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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Factors affecting recurrence and prognosis after R0 resection for colorectal cancer with peritoneal metastasis.
TL;DR: Harvesting of more than eight lymph nodes and administration of intense adjuvant chemotherapy after R0 surgery are recommended for greater prediction accuracy and improved prognosis.
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Isolated hepatic perfusion with oxaliplatin combined with 100 mg melphalan in patients with metastases confined to the liver: A phase I study
L.B.J. van Iersel,E.M. De Leede,A.L. Vahrmeijer,Fred G.J. Tijl,J. den Hartigh,Peter J. K. Kuppen,Henk H. Hartgrink,Hans Gelderblom,J.W.R. Nortier,R.A.E.M. Tollenaar,C.J.H. van de Velde +10 more
TL;DR: Applying this dose in IHP is not expected to improve treatment results in patients with isolated hepatic metastases, in view of similar and even higher doses of oxaliplatin applied in both systemic treatment and hepatic artery infusion.
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The role of cetuximab in the treatment of metastatic colorectal cancer.
Lubos Holubec,Vaclav Liska,Vit Martin Matejka,Ondrej Fiala,Jana Dreslerova,Petra Mrazkova,Vladislav Treska,Jindrich Finek +7 more
TL;DR: The role of cetuximab in treating metastatic colorectal cancer and wild type of the Kirsten rat sarcoma viral oncogene is discussed with a focus on the treatment of hepatic metastases.
Journal ArticleDOI
Effect of adjuvant chemotherapy after pulmonary metastasectomy on the prognosis of colorectal cancer.
Kazu Shiomi,Masanori Naito,Takeo Sato,Takatoshi Nakamura,Hiroyasu Nakashima,Masahito Naito,Masashi Mikubo,Yoshio Matsui,Masahiko Watanabe,Yukitoshi Satoh +9 more
TL;DR: Adjuvant chemotherapy after curative resection of lung metastases might strongly affect the prognosis of metastatic CRC patients and Narrowing of suitable candidates by predicting the effects of systemic chemotherapy and prospective randomized studies are needed.
Journal ArticleDOI
Regional and inter-hospital differences in the utilisation of liver surgery for patients with synchronous colorectal liver metastases in the Netherlands
Jorine 't Lam-Boer,E.P. van der Stok,Joost Huiskens,Rob H.A. Verhoeven,Cornelis J. A. Punt,Marloes A. G. Elferink,J.H.W. de Wilt,Cees Verhoef,Cees H. Dejong,Dirk J. Grünhagen,T.M. van Gulik,K.P. de Jong,Geert Kazemier,I. Q. Molenaar,T. Ruers +14 more
TL;DR: There is a large inter-hospital and inter-regional variation in the utilisation of liver resection and patients diagnosed with SCLM in expert centres had a higher chance of undergoing Liver resection.
References
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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.
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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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