised (296 BuMel, 302 CEM). The median age at randomisation was 3 years (1-17.2) with a median follow up of 3 years. Results: At the last analysis, the Peto rule of p<0.001 was met. A significant difference in EFS in favour of BuMel (3-years EFS 49% vs 33%) was observed as well as for overall survival (3-years OS 60% vs 48%, p=0.004). This difference was mainly related to the relapse and progression incidence, which was significantly (p<0.001) lower with BuMel (48% vs 60%). The severe toxicity rate up to day 100 (ICU and toxic deaths) was below 10%, but was significantly higher for CEM (p=0.014). The acute toxic death rate was 3% for BuMel and 5% for CEM (NS). The acute MAT toxicity profile favours the BuMel regimen in spite of a total VOD incidence of 18% (grade 3:5%). Based on these results and following advice from the DMC, the randomisation was closed early. Conclusions: BuMel was demonstrated to be superior to CEM and hence is recommended as standard treatment.

scholarly journals Ofatumumab maintenance prolongs progression-free survival in relapsed chronic lymphocytic leukemia: final analysis of the PROLONG study

2019 ◽  
Vol 9 (12) ◽  
Author(s):  
Marinus van Oers ◽  
Lukas Smolej ◽  
Mario Petrini ◽  
Fritz Offner ◽  
Sebastian Grosicki ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Lymphocytic Leukemia ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Third Line ◽  
Grade 3 ◽  
Third Line Treatment

AbstractWe report the final analysis of the PROLONG study on ofatumumab maintenance in relapsed chronic lymphocytic leukemia (CLL). In all, 480 patients with CLL in complete or partial remission after second- or third-line treatment were randomized 1:1 to ofatumumab (300 mg first week, followed by 1000 mg every 8 weeks for up to 2 years) or observation. Median follow-up duration was 40.9 months. Median progression-free survival was 34.2 and 16.9 months for ofatumumab and observation arms, respectively, (hazard ratio, 0.55 [95% confidence interval, 0.43–0.70]; P < 0.0001). Median time to next treatment for ofatumumab and observation arms, respectively, was 37.4 and 27.6 months (0.72 [0.57–0.91]; P = 0.0044). Overall survival was similar in both arms; median was not reached (0.99 [0.72–1.37]). Grade ≥ 3 adverse events occurred in 62% and 51% of patients in ofatumumab and observation arms, respectively, the most common being neutropenia (23% and 10%), pneumonia (13% and 12%) and febrile neutropenia (6% and 4%). Up to 60 days after the last treatment, four deaths were reported in the ofatumumab arm versus six in the observation arm, none considered related to ofatumumab. Ofatumumab maintenance significantly prolonged progression-free survival in patients with relapsed CLL and was well tolerated.

Final analysis of single-arm confirmatory study of definitive chemoradiotherapy including salvage treatment in patients with clinical stage II/III esophageal carcinoma: JCOG0909.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4545-4545
Author(s):  
Yoshinori Ito ◽  
HIROYA TAKEUCHI ◽  
Gakuto Ogawa ◽  
Ken Kato ◽  
Masakatsu Onozawa ◽  
...  
Keyword(s):  
Esophageal Carcinoma ◽  
Final Analysis ◽  
Salvage Treatment ◽  
Stage Ii ◽  
Combined Modality Treatment ◽  
Definitive Chemoradiotherapy ◽  
Free Survival ◽  
Operative Complications ◽  
Grade 3

4545 Background: Definitive chemoradiotherapy (dCRT) consisting of 5-fluorouracil (5-FU) and cisplatin (CDDP) with 60 Gy radiotherapy (RT) for clinical (c) Stage II/III esophageal carcinoma (EC) is a standard treatment for patients (pts) refusing surgery (S) in Japan based on the previous trial (JCOG9906). However, poor survival, high incidence of late toxicities, and severe complications of salvage S are problems. We conducted a single-arm confirmatory study of CRT modifications including salvage treatment (ST) to reduce CRT toxicities and facilitate ST to improve survival. We reported the 3-year survival at 2018 ASCO Annual Meeting. We report the final data after 5-year follow-up. Methods: EC pts with cStage II/III (UICC 6th, non-T4), PS 0-1, and age 20-75 years were eligible. Chemotherapy (CT) was CDDP (75 mg/m2 on days 1, 29) and 5-FU (1000 mg/m2/d on days 1-4, 29-32). RT was administered to a total dose of 50.4 Gy with elective nodal irradiation of 41.4 Gy. Good responders after dCRT received additional 1-2 cycles of CT. For residual or recurrent disease, salvage endoscopic resection (ER) or S was performed based on the prespecified criteria. Planned sample size was 95, with one-sided alpha of 5% and power of 80%, expected and threshold 3-year overall survival (OS) as 55% and 42%. Key secondary endpoint was ST related toxicity. Final analysis was planned after 5-year follow-up for all pts. Results: From 4/2010 to 8/2014, 96 pts were enrolled, two were ineligible and 94 were included in efficacy analysis (cStage IIA/IIB/III, 22/38/34). Complete response was achieved in 55 pts (59%). Salvage ER and S were performed in 5 (5%) and 27 pts (29%). R0 resection of salvage S was achieved in 23 (85%). With a median follow-up of 5.95 years, 3- and 5-year OS was 74.2% (90% CI 65.9-80.8%) and 64.5% (95% CI 53.9-73.3%). 5-year progression-free survival and esophagectomy-free survival were 48.3% (95% CI 37.9-58.0%) and 54.9% (95% CI 44.3-64.4%). 5-year OS after salvage S was 31.0% and hazard ratio of R1-2 to R0 was 5.635 (95% CI: 1.818-17.467). No complications occurred after salvage ER. Five pts (19%) showed ≥ grade 3 operative complications and 1 treatment related death due to bronchus-pulmonary artery fistula occurred after salvage S. Only 9 pts (9.6%) showed grade 3 late toxicities. And no late operative complications more than grade 3 were observed. Conclusions: This combined modality treatment of dCRT with ST showed acceptable toxicities, favorable 5-year survival, and promising esophageal preservation. Clinical trial information: jRCTs031180110 .

scholarly journals Modified 5-fluorouracil/leucovorin/irinotecan as a feasible and efficacious second-line chemotherapeutic regimen in advanced gastric cancers

2018 ◽  
Vol 07 (04) ◽  
pp. 219-222 ◽  
Author(s):  
Anant Ramaswamy ◽  
Vikas Ostwal ◽  
Kushal Gupta ◽  
Vijai Simha ◽  
Anup Toshniwal ◽  
...  
Keyword(s):  
Response Rate ◽  
Therapy Response ◽  
Second Line ◽  
Event Free Survival ◽  
Second Line Therapy ◽  
Chemotherapeutic Regimen ◽  
Free Survival ◽  
Common Grade ◽  
Grade 3

Abstract Background: Modified 5-fluorouracil/leucovorin/irinotecan (mFOLFIRI) is a commonly used combination second-line chemotherapeutic regimen in advanced gastric cancer (AGC). Materials and Methods: Patients diagnosed with AGC, receiving biweekly mFOLFIRI between July 2013 and June 2016, as second-line chemotherapy were retrospectively analyzed for tolerance, prognostic factors, event-free survival (EFS), and overall survival (OS). Results: Overall, 91 patients were administered a median of 6 cycles of therapy. Response rate was 29.7% and clinical benefit rate was 57.2%. With a median follow-up of 11.5 months, median EFS was 3.98 months (95% confidence interval [CI]: 2.54–5.41) and median OS was 7.73 months (95% CI: 5.30–10.15). Common Grade 3 and Grade 4 adverse events were neutropenia (18.7%), febrile neutropenia (9.9%), thrombocytopenia (7.7%), and vomiting (4.4%). Nearly 33% of patients required dose modification during therapy. Conclusions: mFOLFIRI regimen as a second-line therapy in AGCs appears feasible and efficacious in clinical practice.

Final Analysis of the Australasian Leukaemia and Lymphoma Group (ALLG) APML4 Trial: All-Trans Retinoic Acid (ATRA), Intravenous Arsenic Trioxide (ATO) and Idarubicin (IDA) As Initial Therapy for Acute Promyelocytic Leukemia (APL)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 375-375 ◽  
Author(s):  
Harry J Iland ◽  
Marnie Collins ◽  
Mark S Hertzberg ◽  
Michael Seldon ◽  
Andrew P Grigg ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Adverse Events ◽  
Arsenic Trioxide ◽  
Final Analysis ◽  
Risk Category ◽  
Cutaneous Toxicity ◽  
Free Survival ◽  
Increased Risk ◽  
Grade 3

Abstract BACKGROUND The combination of ATRA and anthracycline-based chemotherapy has traditionally been regarded as the gold standard for induction and consolidation in previously untreated APL patients (pts), with ATO usually reserved for relapse. Recent data in Sanz low-risk (LR) and intermediate-risk (IR) APL indicate ATRA + ATO is superior to ATRA + chemotherapy (N Engl J Med 2013), but the optimal therapy for high-risk (HiR) pts remains unclear. In an attempt to improve anti-leukemic efficacy whilst limiting reliance on anthracyclines for all risk categories of APL, the ALLG incorporated ATO into an ATRA + reduced chemotherapy backbone, and the results of an interim analysis with a median follow-up of 2 years (yr) have been published (Blood 120:1570, 2012). Herein, we report results of the protocol-specified final analysis, conducted when all surviving pts had been followed for at least 2 yr after completion of consolidation. METHODS As published, APML4 protocol treatment comprised: (i) induction with ATRA (45 mg/m2 d1-36), IDA (12 mg/m2 d2,4,6,8), ATO (0.15 mg/kg d9-36), prophylactic prednisone (1 mg/kg d1-10) and aggressive hemostatic support; (ii) consolidation with ATRA and ATO (continuous in cycle 1, intermittent in cycle 2); (iii) 2 yr oral maintenance with ATRA, 6-mercaptopurine and methotrexate. Between 2004-2009, 124 evaluable pts were accrued, and median follow-up by the censor-reversing Kaplan-Meier method in this final analysis is 4.2 yr. RESULTS Median age was 44 (3-78) yr, median white cell count was 2.4 x 109/L (0.1-85.8), and median platelet count 22 x 109/L (2-173). Risk groups were 33 LR, 67 IR, 23 HiR, 1 unknown. FLT3 mutations were present in 44%, and 11% had ≥ 2 additional cytogenetic abnormalities (2+ACA). There were 4 (3.2%) deaths during induction (myocardial infarction d1, cerebral hemorrhage d3 and d7, cerebral edema and seizures d30). Grade 3-4 non-hematological adverse events included differentiation syndrome in 14%, and frequent but reversible biochemical hepatic and gastrointestinal toxicity. Q-Tc prolongation > 500 msec occurred in 14%, but there were no cases of ventricular arrhythmias or torsades de pointe. Significant neurological and cutaneous toxicity were infrequent. After induction, 118 pts (95%) achieved hematological complete remission; 112 commenced consolidation, and all were in molecular remission after cycle 2. A total of 5 relapses and 3 deaths have occurred post-induction, but none of the deaths were attributable to protocol therapy. Severe adverse events were less common during the chemotherapy-free consolidation cycles, especially cycle 2. The frequency of grade 3-4 neutropenia was 62% in cycle 1 and 27% in cycle 2, but there was no grade 3-4 thrombocytopenia. The following table lists event-free survival (EFS), disease-free survival (DFS), overall survival (OS) and cumulative incidence of relapse (CIR): Table All pts LR IR HiR 2 yr 5 yr 2 yr 5 yr 2 yr 5 yr 2 yr 5 yr EFS 92% 90% 97% 97% 93% 89% 83% 83% DFS 97% 95% 100% 100% 97% 93% 95% 95% OS 94% 94% 97% 97% 96% 96% 87% 87% CIR 3% 5% 0% 0% 3% 7% 5% 5% In univariate analysis, 2+ACA predicted for inferior DFS (P = .04), whereas age > 70 was associated with increased risk of early death (ED, P = .02), inferior EFS (P = .0002), and inferior OS (P = .001). Neither Sanz risk category nor FLT3 mutation status was significantly correlated with these outcome endpoints (all P > .05). In multivariate analysis, the significant associations of 2+ACA (P = .04 for DFS) and age > 70 (P = .0002 for EFS, P = .005 for OS) were retained. In addition, Sanz risk category was correlated with EFS (P[trend] = .003) and OS (P[trend] = .02). When compared with our previous ALLG APML3 trial (ATRA + IDA for induction and consolidation without ATO; Haematologica 2012), treatment with APML4 was associated with substantial and statistically significant improvements (see Figure) in EFS (P = .002), DFS (P = .001) and OS (P = .02). The significance of trial assignment was retained in multivariate analysis when APML3 and APML4 data were combined. CONCLUSIONS APML4 is a potent anti-leukemic regimen with manageable toxicity and a low ED rate. EFS and OS remain impressive with mature follow-up, and were influenced primarily by advanced age and Sanz risk category. The CIR was 5%, and was only associated with 2+ACA. Our results support the inclusion of ATO in induction and consolidation as front-line therapy for APL whilst simultaneously limiting cumulative anthracycline exposure. Figure 1 Figure 1. Disclosures Off Label Use: Arsenic trioxide is currently only registered in the US, Europe and Australia for the treatment of relapsed APL. This report includes its use in the initial treatment of APL.

scholarly journals FAS and Subsequent Therapies in Pancreatic Neuroendocrine Tumors

2021 ◽  
Author(s):  
Jane E. Rogers ◽  
Michael Lam ◽  
Daniel M. Halperin ◽  
Cecile G. Dagohoy ◽  
James C. Yao ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Pancreatic Neuroendocrine Tumors ◽  
Free Survival ◽  
Prior Therapy ◽  
Well Differentiated ◽  
Grade 3 ◽  
Line Of Therapy

We evaluated outcomes of treatment with 5-fluorouracil (5-FU), doxorubicin, and streptozocin (FAS) in well-differentiated pancreatic neuroendocrine tumors (PanNETs) and its impact on subsequent therapy (everolimus or temozolomide). Advanced PanNET patients treated at our center from 1992 to 2013 were retrospectively reviewed. Patients received bolus 5-FU (400 mg/m2), streptozocin (400 mg/m2) (both IV, days 1-5) and doxorubicin (40 mg/m2 IV, day 1) every 28 days. Overall response rate (ORR) was assessed using RECIST version 1.1. Of 243 eligible patients, 220 were evaluable for ORR, progression-free survival (PFS), and toxicity. Most (90%) had metastatic, nonfunctional PanNETs; 14% had prior therapy. ORR to FAS was 41% (95% confidence interval [CI]: 36-48%). Median follow-up was 61 months. Median PFS was 20 (95% CI: 15-23) months; median overall survival (OS) was 63 (95% CI: 60-71) months. Cox regression analyses suggested improvement with first-line vs subsequent lines of FAS therapy. Main adverse events ≥ grade 3 were neutropenia (10%) and nausea/vomiting (5.5%). Dose reductions were required in 32% of patients. Post-FAS everolimus (n=108; 68% second line) had a median PFS of 10 (95% CI: 8-14) months. Post-FAS temozolomide (n=60; 53% > fourth line) had an ORR of 13% and median PFS of 5.2 (95% CI: 4-12) months. In this largest reported cohort of PanNETs treated with chemotherapy, FAS demonstrated activity without significant safety concerns. FAS did not appear to affect subsequent PFS with everolimus; this sequence is being evaluated prospectively. Responses were noted with subsequent temozolomide-based regimens although PFS was possibly limited by line of therapy.

scholarly journals MBCL-04. 5 – AZACYTIDINE IN TREATMENT OF CHILDREN WITH DE NOVO AND RELAPSED METASTATIC MEDULLOBLASTOMA: RESULTS OF INTERCENTER PILOT STUDY

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii387-iii387
Author(s):  
Andrey Levashov ◽  
Dmitry Khochenkov ◽  
Anna Stroganova ◽  
Marina Ryzhova ◽  
Sergey Gorelyshev ◽  
...  
Keyword(s):  
Gene Amplification ◽  
De Novo ◽  
Prognostic Significance ◽  
N Gene ◽  
Free Survival ◽  
Tumor Bed ◽  
Craniospinal Radiation ◽  
Therapeutic Program ◽  
Grade 3

Abstract The aim of this study was to estimate treatment toxicity and event-free survival (EFS) according to therapeutic program, MYC/MYC-N gene amplification and MGMT/DNMT (1, 3a, 3b) proteins expression in tumor cells. From 2016 to 2018 twenty four patients were included in trial. Children underwent adjuvant therapy: craniospinal radiation (CSI) or local radiation therapy (RT) to the relapsed site up to 23.4Gy with 5-azacytidine, 2 cycles methotrexate/5-azacytidine/cisplatin/etoposide, 3 cycles 5-azacytidine/temozolomide - for relapsed group (arm A, n = 5); for patients with de novo medulloblastoma: arm B, n = 11 – vincristine/cyclophosphamide/cisplatin/etoposide (OPEC) - based induction, CSI 36Gy + local RT to the tumor bed up to 54Gy with 5-azacytidine, 1 cycle OPEC and 2 cycles thiophosphamide/carboplatin with auto stem cell transplantation (auto-SCT); arm C, n = 8 – cyclophosphamide/cisplatin - based induction, CSI 23.4 Gy followed by 2 cycles 5-azacytidine/thiophosphamide/carboplatin with auto-SCT, local RT with 5-azacytidine. The combination of 5-azacytidine with local RT or temozolomide was safety and tolerability. Arm C was discontinued due to severe gastrointestinal grade 3/4 toxicity, hemorrhagic syndrome after combination of 5-azacytidine with thiophosphamide/carboplatin. EFS was 0% in arm A, 53.0 ± 15.5%, 50.0 ± 17.7% in arms B and C, a median follow-up 8.8 ± 1.1 months (arm A), 18.8 ± 2.5 months (arm B), 25.0 ± 4.4 months (arm C). Addition of 5-azacytidine to RT or chemotherapy did not improve EFS of patients with MYC/MYC-N gene amplification positive tumor. There was not determined any prognostic significance of MGMT/DNMT (1, 3a, 3b) proteins expression in this cohort.

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