The Experts below are selected from a list of 28887 Experts worldwide ranked by ideXlab platform
Heinzjosef Lenz - One of the best experts on this subject based on the ideXlab platform.
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gene polymorphisms of ccl3 ccl4 ccl5 and ccr5 network in Metastatic Colorectal Cancer patients treated with regorafenib
Journal of Clinical Oncology, 2020Co-Authors: Mitsukuni Suenaga, Yuji Miyamoto, Wu Zhang, Tetsuo Mashima, Marta Schirripa, Shu Cao, Satoshi Okazaki, Martin D Berger, Afsaneh Barzi, Heinzjosef LenzAbstract:199Background: We previously reported that genetic variant in the CCL5/CCR5 pathway predict efficacy of regorafenib in Metastatic Colorectal Cancer patients (mCRC). CCL5 rs2280789 G allele and CCL5...
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results from a phase i study of andecaliximab in combination with folfiri and bevacizumab in patients with second line Metastatic Colorectal Cancer
Journal of Clinical Oncology, 2018Co-Authors: Zev A Wainberg, Heinzjosef Lenz, Jordan Berlin, Ari David Baron, Johanna C Bendell, Alberto Bessudo, Daniel Bruetman, Ki Y Chung, Haeseong Park, Manish R PatelAbstract:3578Background: Matrix metalloproteinase 9 is highly expressed in several malignancies, including Metastatic Colorectal Cancer (mCRC) and is an adverse prognostic feature. In preclinical Colorectal...
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randomized trial of irinotecan and cetuximab with or without vemurafenib in braf mutant Metastatic Colorectal Cancer swog s1406
Journal of Clinical Oncology, 2017Co-Authors: Scott Kopetz, Yibing Yan, Katherine A Guthrie, Van K Morris, Heinzjosef Lenz, Anthony M Magliocco, Dipen M Maru, Richard B Lanman, Ganiraju C Manyam, David S HongAbstract:PURPOSEBRAFV600E mutations are rarely associated with objective responses to the BRAF inhibitor vemurafenib in patients with Metastatic Colorectal Cancer (CRC). Blockade of BRAFV600E by vemurafenib...
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a novel antimetabolite tas 102 for Metastatic Colorectal Cancer
Expert Review of Clinical Pharmacology, 2016Co-Authors: Yuji Miyamoto, Heinzjosef Lenz, Hideo BabaAbstract:TAS-102 is a new oral anti-tumor drug, composed of a thymidine-based nucleoside analog (trifluridine: FTD) and a thymidine phosphorylase inhibitor (tipiracil hydrochloride: TPI). TAS-102 has been shown to significantly improve overall survival and progression-free survival in patients with refractory Metastatic Colorectal Cancer (mCRC) in placebo-controlled randomized phase II and III trials. The current review summarizes mechanisms of action, pharmacokinetics/dynamics and preclinical and clinical data of TAS-102 in Colorectal Cancer. TAS-102 is a new salvage-line treatment option for patients with mCRC. TAS-102 is well tolerated and has great potential in future clinical drug combination therapies.
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a let 7 microrna binding site polymorphism in kras predicts improved outcome in patients with Metastatic Colorectal Cancer treated with salvage cetuximab panitumumab monotherapy
Clinical Cancer Research, 2014Co-Authors: Heinzjosef Lenz, Zenia Saridaki, Joanne B Weidhaas, Pierre Laurentpuig, Bart Jacobs, Jef De Schutter, Wendy De Roock, David Salzman, Wu ZhangAbstract:Purpose: An inherited mutation in KRAS (LCS6-variant or rs61764370) results in altered control of the KRAS oncogene. We studied this biomarker9s correlation to anti-EGFR monoclonal antibody (mAb) therapy response in patients with Metastatic Colorectal Cancer. Experimental Design: LCS6-variant and KRAS/BRAF mutational status was determined in 512 patients with Metastatic Colorectal Cancer treated with salvage anti-EGFR mAb therapy, and findings correlated with outcome. Reporters were tested in colon Cancer cell lines to evaluate the differential response of the LCS6-variant allele to therapy exposure. Results: In this study, 21.2% (109 of 512) of patients with Metastatic Colorectal Cancer had the LCS6-variant (TG/GG), which was found twice as frequently in the BRAF -mutated versus the wild-type (WT) group ( P = 0.03). LCS6-variant patients had significantly longer progression- free survival (PFS) with anti-EGFR mAb monotherapy treatment in the whole cohort (16.85 vs. 7.85 weeks; P = 0.019) and in the double WT ( KRAS and BRAF ) patient population (18 vs. 10.4 weeks; P = 0.039). Combination therapy (mAbs plus chemotherapy) led to improved PFS and overall survival (OS) for nonvariant patients, and brought their outcome to levels comparable with LCS6-variant patients receiving anti-EGFR mAb monotherapy. Combination therapy did not lead to improved PFS or OS for LCS6-variant patients. Cell line studies confirmed a unique response of the LCS6-variant allele to both anti-EGFR mAb monotherapy and chemotherapy. Conclusions: LCS6-variant patients with Metastatic Colorectal Cancer have an excellent response to anti-EGFR mAb monotherapy, without any benefit from the addition of chemotherapy. These findings further confirm the importance of this mutation as a biomarker of anti-EGFR mAb response in patients with Metastatic Colorectal Cancer, and warrant further prospective confirmation. Clin Cancer Res; 20(17); 4499–510. ©2014 AACR .
Marwan Fakih - One of the best experts on this subject based on the ideXlab platform.
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trifluridine tipiracil plus bevacizumab for third line management of Metastatic Colorectal Cancer sunlight study design
Future Oncology, 2021Co-Authors: Josep Tabernero, Marwan Fakih, Fortunato Ciardiello, Nadia Amellal, Ronan Fougeray, Julien Taieb, Gerald W Prager, Catherine Leger, Eric Van CutsemAbstract:Trifluridine/tipiracil (FTD/TPI) is an orally active formulation of trifluridine, a thymidine-based nucleoside analog, and tipiracil hydrochloride, a thymidine phosphorylase inhibitor that increases the bioavailability of trifluridine. Preliminary studies of FTD/TPI plus bevacizumab have produced encouraging results in the treatment of refractory Metastatic Colorectal Cancer. Here, we describe the design of the multinational Phase III SUNLIGHT, an open-label study of FTD/TPI plus bevacizumab as third-line treatment for patients with unresectable Metastatic Colorectal Cancer. A total of 490 patients will be randomized 1:1 to receive either FTD/TPI plus bevacizumab, or FTD/TPI monotherapy. The primary objective is to significantly improve overall survival with FTD/TPI plus bevacizumab compared with FTD/TPI monotherapy. The first patient was enrolled in November 2020.
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pertuzumab plus trastuzumab for her2 amplified Metastatic Colorectal Cancer mypathway an updated report from a multicentre open label phase 2a multiple basket study
Lancet Oncology, 2019Co-Authors: Funda Mericbernstam, Howard A. Burris, Herbert Hurwitz, Marwan Fakih, Kanwal Pratap Singh Raghav, Robert R Mcwilliams, Ari M Vanderwalde, Charles Swanton, Razelle Kurzrock, Christopher SweeneyAbstract:Summary Background Therapies targeting HER2 have improved clinical outcomes in HER2-positive breast and gastric Cancers, and are emerging as potential treatments for HER2-positive Metastatic Colorectal Cancer. MyPathway evaluates the activity of targeted therapies in non-indicated tumour types with potentially predictive molecular alterations. We aimed to assess the activity of pertuzumab and trastuzumab in patients with HER2-amplified Metastatic Colorectal Cancer. Methods MyPathway is an ongoing, phase 2a, multiple basket study. Patients in this subset analysis were aged 18 years or older and had treatment-refractory, histologically confirmed HER2-amplified Metastatic Colorectal Cancer with measurable or evaluable disease and an Eastern Cooperative Oncology Group performance status score of 2 or less, enrolled from 25 hospitals or clinics in 16 states of the USA. Patients received pertuzumab (840 mg loading dose, then 420 mg every 3 weeks, intravenously) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg every 3 weeks, intravenously). The primary endpoint was the proportion of patients who achieved an objective response based on investigator-reported tumour responses. Analyses were done per protocol. This ongoing trial is registered with ClinicalTrials.gov , number NCT02091141 . Findings Between Oct 20, 2014, and June 22, 2017, 57 patients with HER2-amplified Metastatic Colorectal Cancer were enrolled in the MyPathway study and deemed eligible for inclusionin this cohort analysis. Among these 57 evaluable patients, as of Aug 1, 2017, one (2%) patient had a complete response and 17 (30%) had partial responses; thus overall 18 of 57 patients achieved an objective response (32%, 95% CI 20–45). The most common treatment-emergent adverse events were diarrhoea (19 [33%] of 57 patients), fatigue (18 [32%] patients), and nausea (17 [30%] patients). Grade 3–4 treatment-emergent adverse events were recorded in 21 (37%) of 57 patients, most commonly hypokalaemia and abdominal pain (each three [5%] patients). Serious treatment-emergent adverse events were reported in ten (18%) patients and two (4%) of these adverse events (ie, chills and infusion-related reaction) were considered treatment related. There were no treatment-related deaths. Interpretation Dual HER2-targeted therapy with pertuzumab plus trastuzumab is well tolerated and could represent a therapeutic opportunity for patients with heavily pretreated, HER2-amplified Metastatic Colorectal Cancer. Funding F Hoffmann-La Roche/Genentech.
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Metastatic Colorectal Cancer current state and future directions
Journal of Clinical Oncology, 2015Co-Authors: Marwan FakihAbstract:Substantial improvements have been made in the management of Metastatic Colorectal Cancer over the last two decades. The overall survival of patients diagnosed with unresectable Metastatic Colorectal Cancer has increased from approximately 1 year during the era of fluoropyrimidine monotherapy to more than 30 months with the integration of multiple cytotoxic agents and targeted therapies. More effective therapeutic combinations have increased the rate of curative-intent surgical resections, resulting in median survival in this subgroup that exceed 5 years. Here we review the landscape of systemic therapies for unresectable Metastatic Colorectal Cancer during the current era of targeted therapies, review the effects of RAS and BRAF mutations on clinical decision making, and reflect on future directions for the treatment of Metastatic Colorectal Cancer.
Chiara Cremolini - One of the best experts on this subject based on the ideXlab platform.
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initial therapy with folfoxiri and bevacizumab for Metastatic Colorectal Cancer
The New England Journal of Medicine, 2014Co-Authors: Fotios Loupakis, Lisa Salvatore, Chiara Cremolini, G Masi, Sara Lonardi, Vittorina Zagonel, Enrico Cortesi, Gianluca Tomasello, M Ronzoni, Rosella SpadiAbstract:BackgroundA fluoropyrimidine plus irinotecan or oxaliplatin, combined with bevacizumab (a monoclonal antibody against vascular endothelial growth factor), is standard first-line treatment for Metastatic Colorectal Cancer. Before the introduction of bevacizumab, chemotherapy with fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) showed superior efficacy as compared with fluorouracil, leucovorin, and irinotecan (FOLFIRI). In a phase 2 study, FOLFOXIRI plus bevacizumab showed promising activity and an acceptable rate of adverse effects. MethodsWe randomly assigned 508 patients with untreated Metastatic Colorectal Cancer to receive either FOLFIRI plus bevacizumab (control group) or FOLFOXIRI plus bevacizumab (experimental group). Up to 12 cycles of treatment were administered, followed by fluorouracil plus bevacizumab until disease progression. The primary end point was progression-free survival. ResultsThe median progression-free survival was 12.1 months in the experimental group, as compared...
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genetic modulation of the let 7 microrna binding to kras 3 untranslated region and survival of Metastatic Colorectal Cancer patients treated with salvage cetuximab irinotecan
Pharmacogenomics Journal, 2010Co-Authors: Francesco Graziano, Emanuele Canestrari, N Galluccio, Lisa Salvatore, Annamaria Ruzzo, Fotios Loupakis, D Santini, Marco B. L. Rocchi, Bruno Vincenzi, Chiara CremoliniAbstract:Genetic modulation of the Let-7 microRNA binding to KRAS 3′-untranslated region and survival of Metastatic Colorectal Cancer patients treated with salvage cetuximab–irinotecan
Eric Van Cutsem - One of the best experts on this subject based on the ideXlab platform.
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trifluridine tipiracil plus bevacizumab for third line management of Metastatic Colorectal Cancer sunlight study design
Future Oncology, 2021Co-Authors: Josep Tabernero, Marwan Fakih, Fortunato Ciardiello, Nadia Amellal, Ronan Fougeray, Julien Taieb, Gerald W Prager, Catherine Leger, Eric Van CutsemAbstract:Trifluridine/tipiracil (FTD/TPI) is an orally active formulation of trifluridine, a thymidine-based nucleoside analog, and tipiracil hydrochloride, a thymidine phosphorylase inhibitor that increases the bioavailability of trifluridine. Preliminary studies of FTD/TPI plus bevacizumab have produced encouraging results in the treatment of refractory Metastatic Colorectal Cancer. Here, we describe the design of the multinational Phase III SUNLIGHT, an open-label study of FTD/TPI plus bevacizumab as third-line treatment for patients with unresectable Metastatic Colorectal Cancer. A total of 490 patients will be randomized 1:1 to receive either FTD/TPI plus bevacizumab, or FTD/TPI monotherapy. The primary objective is to significantly improve overall survival with FTD/TPI plus bevacizumab compared with FTD/TPI monotherapy. The first patient was enrolled in November 2020.
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quality of life at baseline in the international open label early access program of trifluridine tipiracil in previously treated Metastatic Colorectal Cancer phase iiib
Journal of Clinical Oncology, 2018Co-Authors: Alfredo Falcone, Timothy J Price, Lucjan Wyrwicz, Martin Becquart, Julien Taieb, Jean Francois Seitz, Shanti Moreno, Nadjat Mounedji, Eric Van CutsemAbstract:803Background: Pivotal phase 3 RECOURSE trial evaluated efficacy and safety of trifluridine/tipiracil (FTD/TPI, also known TAS-102) in Metastatic Colorectal Cancer (mCRC) without collecting quality...
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continuation of bevacizumab after first progression in Metastatic Colorectal Cancer ml18147 a randomised phase 3 trial
Lancet Oncology, 2013Co-Authors: Jaafar Bennouna, Richard Greil, Eric Van Cutsem, J Sastre, Dirk Arnold, Pia Osterlund, Roger Von Moos, J M Vieitez, Olivier Bouche, Christophe BorgAbstract:Summary Background Bevacizumab plus fluoropyrimidine-based chemotherapy is standard treatment for first-line and bevacizumab-naive second-line Metastatic Colorectal Cancer. We assessed continued use of bevacizumab plus standard second-line chemotherapy in patients with Metastatic Colorectal Cancer progressing after standard first-line bevacizumab-based treatment. Methods In an open-label, phase 3 study in 220 centres in Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany, the Netherlands, Norway, Portugal, Saudi Arabia, Spain, Sweden, and Switzerland, patients (aged ≥18 years) with unresectable, histologically confirmed Metastatic Colorectal Cancer progressing up to 3 months after discontinuing first-line bevacizumab plus chemotherapy were randomly assigned in a 1:1 ratio to second-line chemotherapy with or without bevacizumab 2·5 mg/kg per week equivalent (either 5 mg/kg every 2 weeks or 7·5 mg/kg every 3 weeks, intravenously). The choice between oxaliplatin-based or irinotecan-based second-line chemotherapy depended on the first-line regimen (switch of chemotherapy). A combination of a permuted block design and the Pocock and Simon minimisation algorithm was used for the randomisation. The primary endpoint was overall survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00700102. Findings Between Feb 1, 2006, and June 9, 2010, 409 (50%) patients were assigned to bevacizumab plus chemotherapy and 411 (50%) to chemotherapy alone. Median follow-up was 11·1 months (IQR 6·4–15·6) in the bevacizumab plus chemotherapy group and 9·6 months (5·4–13·9) in the chemotherapy alone group. Median overall survival was 11·2 months (95% CI 10·4–12·2) for bevacizumab plus chemotherapy and 9·8 months (8·9–10·7) for chemotherapy alone (hazard ratio 0·81, 95% CI 0·69–0·94; unstratified log-rank test p=0·0062). Grade 3–5 bleeding or haemorrhage (eight [2%] vs one [ vs three [ vs 12 [3%]) were more common in the bevacizumab plus chemotherapy group than in the chemotherapy alone group. The most frequently reported grade 3–5 adverse events were neutropenia (65 [16%] in the bevacizumab and chemotherapy group vs 52 [13%] in the chemotherapy alone group), diarrhoea (40 [10%] vs 34 [8%], respectively), and asthenia (23 [6%] vs 17 [4%], respectively). Treatment-related deaths were reported for four patients in the bevacizumab plus chemotherapy group and three in the chemotherapy alone group. Interpretation Maintenance of VEGF inhibition with bevacizumab plus standard second-line chemotherapy beyond disease progression has clinical benefits in patients with Metastatic Colorectal Cancer. This approach is also being investigated in other tumour types, including Metastatic breast and non-small cell lung Cancers. Funding F Hoffmann-La Roche.
Fotios Loupakis - One of the best experts on this subject based on the ideXlab platform.
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initial therapy with folfoxiri and bevacizumab for Metastatic Colorectal Cancer
The New England Journal of Medicine, 2014Co-Authors: Fotios Loupakis, Lisa Salvatore, Chiara Cremolini, G Masi, Sara Lonardi, Vittorina Zagonel, Enrico Cortesi, Gianluca Tomasello, M Ronzoni, Rosella SpadiAbstract:BackgroundA fluoropyrimidine plus irinotecan or oxaliplatin, combined with bevacizumab (a monoclonal antibody against vascular endothelial growth factor), is standard first-line treatment for Metastatic Colorectal Cancer. Before the introduction of bevacizumab, chemotherapy with fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) showed superior efficacy as compared with fluorouracil, leucovorin, and irinotecan (FOLFIRI). In a phase 2 study, FOLFOXIRI plus bevacizumab showed promising activity and an acceptable rate of adverse effects. MethodsWe randomly assigned 508 patients with untreated Metastatic Colorectal Cancer to receive either FOLFIRI plus bevacizumab (control group) or FOLFOXIRI plus bevacizumab (experimental group). Up to 12 cycles of treatment were administered, followed by fluorouracil plus bevacizumab until disease progression. The primary end point was progression-free survival. ResultsThe median progression-free survival was 12.1 months in the experimental group, as compared...
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genetic modulation of the let 7 microrna binding to kras 3 untranslated region and survival of Metastatic Colorectal Cancer patients treated with salvage cetuximab irinotecan
Pharmacogenomics Journal, 2010Co-Authors: Francesco Graziano, Emanuele Canestrari, N Galluccio, Lisa Salvatore, Annamaria Ruzzo, Fotios Loupakis, D Santini, Marco B. L. Rocchi, Bruno Vincenzi, Chiara CremoliniAbstract:Genetic modulation of the Let-7 microRNA binding to KRAS 3′-untranslated region and survival of Metastatic Colorectal Cancer patients treated with salvage cetuximab–irinotecan
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treatment with 5 fluorouracil folinic acid oxaliplatin and irinotecan enables surgical resection of metastases in patients with initially unresectable Metastatic Colorectal Cancer
Annals of Surgical Oncology, 2006Co-Authors: G Masi, Fotios Loupakis, S Cupini, Lorenzo Marcucci, E Cerri, G Allegrini, I Brunetti, E Pfanner, Maurizio Viti, Orlando GolettiAbstract:Background The prognosis of unresectable Metastatic Colorectal Cancer might be improved if a radical surgical resection of metastases could be performed after a response to chemotherapy.
