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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TLDR
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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SMAD4 gene mutation predicts poor prognosis in patients undergoing resection for colorectal liver metastases.
Takashi Mizuno,Jordan M. Cloyd,Diego Vicente,Kiyohiko Omichi,Yun Shin Chun,Scott Kopetz,Dipen M. Maru,Claudius Conrad,Ching Wei D. Tzeng,Steven H. Wei,Thomas A. Aloia,Jean Nicolas Vauthey +11 more
TL;DR: SMAD4 mutation is independently associated with worse outcomes among patients undergoing resection of CLM, and was an independent predictor for worse OS.
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An update on chemotherapy of colorectal liver metastases.
Chen Chen Wang,Jin Li +1 more
TL;DR: In this article, the authors demonstrated that active preoperative chemotherapy could achieve shrinkage of liver metastasis and thus render some for resection, and an increase in tumor resection rate and prolonged survival time among patients with colorectal liver metastases.
Journal ArticleDOI
Radioembolization and systemic chemotherapy improves response and survival for unresectable colorectal liver metastases.
TL;DR: Yttrium-90 microsphere radioembolization is safe and may best be combined with systemic chemotherapy for patients with unresectable colorectal liver metastases, and combined modality therapy appears to improve tumor response rates.
Journal ArticleDOI
Recommendations on management of EGFR inhibitor-induced skin toxicity: a systematic review.
J. M. Baas,L. L. Krens,Henk-Jan Guchelaar,Jan Ouwerkerk,F.A. de Jong,A.P.M. Lavrijsen,Hans Gelderblom +6 more
TL;DR: This work reviews and discusses available trials and case studies reporting on the management of EGFR inhibitor-induced skin toxicity and generates evidence based guidelines on its management.
Journal ArticleDOI
Repeat hepatic resection for colorectal liver metastases
R. Adair,Alastair L. Young,Andrew J. Cockbain,Deep J. Malde,K.R. Prasad,J.P.A. Lodge,Giles J. Toogood +6 more
TL;DR: The outcomes of repeat liver resection for the treatment of recurrent colorectal metastases confined to the liver are examined.
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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