Cetuximab in Combination With Capecitabine, Irinotecan, and Radiotherapy for Patients With Locally Advanced Rectal Cancer: Results of a Phase II MARGIT Trial

Horisberger, Karoline; Treschl, Anne; Mai, Sabine; Miranda, Manuel Barreto; Kienle, Peter; Ströbel, Philipp; Erben, Philipp; Woernle, Christoph M.; Dinter, Dietmar; Kähler, Georg; Hochhaus, Andreas; Post, Stefan; Willeke, Frank; Wenz, Frederik; Hofheinz, Ralf–Dieter

doi:10.1016/j.ijrobp.2008.10.014

Cited by 104 publications

(53 citation statements)

References 34 publications

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“…21 The addition of a second chemotherapeutic agent to neoadjuvant capecitabine-based CRT with cetuximab has not demonstrated a marked improvement to the rates of pCR or tumor downstaging in LARC, 24 which remain similar to those reported from studies of neoadjuvant capecitabine-based CRT, 12,13,25 or capecitabine-based CRT with irinotecan or oxaliplatin. 26,27 In the present study an assessment of radiological tumor response according to RECIST criteria was made.…”

Section: Neoadjuvant Cetuximab Plus Crt On Tumor Response In Larcmentioning

confidence: 59%

A phase II study of cetuximab, capecitabine and radiotherapy in neoadjuvant treatment of patients with locally advanced resectable rectal cancer

Velenik

Ocvirk

Oblak

et al. 2010

European Journal of Surgical Oncology (EJSO)

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Please cite this article as: Velenik V, Ocvirk J, Oblak I, Anderluh F. A phase II study of cetuximab, capecitabine and radiotherapy in neoadjuvant treatment of patients with locally advanced resectable rectal cancer, European Journal of Surgical Oncology (2009Oncology ( ), doi: 10.1016Oncology ( /j.ejso.2009 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. M A N U S C R I P T A C C E P T E D ARTICLE IN PRESS

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Section: Neoadjuvant Cetuximab Plus Crt On Tumor Response In Larcmentioning

confidence: 59%

A phase II study of cetuximab, capecitabine and radiotherapy in neoadjuvant treatment of patients with locally advanced resectable rectal cancer

Velenik

Ocvirk

Oblak

et al. 2010

European Journal of Surgical Oncology (EJSO)

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“…Recent phase II trials evaluating the effect of cetuximab in the neoadjuvant therapy of locally advanced rectal cancer revealed disappointing results in terms of histopathologic responses as an early endpoint (8)(9)(10). In fact, the rate of complete histopathologic response ranged only between 5% and 10%.…”

Section: Discussionmentioning

confidence: 99%

“…These data prompted the initiation of phase I/II trials to evaluate the effect of cetuximab in the neoadjuvant therapy of locally advanced rectal cancer (7)(8)(9)(10). Unexpectedly, the results of these trials were disappointing.…”

Section: Introductionmentioning

confidence: 99%

Biomarkers for Cetuximab-Based Neoadjuvant Radiochemotherapy in Locally Advanced Rectal Cancer

Grimminger

Danenberg

Dellas

et al. 2011

Clinical Cancer Research

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Purpose: Phase II trials in locally advanced rectal cancer have shown that cetuximab-based neoadjuvant radiochemotherapy is feasible but without an improvement in complete pathologic response rates. Our goal was to identify patients who would benefit from cetuximab-based neoadjuvant chemoradiation measuring gene expression levels of proteins involved in tumor growth [endothelial growth factor receptor (EGFR)], angiogenesis [VEGF, VEGF receptors 1 and 2 (VEGFR1, VEGFR2)], DNA repair [excision repair cross-complementing 1 (ERCC1)], and drug metabolism [thymidylate synthetase (TS)]. We also determined mutation status of KRAS and BRAF.Experimental Design: This study was carried out on 130 patients with locally advanced rectal cancer who were enrolled in 4 different phase II clinical trials, using cetuximab-based chemoradiation. Tumor tissues were obtained before neoadjuvant and at surgical therapy. After microdissection, intratumoral gene expression levels and KRAS/BRAF mutation status were analyzed.Results: A significant decrease of TS, VEGFR1, and VEGFR2 gene expression was seen following neoadjuvant therapy (P < 0.03). High pretreatment VEGF gene expression levels were associated with nonresponse (P ¼ 0.070). KRAS mutations were found in 42% and mutant KRAS (KRAS mt) was significantly associated with pathologic nonresponse (P ¼ 0.037). In patients with wild-type KRAS (KRAS wt), low EGFR was significantly associated with higher nonresponse and VEGF mRNA expressions were associated with complete pathologic response (P ¼ 0.012; P ¼ 0.06). KRAS transversion (KRAS tv) was associated with tumor regression: nonresponse was more common in patients with KRAS tv than with KRAS wt (P ¼ 0.007). BRAF V600E mutations were not detected in any of the patients.Conclusion: This study suggests that pretreatment intratumoral EGFR and VEGF mRNA expression levels as well as KRAS mutation status are predictive markers of pathologic response to neoadjuvant cetuximabbased chemoradiation in locally advanced rectal cancer. Clin Cancer Res; 17(10); 3469-77. Ó2011 AACR.

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“…In the first study cetuximab was added to capecitabine (825 mg/m 2 twice daily, 5 days a week), irinotecan (40 mg/m 2 , days 1, 8, 15, 22 and 29), and RT (50.4 Gy in 28 fractions) in 10 patients, with pCR obtained in 2 (20%) patients [22]. In the MARGIT study, 50 patients received cetuximab in combination with capecitabine (500 mg/m 2 twice daily continuously), irinotecan (40 mg/m 2 weekly), and RT (50.4 Gy in 28 fractions), with a pCR in 4 (8%) patients [23].…”

Section: Cetuximabmentioning

confidence: 99%

The contribution of targeted therapy to the neoadjuvant chemoradiation of rectal cancer

Torino

Sarmiento

Gasparini

2013

Critical Reviews in Oncology/Hematology

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Cetuximab in Combination With Capecitabine, Irinotecan, and Radiotherapy for Patients With Locally Advanced Rectal Cancer: Results of a Phase II MARGIT Trial

Cited by 104 publications

References 34 publications

A phase II study of cetuximab, capecitabine and radiotherapy in neoadjuvant treatment of patients with locally advanced resectable rectal cancer

A phase II study of cetuximab, capecitabine and radiotherapy in neoadjuvant treatment of patients with locally advanced resectable rectal cancer

Biomarkers for Cetuximab-Based Neoadjuvant Radiochemotherapy in Locally Advanced Rectal Cancer

The contribution of targeted therapy to the neoadjuvant chemoradiation of rectal cancer

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