Liposomal doxorubicin and cisplatin as first-line chemotherapy in unresectable malignant pleural mesothelioma: A phase II study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13507-e13507
Author(s):  
O. Arrieta ◽  
L. A. Medina ◽  
E. Guzmán ◽  
M. A. Rios Trejo ◽  
D. Mendoza ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Liposomal Doxorubicin ◽  
Tumor Tissue ◽  
Good Prognosis ◽  
Phase Iii ◽  
Stage Iii ◽  
Pleural Mesothelioma ◽  
Highly Active ◽  
Initial Injection

e13507 Background: Malignant pleural mesothelioma (MPM) is a poor prognosis neoplasm. Its worldwide incidence is rising but until recently chemotherapy has not been shown to be effective in its treatment. The combination of cisplatin and pemetrexed is the approved “standard” treatment in unresectable MPM. Liposomal doxorubicin (LD) consists of pegylated phospholipid- vesicles that encapsulate doxorubicin conferring minimal capture from the reticulo-endothelial system resulting in a greater serum half- life, an enhanced liposome deposition in the tumor and a lower degree of toxicity. We evaluated the combination of LD and Cisplatin (Cis) in chemonaive patients with unresectable MPM. Methods: From September 2006 to October 2008, consecutive patients with stage III / IV MPM were included to receive LD 40 mg/m2 and Cis 60 mg/m2 every 21 days for a maximum of 4 cycles. Imaging studies were performed prior and after 2 cycles to assess response. Gamma camera images (GCI) of Tc-99m-labeled LD were acquired to evaluate LD accumulation in measurable tumor tissue. Patients gave written informed consent. Results: Twenty seven patients were included, 81.5% were stage III and 18.5% were IV. According to EORTC prognostic factors, 33.3% and 66.7% had poor and good prognosis, respectively. Median age was 59.2 years (33–80). Median follow-up was of 5.2 ± 0.8 months. Median survival has not been reached. The 2-year overall survival was 52.5% ± 14.2. Median time to progression was 5.0 ± 1.1 months (CI 95%, 2.7–7.3). Overall response was 45.5%, stable disease 36.4% and progression of 18.2%. GCI showed good accumulation and retention (60%) of the labeled LD in tumor tissue at 4 h after the initial injection. There were no toxic deaths. Conclusions: Cis+LD is a highly active regimen in MPM with comparable results to the most active regimens so far reported. A phase III trial is warranted to confirm these findings. No significant financial relationships to disclose.

scholarly journals PROGNOSTIC VALUES OF MIDKINE, SYNDECAN-1, HYALURONAN SYNTHASE-2, SESTRIN-1, LAMININ SUBUNIT ALPHA-4 AND FIBULIN-3 FOR MALIGNANT PLEURAL MESOTHELIOMA

2021 ◽  
Author(s):  
HAKAN AKGUN ◽  
Selma Metintas ◽  
Guntulu Ak ◽  
Secil Demirkol ◽  
Murat Isbilen ◽  
...  
Keyword(s):  
Survival Time ◽  
Malignant Pleural Mesothelioma ◽  
Multivariate Analyses ◽  
Ex Vivo ◽  
Relevant Literature ◽  
Good Prognosis ◽  
Hyaluronan Synthase ◽  
Pleural Mesothelioma ◽  
Analysis Tool ◽  
Hyaluronan Synthase 2

IntroductionThe prognosis of malignant pleural mesothelioma (MPM) is poor with a limited survival time. In this study, we aimed to examine expression levels of genes selected from relevant literature and to utilize in silico methods to determine genes whose expression could reflect the prognosis of the patients with MPM by ex-vivo validation experimentsMaterial and methodsThe study group consisted of 54 MPM patients treated by chemotherapy. Expression of 6 genes; midkine (MDK), syndecan 1 (SDC1), hyaluronan synthase 2 (HAS2), sestrin 1 (SESN1), laminin subunit alpha 4 (LAMA4), and fibulin 3 (FBLN3) were examined by qPCR in tumor tissues. SESN1 and LAMA4 were identified using an in house R-based script “Unsupervised Survival Analysis Tool." MDK, SDC1, HAS2, and FBLN3 were selected from current literature. We used two housekeeping genes; glucose-6-phosphate dehydrogenase and TATA-box binding protein as controls.ResultsOf the patients, 43 (79.6%) had epithelioid mesothelioma. The median survival for all patients was 10 (±1.2 SE) months (CI 95%; 7.7-12.3). In multivariate analyses, MDK (p=0.007), HAS2 (p=0.008) and SESN1 (p=0.014) expression were related with survival time in whole group. In epithelioid type MPM patients, MDK (p=0.014), FBLN3 (p=0.029), HAS2 (p=0.014) and SESN1 (p=0.045) expression was related with survival time by multivariate analyses.ConclusionsHigh HAS2 and SESN1 expressions and low MDK are potential biomarkers of good prognosis in MPM. High HAS2 and SESN1 expression and low MDK and FBLN3 can also be utilized as biomarkers of good prognosis for epithelioid MPM. Those results should be further investigated in sera, plasma, and pleural effusions

Radical pleurectomy/decortication followed by high dose of radiation therapy for malignant pleural mesothelioma. Final results with long-term follow-up

Lung Cancer ◽  
2014 ◽  
Vol 83 (1) ◽  
pp. 78-82 ◽  
Author(s):  
Emilio Minatel ◽  
Marco Trovo ◽  
Jerry Polesel ◽  
Tania Baresic ◽  
Alessandra Bearz ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Malignant Pleural Mesothelioma ◽  
High Dose ◽  
Pleural Mesothelioma ◽  
Long Term Follow Up

scholarly journals Longer Follow-Up Confirms Recurrence-Free Survival Benefit of Adjuvant Pembrolizumab in High-Risk Stage III Melanoma: Updated Results From the EORTC 1325-MG/KEYNOTE-054 Trial

2020 ◽  
Vol 38 (33) ◽  
pp. 3925-3936 ◽  
Author(s):  
Alexander M. M. Eggermont ◽  
Christian U. Blank ◽  
Mario Mandala ◽  
Georgina V. Long ◽  
Victoria G. Atkinson ◽  
...  
Keyword(s):  
Lymph Node ◽  
High Risk ◽  
Phase Iii ◽  
Stage Iii ◽  
Recurrence Free Survival ◽  
Meaningful Improvement ◽  
Free Survival ◽  
Stage Iii Melanoma ◽  
The Impact

PURPOSE We conducted the phase III double-blind European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial to evaluate pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. On the basis of 351 recurrence-free survival (RFS) events at a 1.25-year median follow-up, pembrolizumab prolonged RFS (hazard ratio [HR], 0.57; P < .0001) compared with placebo. This led to the approval of pembrolizumab adjuvant treatment by the European Medicines Agency and US Food and Drug Administration. Here, we report an updated RFS analysis at the 3.05-year median follow-up. PATIENTS AND METHODS A total of 1,019 patients with complete lymph node dissection of American Joint Committee on Cancer Staging Manual (seventh edition; AJCC-7), stage IIIA (at least one lymph node metastasis > 1 mm), IIIB, or IIIC (without in-transit metastasis) cutaneous melanoma were randomly assigned to receive pembrolizumab at a flat dose of 200 mg (n = 514) or placebo (n = 505) every 3 weeks for 1 year or until disease recurrence or unacceptable toxicity. The two coprimary end points were RFS in the overall population and in those with programmed death-ligand 1 (PD-L1)–positive tumors. RESULTS Pembrolizumab (190 RFS events) compared with placebo (283 RFS events) resulted in prolonged RFS in the overall population (3-year RFS rate, 63.7% v 44.1% for pembrolizumab v placebo, respectively; HR, 0.56; 95% CI, 0.47 to 0.68) and in the PD-L1–positive tumor subgroup (HR, 0.57; 99% CI, 0.43 to 0.74). The impact of pembrolizumab on RFS was similar in subgroups, in particular according to AJCC-7 and AJCC-8 staging, and BRAF mutation status (HR, 0.51 [99% CI, 0.36 to 0.73] v 0.66 [99% CI, 0.46 to 0.95] for V600E/K v wild type). CONCLUSION In resected high-risk stage III melanoma, pembrolizumab adjuvant therapy provided a sustained and clinically meaningful improvement in RFS at 3-year median follow-up. This improvement was consistent across subgroups.

scholarly journals Glycodelin is a potential novel follow-up biomarker for malignant pleural mesothelioma

Oncotarget ◽  
2016 ◽  
Vol 7 (44) ◽  
pp. 71285-71297 ◽  
Author(s):  
Marc A. Schneider ◽  
Thomas Muley ◽  
Nicolas C. Kahn ◽  
Arne Warth ◽  
Michael Thomas ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Pleural Mesothelioma

Mabthera (Rituximab) Plus CVP Chemotherapy for First-Line Treatment of Stage III/IV Follicular Non-Hodgkin’s Lymphoma (NHL): Confirmed Efficacy with Longer Follow-Up.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 350-350 ◽  
Author(s):  
Philippe Solal-Celigny ◽  
Kevin Imrie ◽  
Andrew Belch ◽  
Katherine Sue Robinson ◽  
David Cunningham ◽  
...  
Keyword(s):  
Risk Factors ◽  
Disease Progression ◽  
Phase Iii ◽  
Stage Iii ◽  
Line Treatment ◽  
First Line ◽  
Time To Death ◽  
Kaplan Meier ◽  
First Line Treatment

Abstract Design/Methods: We recently demonstrated in a phase III trial that the addition of rituximab to each of 8 cycles of CVP (R-CVP) chemotherapy significantly improves the clinical outcome of previously untreated patients with stage III/IV CD20 positive follicular NHL when compared to CVP alone (Marcus et al., Blood2005; 105: 1417–23). A multivariate Cox regression analysis of time to progression or death (TTP) showed a treatment benefit in all patient subgroups according to baseline risk factors, except for patients with a baseline hemoglobin level below normal. We now present an updated analysis of all major trial endpoints with 42 months follow-up (FU). Results: A total of 321 patients (median age 53 years) were recruited (159 CVP, 162 R-CVP). Approximately half of the patients had high-risk disease according to the Follicular Lymphoma International Prognostic Index (FLIPI, score 3–5). The median TTP was more than doubled for patients receiving R-CVP compared to CVP alone (33.6 months vs 14.5 months, p&lt;0.0001). Median time to new lymphoma treatment or death (TNLT) was 12.3 months in the CVP group and nearly quadrupled to 46.3 months in the R-CVP group (p&lt;0.0001). Superior response rates for R-CVP were confirmed (CR+CRu rate 41% vs 11%, p&lt;0.0001) with a median response duration (DR) of 13.5 months in the CVP arm versus 37.7 months in the R-CVP arm. Median disease free survival (DFS) in complete responders was 44.8 months for patients receiving R-CVP and 20.5 months in patients receiving CVP alone (p=0.0005). Thirty-five patients in the CVP arm and 23 patients in the R-CVP arm have died. Kaplan-Meier estimates of 3-year OS rates were 81% in the CVP arm and 89% in the R-CVP (p=0.07). Importantly, significantly more patients receiving CVP died due to lymphoma progression compared to patients receiving R-CVP (25 vs 12 deaths, p=0.02). Subgroup analysis for TTP, ORR, DR and OS according to risk factors at baseline are ongoing and will be presented. Conclusion: With longer FU, the combination of 8 cycles of rituximab with CVP chemotherapy continues to provide a major benefit as first line treatment for patients with advanced stage follicular NHL. Kaplan Meier plot of time to death due to disease progression Kaplan Meier plot of time to death due to disease progression

A randomized phase III trial of active symptom control (ASC) with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma: First results of the Medical Research Council (MRC) / British Thoracic Society (BTS) MS01 trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. LBA7525-LBA7525 ◽  
Author(s):  
M. Muers ◽  
P. Fisher ◽  
M. Snee ◽  
E. Lowry ◽  
M. O'Brien ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Median Survival ◽  
Malignant Pleural Mesothelioma ◽  
Survival Benefit ◽  
Phase Iii ◽  
Pleural Mesothelioma ◽  
Significant Survival Benefit ◽  
Significant Survival ◽  
Symptom Palliation ◽  
Weekly Cycles

LBA7525 Background: Although chemotherapy is widely used in the treatment of mesothelioma it has never been compared in a randomized trial with ASC alone. Two chemotherapy regimens that had shown good symptom palliation in phase II studies were chosen for investigation. Methods: Patients with malignant pleural mesothelioma were randomized to ASC alone (regular follow-up in a specialist clinic, and treatment could include steroids, analgesics, bronchodilators, palliative radiotherapy, etc), ASC+MVP (4 × 3-weekly cycles of mitomycin 6g/m2, vinblastine 6mg/m2, and cisplatin 50mg/m2), or ASC+N (12 weekly injections of vinorelbine 30mg/m2). 420 patients were required to detect a 3-month improvement in median survival with ASC+CT (both chemotherapy arms combined). Quality of Life (QL) was assessed using the EORTC QLQ-C30. Results: 409 patients were accrued (136 ASC, 137 ASC+MVP, 136 ASC+N). Median age: 65 years, male: 91%, Performance status 0: 23%, Epithelial histology: 73%, Stage III: 33%, Stage IV: 48%. In the ASC+MVP group 61% received all 4 cycles, and in the ASC+N group 49% received at least 10 weekly cycles. Good symptom palliation (defined as prevention, control or improvement) was achieved in all 3 groups, and no between-group differences were observed in 4 pre-defined QL subscales (physical functioning, dyspnoea, pain and global QL). A small (not conventionally significant) survival benefit was seen for ASC+CT (349 deaths, HR 0.89, 95%CI 0.72, 1.12, p=0.32). Median survival: ASC: 7.6 months, ASC+CT: 8.5 months. Exploratory analyses suggested a survival advantage for vinorelbine compared to ASC alone (HR 0.81, 95%CI 0.63, 1.05, p=0.11), with a median survival of 9.4 months, but no evidence of a benefit with MVP (HR 0.98, 95%CI 0.76, 1.28), p=0.91). Conclusions: This is the 2nd largest ever randomized trial in mesothelioma and the first to compare ASC with or without chemotherapy. Although the addition of chemotherapy to ASC did not result in a conventionally significant survival benefit, there was an indication that vinorelbine should be investigated further, and that MVP probably has no role in this disease. [Table: see text]

Pembrolizumab versus placebo after complete resection of high-risk stage III melanoma: New recurrence-free survival results from the EORTC 1325-MG/Keynote 054 double-blinded phase III trial at three-year median follow-up.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10000-10000 ◽  
Author(s):  
Alexander M. Eggermont ◽  
Christian U. Blank ◽  
Mario Mandalà ◽  
Georgina V. Long ◽  
Victoria Atkinson ◽  
...  
Keyword(s):  
Lymph Node ◽  
High Risk ◽  
Complete Resection ◽  
Phase Iii ◽  
Stage Iii ◽  
Recurrence Free Survival ◽  
Stage Iiia ◽  
Free Survival ◽  
Stage Iii Melanoma

10000 Background: We conducted the phase 3 double-blind EORTC 1325/KEYNOTE-054 trial to evaluate pembrolizumab vs placebo in patients (pts) with resected high-risk stage III melanoma. Based on 351 recurrence-free survival (RFS) events and at a median follow-up of 1.25 years (yrs), pembrolizumab improved RFS (hazard ratio (HR) 0.57, P<0.0001) as compared to placebo (Eggermont, NEJM 2018). This led to the approval of pembrolizumab adjuvant treatment by EMA and FDA. Methods: Eligible pts included those ≥18 yrs of age with complete resection of cutaneous melanoma metastatic to lymph node(s), classified as AJCC-7 stage IIIA (at least one lymph node metastasis >1 mm), IIIB or IIIC (without in-transit metastasis). A total of 1019 pts were randomized (stratification by stage and region) to pembrolizumab at a flat dose of 200 mg (N=514) or placebo (N=505) every 3 weeks for a total of 18 doses (~1 year) or until disease recurrence or unacceptable toxicity. The 2 co-primary endpoints were RFS in the intention-to-treat overall population and in pts with PD-L1-positive tumors. Here, we report an updated RFS analysis based on a longer follow-up. Results: Overall, 15%/46%/39% of pts had stage IIIA/IIIB/IIIC. At 3.05-yr median follow-up, pembrolizumab (190 RFS events) compared with placebo (283 RFS events) prolonged RFS, in the overall population and in the PD-L1 positive tumor subgroup (see Table). RFS was consistently prolonged across subgroups, in particular according to AJCC-7 staging, BRAF-V600 E/K mutation status. Conclusions: Pembrolizumab, administered at 200 mg every 3 weeks for up to 1 year as adjuvant therapy, provided, at a 3-yr median follow-up, a sustained improvement in RFS, which was clinically meaningful, in resected high-risk stage III melanoma. This improvement was consistent across subgroups. In the overall population, the 3-yr cumulative incidence of distant metastasis being the first recurrence was 22.3% (pembrolizumab group) vs 37.3% (placebo group) (HR 0.55, 95% CI 0.44-0.69). Clinical trial information: NCT02362594. [Table: see text]

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