Comparison of chemoradiotherapy (CRT) and chemotherapy (CT) in patients with a locally advanced pancreatic cancer (LAPC) controlled after 4 months of gemcitabine with or without erlotinib: Final results of the international phase III LAP 07 study.

2013 ◽  
Vol 31 (18_suppl) ◽  
pp. LBA4003-LBA4003 ◽  
Author(s):  
Pascal Hammel ◽  
Florence Huguet ◽  
Jean-Luc Van Laethem ◽  
David Goldstein ◽  
Bengt Glimelius ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Final Analysis ◽  
Primary Objective ◽  
Phase Iii ◽  
Progression Rate ◽  
Kaplan Meier ◽  
Lost To Follow Up

LBA4003 Background: CRT in patients with LAPC controlled after induction CT could be superior to continuing CT (Huguet, JCO 2007). The role of erlotinib is unknown. We aimed to define the role of 1) CRT after disease control with gemcitabine, 2) erlotinib in LAPC. Methods: LAPC PS 0-2 patients were first randomized to gemcitabine alone or plus erlotinib 100 mg/d for 4 months (R1, stratification: center, PS). Patients with controlled disease were then randomized to 2 additional months of CT (Arm 1) or CRT (Arm 2) 54 Gy and capecitabine 1600 mg/m2/d (R2, stratification: center, initial arm). Patients receiving erlotinib at R1 had maintenance with this drug after protocol completion. Quality control for radiotherapy included dummy runs and assessment of treated patients. Primary objective: overall survival (OS) in R2 patients. Secondary objectives: role of erlotinib on OS (R1), tolerance, predictive markers, and circulating tumor cells. Taking into account a 30% progression rate between R1 and R2, and 5% lost to follow-up, 722 patients were required to observe 392 deaths to show a median OS increase from 9 to 12 m (HR=0.75) in the CRT arm (2 sided α=5% and β=20%) with planned interim analyses using alpha spending function and O’Brien Fleming boundaries (to reject H0 or H1). Kaplan-Meier, log rank and univariate Cox tests were used. Results: From 442 pts included for R1, 269 pts reached R2 (arm1:136; arm 2:133). Main baseline characteristics in arms 1/2: female 44%/56%, mean age 63/62, head tumor 65%/62%, PS 0 56%/48%. After a median follow-up of 36 m, 221 deaths had occurred allowing the planned interim analysis (information fraction 56.4%). OS in R2 pts was 16.5 m [15.5-18.5] and 15.3 m [13.9–17.3] in arms 1 and 2, respectively (HR=1.03 [0.79-1.34], p=0.83). IDMC has confirmed that the futility boundary for the hypothesis of CRT superiority was crossed and considered this as the final analysis of the study. Conclusions: Administering CRT is not superior to continuing CT in patients with controlled LAPC after 4 months of CT. Clinical trial information: NCT00634725.

Final analysis of the PROMISE-GIM6 phase III trial assessing GnRH agonist use during chemotherapy as a strategy to preserve ovarian function in premenopausal patients with early breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 516-516
Author(s):  
Matteo Lambertini ◽  
Luca Boni ◽  
Andrea Michelotti ◽  
Emanuela Magnolfi ◽  
Alessio Aligi Cogoni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Ovarian Function ◽  
Final Analysis ◽  
Post Treatment ◽  
Phase Iii ◽  
Hormone Receptor Positive ◽  
Premenopausal Patients

516 Background: Current guidelines recommend GnRH agonist (GnRHa) use during chemotherapy (CT) as a strategy to reduce the risk of premature ovarian insufficiency (POI) in premenopausal patients with early breast cancer (EBC). However, no long-term safety data are available raising some concerns on concurrent use of GnRHa during CT in patients with hormone receptor-positive disease. In addition, there is no evidence on the protective role of this strategy in patients with germline BRCA mutations ( mBRCA). Here, we report the final analysis of the PROMISE-GIM6 phase III randomized study, the largest trial addressing the role of GnRHa use during CT in premenopausal EBC patients (Del Mastro et al, JAMA 2011 & Lambertini et al, JAMA 2015). Methods: From October 2003 to January 2008, 281 premenopausal patients aged 18 to 45 years with stage I-III EBC candidates for (neo)adjuvant CT were randomized to receive CT alone or combined with the GnRHa triptorelin. Primary endpoint was incidence of CT-induced POI (defined as amenorrhea and post-menopausal FSH/estradiol levels 1 year following CT). This final analysis reports on post-treatment pregnancies, disease-free survival (DFS) and overall survival (OS). An exploratory descriptive analysis in mBRCA patients is also reported. (ClinicalTrial.gov: NCT00311636) Results: Of the 281 randomized patients (CT+GnRHa arm = 148; CT alone arm = 133), 80% had hormone receptor-positive disease. At the time of this final analysis, 38 (13.5%) patients were lost to follow-up. Median follow-up was 12.4 years (IQR: 11.3-13.2 years). In the CT+GnRHa and CT alone arms, respectively, 9 (10-year cumulative incidence of pregnancy 6.5%, 95% CI 3.5%-12.3%) and 4 (10-year cumulative incidence of pregnancy 3.2%, 95% CI 1.2%-8.3%) patients had a post-treatment pregnancy (HR 2.14, 95% CI 0.66-6.92). No differences in 10-year DFS (72.4% in CT+GnRHa arm vs. 71.2% in CT alone arm: HR 1.16, 95% CI 0.76-1.77) nor in 10-year OS (82.0% in CT+GnRHa arm vs. 85.9% in CT alone arm: HR 1.17, 95% CI 0.67-2.03) were observed. There was no interaction between treatment effect and hormone receptor status. In patients with hormone receptor-positive disease, HR was 1.02 (95% CI 0.63-1.63) for DFS and 1.12 (95% CI 0.59-2.11) for OS. Out of 43 patients tested for BRCA, overall incidence of POI, irrespective of treatment arm, was 20% in mBRCA patients (n = 10) and 12% in patients without mBRCA (n = 33). In mBRCA patients, incidence of POI was 0% and 33% in the CT+GnRHa and CT alone arms, respectively. One post-treatment pregnancy was described in a patient with mBRCA1 in the CT alone arm. Conclusions: The final analysis of the PROMISE-GIM6 trial at a median follow-up of 12.4 years provides reassuring evidence on the safety of GnRHa use during CT as a strategy to preserve ovarian function in premenopausal patients with hormone receptor-positive EBC. Clinical trial information: NCT00311636.

Updated results of the GEST study: Randomized phase III study of gemcitabine plus S-1 (GS) versus S-1 versus gemcitabine (GEM) in unresectable advanced pancreatic cancer in Japan and Taiwan.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4035-4035 ◽  
Author(s):  
Akira Fukutomi ◽  
Takuji Okusaka ◽  
Kazuya Sugimori ◽  
Hideki Ueno ◽  
Tatsuya Ioka ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Primary Endpoint ◽  
Advanced Disease ◽  
Performance Status ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Locally Advanced Disease ◽  
Phase Iii Study

4035 Background: The GEST study (Ioka et al. ASCO 2011, Abstract 4007) demonstrated the non-inferiority of S-1 to GEM with respect to the primary endpoint of overall survival (OS) in patients with pancreatic cancer (PC). We now report the updated results of this study. Methods: The GEST study was a randomized, 3-arm, phase III study. Chemotherapy-naive patients with unresectable advanced PC, an ECOG Performance status (PS) of 0-1, and adequate organ functions were randomly assigned to receive GEM (1000 mg/m2, iv, d1, 8 and 15, q4w), S-1 (80/100/120 mg/day based on BSA, po, d1-28, q6w), or GS (GEM 1000 mg/m2, iv, d1 and 8 plus S-1 60/80/100 mg/day based on BSA po, d1-14, q3w). The primary endpoint was OS, used to assess the non-inferiority of S-1 and the superiority of GS to GEM. Patient information was updated in July 2011. Results: At the time of this follow-up analysis, median follow-up was 29.8 months with 795 OS events, compared with 18.4 months with 710 OS events out of 832 patients at the previous analysis. Median OS was 8.8 months (95% CI: 8.0–9.7) in the GEM group and 9.7 months (95% CI: 7.6-10.8) in the S-1 group (HR=0.96, 97.5% CI: 0.79-1.17, p<0.001 for non-inferiority), which is consistent with prior results (HR=0.96, 97.5% CI: 0.78-1.18, p<0.001). In the GS group, median OS was 9.9 months (95% CI: 9.0-11.2). The HR was 0.91 (97.5%CI: 0.75-1.11, p=0.28 for superiority versus the GEM group). On subgroup analysis, GS was associated with a non-statistically significant trend toward better OS compared with GEM among patients with locally advanced disease and those with a PS of 1. Median OS was 12.7 months (95% CI: 9.7–14.9) in the GEM group and 15.9 months (95% CI: 13.0-19.7) in the GS group (HR=0.72, 95% CI: 0.51-1.03) among patients with locally advanced disease, and 6.2 months (95% CI: 4.9–8.3) in the GEM group and 9.6 months (95% CI: 8.0-10.9) in the GS group (HR=0.62, 95% CI: 0.46-0.83) among patients with a PS of 1. Conclusions: The non-inferiority of S-1 to Gem in terms of the primary endpoint of OS was reconfirmed. Monotherapy with S-1 can be used as one of the standard treatments for advanced PC. As for GS therapy, there is room for further investigation.

Induction FOLFIRINOX followed by chemoradiation with capecitabine for unresectable locally advanced pancreatic cancer (LAPC): Preliminary data.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 458-458
Author(s):  
Rafael Ferreira de Carvalho ◽  
Erlon Gil ◽  
Raphael Brandao Moreira ◽  
Renata D'Alpino Peixoto ◽  
Marcus Paulo Fernandes Amarante ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Median Number ◽  
Sequential Treatment ◽  
Kaplan Meier ◽  
Metastatic Setting ◽  
Integrated Boost ◽  
Radiation Technique

458 Background: FOLFIRINOX was found to have higher response rates and overall survival (OS) compared to gemcitabine-based regimens in the metastatic setting. However, the contribution of chemoradiotherapy to outcomes after FOLFIRINOX in LAPC remains uncertain. We aim at evaluating our experience with FOLFIRINOX followed by chemoradiation (IMRT) with capecitabine for patients with LAPC. Methods: Patients with unresectable LAPC who received induction FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan and oxaliplatin) followed by chemoradiation with capecitabine at our institution were screened and accrued at the time of radiotherapy and are being followed prospectively. Radiation technique consisted of IMRT with simultaneous integrated boost (SIB) - dose of 45 Gy (1.8Gy/day) to high-risk lymph nodes and 55 Gy (2.2Gy/day) to the primary tumor. Progression-free survival (PFS) and OS were estimated by the Kaplan-Meier method. Results: Fourteen patients (58% female) were included in the analyses. Median age at diagnosis of LAPC was 61 years (range 38-78). Median number of FOLFIRINOX cycles was 11 (range 4-13). With a median follow up fo 11.7 months, 43% of the patients have died. Median PFS and OS were 15.9 (95% CI 6.8 – 25.1) and 16.7 months (95% CI 10.9 – 22.4), respectively. There were no treatment-related deaths. Conclusions: Our data suggest that sequential treatment with FOLFIRINOX followed by chemoradiation with capecitabine is feasible and may offer promising PFS and OS among selected patients with LAPC. Randomized trials are urgently needed to assess the role of sequential treatment in this population.

Planned interim analysis of the intergroup FFCD-GERCOR-FNCLCC-AERO phase III study comparing two sequences of chemotherapy in locally advanced or metastatic gastric cancers

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4533-4533 ◽  
Author(s):  
R. Guimbaud ◽  
O. Bouché ◽  
C. Rebischung ◽  
F. Bonnetain ◽  
C. Louvet ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Locally Advanced ◽  
Final Analysis ◽  
Phase Iii ◽  
Rank Test ◽  
Test Results ◽  
Significance Level ◽  
Kaplan Meier ◽  
Phase Iii Study ◽  
Grade 3

4533 Background: There are several standard chemotherapies in locally advanced or metastatic gastric or cardia adenocarcinoma, including ECF. Methods: Patients (pts) with a gastric or cardiac adenocarcinoma, locally advanced or metastatic, not surgically curable, with a WHO PS ≤2 and evaluable or measurable lesions, were randomized (1:1) according to the following sequences: ECC (epirubicin 50 mg/m2 D1+ cisplatin 60 mg/m2 D1 + capecitabine 2000 mg/m2 D2 to D15, every 3 weeks) in 1st line, then FOLFIRI (IRI 180 mg/m2 D1, leucovorin 400 mg/m2 D1, bolus 5FU 400 mg/m2 D1 and continuous 5FU 2400 mg/m2 in 46h, every 2 weeks) in 2nd line (Arm A) vs the reverse sequence (Arm B) with a stratification for center, PS, adjuvant treatment, site, linitis and measurable disease. To show an improvement in median time to treatment failure for the 1st line (TTF: time between randomization and progression, or treatment discontinuation or recurrence or death) of 15 to 20 weeks for arm B (α bilateral 5%; β 20 %), 381 failures and 416 pts are required in 4-year period. An interim analysis is planned when at least 190 failures are observed (ITT). TTF is estimated according to the Kaplan Meier method and compared with a Log-rank test. Results: In arm A and B, 174 and 175 pts were included respectively, between 17/06/05 and 21/12/07. Pts characteristics are: PS 1: 51%, med. age 60 years, gastric 67%, M+ 88%, resected primary tumor 27% and linitis 23%. In arms A and B respectively, 141 and 147 pts received at least one dose in 1st line and 61 and 44 pts in 2nd line. Toxicities during the first line is more frequent in the ECC than in the FOLFIRI arm: grade 3/4 (88 vs 68% - p ≤0.0001) and grade 3/4 hemato toxicities (69 vs 36% - p ≤0.001). In 2nd line, toxicities frequency is not different in both arms. The median TTF in 1st line (n = 310 pts) is 4.7 months [3.8 - 5.7] for ECC and 5.2 months [4.4–6.0] for FOLFIRI (Log Rank p = 0. 78). Regarding the 252 failures observed (67% of the required events), the significance level to reject H0 is p = 0.012 (EAST V5). Conclusions: It is not possible yet to conclude to the superiority of FOLFIRI in 1st line; the final analysis after observation of 381 failures is required. Regarding toxicity, hemato-toxicity is more frequent with ECC in 1st line. [Table: see text]

R-CHOP14 compared to R-CHOP21 in elderly patients with diffuse large B-cell lymphoma (DLBCL): Final analysis of the LNH03-6B GELA study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8021-8021 ◽  
Author(s):  
Richard Delarue ◽  
Herve Tilly ◽  
Gilles A. Salles ◽  
Catherine Thieblemont ◽  
Nicolas Mounier ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Dose Intensity ◽  
B Cell Lymphoma ◽  
Final Analysis ◽  
Similar Efficacy ◽  
Primary Objective ◽  
Phase Iii ◽  
Median Dose ◽  
Serious Adverse Event

8021 Background: In 2000, the GELA established a new standard for elderly patients with DLBCL, demonstrating survival advantage of R-CHOP21 over CHOP21. Based on RICOVER-60 results, the DSHNHL proposed R-CHOP14 as a standard. Comparison between both regimens is lacking. We report the results of the final analysis of the randomized phase III trial LNH03-6B, with a median follow-up of 56 months. Methods: Pts between 60 and 80 years old with DLBCL and aaIPI≥1 were eligible. They were randomized between R-CHOP14 and R-CHOP21 for 8 cycles. G-CSF prophylaxis was given according to physician decision. Primary objective was to evaluate the efficacy of R-CHOP14 compared to R-CHOP21 as measured by the EFS. Results: 602 pts were randomized, 600 were evaluable, 304 with R-CHOP14 and 296 with R-CHOP21. Median age was 70 years. Pts characteristics were similar between the two arms. Percentage of pts with baseline IPI3-5 was 72% in R-CHOP14 arm and 78% in R-CHOP21 arm. Median interval between 2 cycles was 14 d in R-CHOP14 arm and 21 d in R-CHOP21 arm. In R-CHOP14 arms, 89% of cycles were administered with G-CSF. Median dose-intensity for R-CHOP14 arm was 88% for cyclophosphamide and doxorubicin. There was no difference in median dose-intensity according to G-CSF administration at first cycle. Response rate (CR+CRu) was 71% in R-CHOP14 arm and 74% in R-CHOP21 arm (p=0.42). The 3-y EFS was 56% in R-CHOP14 arm and 60% in R-CHOP21 (HR 1.04; CI95% 0.82-1.31; p=0.79). Moreover, there is no difference between both arms regarding 3-y PFS (60% vs. 62%; HR 0.99; CI95% 0.78-1.26; p=0.90), DFS (72% vs. 67%; HR 0.80; CI95% 0.58-1.10; p=0.80) and OS (69% vs. 72%; HR 0.96; CI95% 0.73-1.26; p=0.75). Finally, percentage of patients with at least one serious adverse event (R-CHOP14: 51%; R-CHOP21: 47%) and rate of toxic death (4.6% and 4.7% respectively) were similar. Conclusions: Results of the final analysis of LNH03-6B demonstrate similar efficacy and safety profile between R-CHOP14 and R-CHOP21.

A double-blind, placebo-controlled, randomized phase III trial of gemcitabine (G) plus bevacizumab (B) versus gemcitabine plus placebo (P) in patients (pts) with advanced pancreatic cancer (PC): A preliminary analysis of Cancer and Leukemia Group B (CALGB

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4508-4508 ◽  
Author(s):  
H. L. Kindler ◽  
D. Niedzwiecki ◽  
D. Hollis ◽  
E. Oraefo ◽  
D. Schrag ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Stage Iv ◽  
Final Analysis ◽  
Bleeding Risk ◽  
Phase Iii ◽  
Double Blind ◽  
Disease Extent ◽  
Phase Iii Trial ◽  
Double Blind Placebo

4508 Background: In a phase II trial in 52 PC pts, GB yielded a 21% response rate and a median survival of 8.8 months (mo) (Kindler, JCO 2005). These data led CALGB to conduct a phase III trial of GB vs. GP in advanced PC pts. Methods: This randomized trial was double-blind, placebo-controlled. Eligible pts had no prior therapy for advanced disease, PS 0–2, no tumor invasion of adjacent organs, no increased bleeding risk. Primary endpoint: overall survival (OS). Stratification: PS (0/1 or 2), disease extent (locally advanced or metastatic), prior radiation (RT) (yes/no). Statistics: 90% power to detect a difference in median OS of 6 vs. 8.1 mo. Treatment: Pts received G 1,000 mg/m2 over 30 minutes days (D) 1, 8, 15 Q28D; B 10 mg/kg or P D 1, 15 Q28D. CT scans: Q2 cycles. Results: 602 pts enrolled 6/30/04–4/14/06. Based on a protocol-specified interim analysis with 64% of information on OS, the CALGB Data Safety Monitoring Board released study data in 6/06 because a futility boundary was crossed. Pts on treatment were notified and unblinded. Pt characteristics (302GB/300GP): male 58%/51%; median age 63.8/65.0; PS 2 9%/9%; stage IV 85%/84%; prior RT 11%/11%. Median follow-up: 11.3/11.7 mo. As of 12/22/06, 436 pts (224/212) have died (93% of total expected deaths at planned final analysis). Median OS 5.7/6.0 mo (95% CI: 4.9, 6.5/5.0, 6.9). Median failure-free survival 4.8/4.3 mo (95% CI: 4.3, 5.7/3.8, 5.6). Response (includes unconfirmed responses): complete (CR) 1.9%/3.0%; partial (PR) 11.2%/8.3%, stable disease (SD) 40.7%/35.7%. Disease control rate (CR/PR/SD) 54%/47%. 525 pts (268/257) are currently evaluable for toxicity. Median cycles 3.5/3.1 (p=0.09). Total mg/m2 G received 9095/8334 (p=0.22). Grade ¾ toxicity (%pts GB/GP): neutropenia 33%/30%; anemia 5%/8%; thrombocytopenia 12%/12%; hypertension 8%/2%; perforation 0.4%/0%; GI bleed 3%/2%; CVA 2%/2%; proteinuria 4%/1%; venous thrombosis 9%/9%. Conclusion: The addition of B to G does not improve survival in advanced PC. [Table: see text]

A phase II trial of ZD6474 plus docetaxel in patients with previously treated NSCLC: Follow-up results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7016-7016 ◽  
Author(s):  
J. V. Heymach ◽  
B. E. Johnson ◽  
D. Prager ◽  
E. Csada ◽  
J. Roubec ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Survival Data ◽  
Locally Advanced ◽  
Primary Objective ◽  
Phase Iii ◽  
Double Blind Study ◽  
Once Daily ◽  
Platinum Based Chemotherapy

7016 Background: ZD6474, a once-daily oral agent, targets key signaling pathways in cancer by inhibiting VEGF, EGF and RET receptor tyrosine kinases. ZD6474 in combination with docetaxel (Doc) was assessed in patients (pts) with refractory non-small-cell lung cancer (NSCLC). Methods: Pts eligible for this randomized, double-blind study had locally advanced or metastatic (stage IIIB/IV) NSCLC after failure of 1st-line platinum-based chemotherapy. The primary objective was to determine whether once-daily oral ZD6474 (100 or 300 mg) + Doc (75 mg/m2 i.v. infusion every 21 days) prolonged progression-free survival (PFS) vs Doc alone (80% power to detect 50% prolongation at P<0.2). Overall survival was a secondary objective. Results: A total of 127 pts (73 male/54 female; median age 59 yrs, range 29–82) received ZD6474 100 mg + Doc (n=42), ZD6474 300 mg + Doc (n=44) or Doc (n=41). The study met its primary objective of PFS prolongation with the addition of ZD6474: median PFS was 19 wks for ZD6474 100 mg + Doc (HR=0.64; P=0.074); 17 wks for ZD6474 300 mg + Doc (HR=0.83; P=0.461); and 12 wks for Doc. A total of 64 pts (50%) presented with histology other than adenocarcinoma, including 37 with squamous, and 13 pts (10%) entered with CNS metastases. Exploratory subgroup analyses suggest advantages in PFS for ZD6474 + Doc vs Doc both for adenocarcinoma and for other lung cancer histologies. Common adverse events (AEs) included diarrhea, rash and asymptomatic QTc prolongation, all responded to standard management or dose interruption/reduction. Four pts with squamous experienced hemoptysis (ZD6474 100 mg + Doc, n=2 CTC grade 1/2; Doc, n=2 CTC grade 3/4). No fatal episodes of hemoptysis or any CNS hemorrhage AEs were reported in pts receiving ZD6474. Overall survival data were immature at the time of PFS analysis, and a mature survival analysis will be conducted at ∼75% of deaths (anticipated April 2006, and will be presented at the meeting). As of December 2005, 40/127 (31%) pts were alive, 5 of whom continue to receive ZD6474. The minimum follow-up of pts still alive was 17 months. Conclusions: ZD6474 + Doc prolonged PFS vs Doc alone, and these promising data have led to the initiation of Phase III evaluation of ZD6474 + Doc in 2nd-line NSCLC. [Table: see text]

Efficacy of oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX4) versus doxorubicin in advanced HCC: Updates on the EACH study.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 160-160 ◽  
Author(s):  
S. Thongprasert ◽  
S. Qin ◽  
H. Lim ◽  
V. Bhudhisawasdi ◽  
X. Yin ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Locally Advanced ◽  
Safety Data ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Rank Test ◽  
Open Label ◽  
Advanced Hcc

160 Background: In Asia, where hepatitis B is very common, patients often present with locally advanced or metastatic hepatocellular carcinoma (HCC), and their prognosis is poor. The EACH study was designed to evaluate the efficacy and safety of FOLFOX4 vs. doxorubicin as palliative systemic chemotherapy in advanced HCC. Methods: The open-label, randomized, multicenter phase III study was conducted in 371 patients in China, Taiwan, Korea and Thailand, who had locally advanced or metastatic HCC and were ineligible for resection. Patients were randomized 1:1 to receive either FOLFOX4 (oxaliplatin 85 mg/m2 i.v. d1; LV 200 mg/m2 i.v. h0–h2 d1 and d2; 5FU 400 mg/m2 i.v. bolus h2, then 600 mg/m2 over 22 hours d1 and d2 q2w) or doxorubicin (50 mg/m2 i.v. q3w). The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), response rate (RR) by RECIST and safety. Data from final and follow-up analyses of the intent-to-treat (ITT) population and selected subgroup analyses are presented. Results: At the final analysis, median OS with FOLFOX4 (N = 184) was 6.40 months (95% CI: 5.30, 7.03) vs. 4.97 months (95% CI: 4.23, 6.03) with doxorubicin [N = 187; p = 0.0695 using a stratified log-rank test; statistical significance (p = 0.0425) was achieved at the post hoc follow-up analysis conducted 7 months later]. Median PFS with FOLFOX4 was 2.93 months (95% CI: 2.43, 3.53) vs. 1.77 months with doxorubicin (95% CI: 1.63, 2.30; p = 0.0002). The RR was 8.2% vs. 2.7% of patients with FOLFOX4 and doxorubicin, respectively (p = 0.0233), and the disease control rate (DCR) was 52.2% vs. 31.6% (p < 0.0001). In the Chinese sub-population, OS, PFS, RR and DCR were significantly improved with FOLFOX4 vs. doxorubicin at both the final and follow-up analyses. In the other subgroups analyzed, the OS and PFS benefits of FOLFOX4 vs. doxorubicin were generally consistent. Conclusions: In the ITT population, median OS was greater with FOLFOX4 than doxorubicin throughout the study and statistical significance was achieved after continued follow-up. FOLFOX4 can benefit patients with advanced HCC, as it significantly increases median OS, PFS, RR and DCR compared with doxorubicin. [Table: see text]

The Role of Atrial Fibrosis Detected by Delayed - Enhancement MRI in Atrial Fibrillation Ablation

2020 ◽  
Vol 16 (2) ◽  
pp. 135-144 ◽  
Author(s):  
Zsuzsanna Kis ◽  
Astrid Amanda Hendriks ◽  
Taulant Muka ◽  
Wichor M. Bramer ◽  
Istvan Kovacs ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Imaging Modality ◽  
Final Analysis ◽  
Atrial Fibrosis ◽  
Atrial Wall ◽  
Af Ablation ◽  
Left Atrial Wall ◽  
Cmr Imaging

Introduction: Atrial Fibrillation (AF) is associated with remodeling of the atrial tissue, which leads to fibrosis that can contribute to the initiation and maintenance of AF. Delayed- Enhanced Cardiac Magnetic Resonance (DE-CMR) imaging for atrial wall fibrosis detection was used in several studies to guide AF ablation. The aim of present study was to systematically review the literature on the role of atrial fibrosis detected by DE-CMR imaging on AF ablation outcome. Methods: Eight bibliographic electronic databases were searched to identify all published relevant studies until 21st of March, 2016. Search of the scientific literature was performed for studies describing DE-CMR imaging on atrial fibrosis in AF patients underwent Pulmonary Vein Isolation (PVI). Results: Of the 763 citations reviewed for eligibility, 5 articles (enrolling a total of 1040 patients) were included into the final analysis. The overall recurrence of AF ranged from 24.4 - 40.9% with median follow-up of 324 to 540 days after PVI. With less than 5-10% fibrosis in the atrial wall there was a maximum of 10% recurrence of AF after ablation. With more than 35% fibrosis in the atrial wall there was 86% recurrence of AF after ablation. Conclusion: Our analysis suggests that more extensive left atrial wall fibrosis prior ablation predicts the higher arrhythmia recurrence rate after PVI. The DE-CMR imaging modality seems to be a useful method for identifying the ideal candidate for catheter ablation. Our findings encourage wider usage of DE-CMR in distinct AF patients in a pre-ablation setting.

scholarly journals The Role of Surgery in Lung Cancer Treatment: Present Indications and Future Perspectives—State of the Art

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3711
Author(s):  
François Montagne ◽  
Florian Guisier ◽  
Nicolas Venissac ◽  
Jean-Marc Baste
Keyword(s):  
Lung Cancer ◽  
Residual Disease ◽  
State Of The Art ◽  
Locally Advanced ◽  
Small Cell Lung ◽  
Lung Cancers ◽  
Screening Programs ◽  
Systemic Therapies

Non-small cell lung cancers (NSCLC) are different today, due to the increased use of screening programs and of innovative systemic therapies, leading to the diagnosis of earlier and pre-invasive tumors, and of more advanced and controlled metastatic tumors. Surgery for NSCLC remains the cornerstone treatment when it can be performed. The role of surgery and surgeons has also evolved because surgeons not only perform the initial curative lung cancer resection but they also accompany and follow-up patients from pre-operative rehabilitation, to treatment for recurrences. Surgery is personalized, according to cancer characteristics, including cancer extensions, from pre-invasive and local tumors to locally advanced, metastatic disease, or residual disease after medical treatment, anticipating recurrences, and patients’ characteristics. Surgical management is constantly evolving to offer the best oncologic resection adapted to each NSCLC stage. Today, NSCLC can be considered as a chronic disease and surgery is a valuable tool for the diagnosis and treatment of recurrences, and in palliative conditions to relieve dyspnea and improve patients’ comfort.

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