Journal ArticleDOI
Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial.
Gunnar Folprecht,Thomas Gruenberger,Wolf O. Bechstein,Hans-Rudolf Raab,Florian Lordick,Jörg T. Hartmann,Hauke Lang,Andrea Frilling,Jan Stoehlmacher,Jürgen Weitz,Ralf Konopke,Christian Stroszczynski,Torsten Liersch,Detlev Ockert,Thomas Herrmann,Eray Goekkurt,Fabio Parisi,Claus-Henning Köhne +17 more
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In this paper, the effectiveness of cetuximab combined with chemotherapy in this setting was assessed, and the primary endpoint was tumour response assessed by Response Evaluation Criteria In Solid Tumours (RECIST), analysed by modified intention to treat.Abstract:
Summary Background Neoadjuvant chemotherapy for unresectable colorectal liver metastases can downsize tumours for curative resection. We assessed the effectiveness of cetuximab combined with chemotherapy in this setting. Methods Between Dec 2, 2004, and March 27, 2008, 114 patients were enrolled from 17 centres in Germany and Austria; three patients receiving FOLFOX6 alone were excluded from the analysis. Patients with non-resectable liver metastases (technically non-resectable or ≥5 metastases) were randomly assigned to receive cetuximab with either FOLFOX6 (oxaliplatin, fluorouracil, and folinic acid; group A) or FOLFIRI (irinotecan, fluorouracil, and folinic acid; group B). Randomisation was not blinded, and was stratified by technical resectability and number of metastases, use of PET staging, and EGFR expression status. They were assessed for response every 8 weeks by CT or MRI. A local multidisciplinary team reassessed resectability after 16 weeks, and then every 2 months up to 2 years. Patients with resectable disease were offered liver surgery within 4–6 weeks of the last treatment cycle. The primary endpoint was tumour response assessed by Response Evaluation Criteria In Solid Tumours (RECIST), analysed by modified intention to treat. A retrospective, blinded surgical review of patients with radiological images at both baseline and during treatment was done to assess objectively any changes in resectability. The study is registered with ClinicalTrials.gov, number NCT00153998. Findings 56 patients were randomly assigned to group A and 55 to group B. One patient in each group were excluded from the analysis of the primary endpoint because they discontinued treatment before first full dose, one patient in group B was excluded because of early pulmonary embolism. A confirmed partial or complete response was noted in 36 (68%) of 53 patients in group A, and 30 (57%) of 53 patients in group B (difference 11%, 95% CI −8 to 30; odds ratio [OR] 1·62, 0·74–3·59; p=0·23). The most frequent grade 3 and 4 toxicities were skin toxicity (15 of 54 patients in group A, and 22 of 55 patients in group B), and neutropenia (13 of 54 patients in group A and 12 of 55 patients in group B). R0 resection was done in 20 (38%) of 53 patients in group A and 16 (30%) of 53 of patients in group B. In a retrospective analysis of response by KRAS status, a partial or complete response was noted in 47 (70%) of 67 patients with KRAS wild-type tumours versus 11 (41%) of 27 patients with KRAS -mutated tumours (OR 3·42, 1·35–8·66; p=0·0080). According to the retrospective review, resectability rates increased from 32% (22 of 68 patients) at baseline to 60% (41 of 68) after chemotherapy (p Interpretation Chemotherapy with cetuximab yields high response rates compared with historical controls, and leads to significantly increased resectability. Funding Merck-Serono, Sanofi-Aventis, and Pfizer.read more
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Changes of T Cells and Cytokines TGF-β1 and IL-10 in Mice During Liver Metastasis of Colon Carcinoma: Implications for Liver Anti-tumor Immunity
Xiao-Ming Huang,Yifeng Zou,Lei Lian,Xiaojian Wu,Xiaosheng He,Xiaowen He,Xianrui Wu,Yan Huang,Ping Lan +8 more
TL;DR: Changes in the systemic and local immunological environment contribute to immunological escape mechanisms during liver metastasis of colon carcinoma, and therapies aiming at immune microenvironment may prove a useful strategy in the treatment of metastatic disease in the future.
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The importance of optimal drug sequencing in metastatic colorectal cancer: biological rationales for the observed survival benefit conferred by first-line treatment with EGFR inhibitors
TL;DR: Existing preclinical and clinical data suggest that a biological basis exists for providing RAS-wild-type patients with first-line EGFR inhibitors, followed by second-line VEGF inhibitors.
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Role of yttrium-90 selective internal radiation therapy in the treatment of liver-dominant metastatic colorectal cancer: an evidence-based expert consensus algorithm.
D. Rohan Jeyarajah,Maria B. Doyle,N. Joseph Espat,Paul D. Hansen,David A. Iannitti,Joseph Kim,Thavam Thambi-Pillai,Brendan C. Visser +7 more
TL;DR: What is known about the role of SIRT with Y-90 as neoadjuvant, definitive, or palliative therapy in these different clinical situations is reviewed and insight is provided into when treatment with SIRTWithY-90 may be appropriate and useful, organized into distinct treatment algorithm steps.
Journal Article
KRAS discordance between primary and metastatic tumor in patients with metastatic colorectal carcinoma.
Siyar Ekinci A,Umut Demirci,Cakmak Oksuzoglu B,Ozturk A,Onur Esbah,Tahsin Ozatli,Celik B,Burcin Budakoglu,Ibrahim Turker,Oznur Bal,Nedim Turan +10 more
TL;DR: This is the first study to evaluate KRAS discordance between primary and metastasis in CRC patients, who underwent metastasectomy, together with survival data and no survival difference was determined between patients with or without discordance.
Journal ArticleDOI
EGFR and β1-integrin targeting differentially affect colorectal carcinoma cell radiosensitivity and invasion.
Mandy Poschau,Mandy Poschau,Ellen Dickreuter,Ellen Dickreuter,Jenny Singh-Müller,Jenny Singh-Müller,Katja Zscheppang,Katja Zscheppang,Iris Eke,Iris Eke,Iris Eke,Torsten Liersch,Nils Cordes +12 more
TL;DR: The data show inefficiency of Cetuximab and AIIB2 on top of radiochemotherapy and the functions of KRAS and BRAF in therapy resistance remain unanswered and warrant further preclinical molecular-driven investigations.
References
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Journal ArticleDOI
New Guidelines to Evaluate the Response to Treatment in Solid Tumors
Patrick Therasse,Susan G. Arbuck,Elizabeth Eisenhauer,Jantien Wanders,Richard Kaplan,Larry Rubinstein,Jaap Verweij,Martine Van Glabbeke,Allan T. van Oosterom,Michaele C. Christian,S. Gwyther +10 more
TL;DR: A model by which a combined assessment of all existing lesions, characterized by target lesions and nontarget lesions, is used to extrapolate an overall response to treatment is proposed, which is largely validated by the Response Evaluation Criteria in Solid Tumors Group and integrated into the present guidelines.
Journal ArticleDOI
Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer
Herbert Hurwitz,Louis Fehrenbacher,William Novotny,Thomas Cartwright,John D. Hainsworth,W. Heim,Jordan Berlin,Ari David Baron,Susan Griffing,Eric Holmgren,Napoleone Ferrara,Gwen Fyfe,Beth Rogers,Robert W. Ross,Fairooz F. Kabbinavar +14 more
TL;DR: The addition of bevacizumab to fluorouracil-based combination chemotherapy results in statistically significant and clinically meaningful improvement in survival among patients with metastatic colorectal cancer.
Journal ArticleDOI
Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer.
David Cunningham,Yves Humblet,Salvatore Siena,David Khayat,Harry Bleiberg,Armando Santoro,D. Bets,M. Mueser,Andreas Harstrick,Chris Verslype,Ian Chau,Eric Van Cutsem +11 more
TL;DR: Cetuximab has clinically significant activity when given alone or in combination with irinotecan in patients with ir inotecans-refractory colorectal cancer.
Journal ArticleDOI
Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer.
Eric Van Cutsem,Claus Henning Köhne,Erika Hitre,J. Zaluski,Chung Rong Chang Chien,A. Makhson,Geert R. D'Haens,Tamás Pintér,Robert Lim,György Bodoky,Jae Kyung Roh,Gunnar Folprecht,Paul Ruff,Christopher Stroh,Sabine Tejpar,Michael Schlichting,Johannes Nippgen,Philippe Rougier +17 more
TL;DR: In this paper, the efficacy of cetuximab plus irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for metastatic colorectal cancer was investigated.
Journal ArticleDOI
Clinical Score for Predicting Recurrence After Hepatic Resection for Metastatic Colorectal Cancer: Analysis of 1001 Consecutive Cases
TL;DR: There is a need for clearly defined and widely applicable clinical criteria for the selection of patients who may benefit from hepatic resection for metastatic colorectal cancer and studies of preoperative staging techniques or of adjuvant therapies should consider using such a score for stratification of patients.
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