Randomized Phase II Trial of Cetuximab, Bevacizumab, and Irinotecan Compared With Cetuximab and Bevacizumab Alone in Irinotecan-Refractory Colorectal Cancer: The BOND-2 Study

Saltz, Leonard B.; Lenz, Heinz‐Josef; Kindler, Hedy L.; Hochster, Howard S.; Wadler, Scott; Hoff, Paulo M.; Kemeny, Nancy E.; Hollywood, Ellen; Gönen, Mithat; Quinones, M.; Morse, Michael J.; Chen, Alice

doi:10.1200/jco.2007.12.0949

Cited by 383 publications

(206 citation statements)

References 8 publications

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“…After irinotecan failure, this combination increased the response rate and prolonged the time to progression (response rate was 37% vs 23% and median time to progression 7.9 months vs 5.6 months). 12 The combination therapy with cetuximab after the failure of the conventional therapy increases resectability rates without increasing operative mortality or liver injury. Adam and colleagues showed that 7% of patients treated with cetuximab after the failure of the conventional therapy experienced a treatment response that allowed curative hepatectomy.…”

Section: Metastatic Colorectal Cancer (Crc)mentioning

confidence: 99%

Management of cutaneous side effects of cetuximab therapy with vitamin K1 crème

Ocvirk¹,

Reberšek²

2008

Radiology and Oncology

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Section: Metastatic Colorectal Cancer (Crc)mentioning

confidence: 99%

Management of cutaneous side effects of cetuximab therapy with vitamin K1 crème

Ocvirk¹,

Reberšek²

2008

Radiology and Oncology

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“…13 Early preclinical and clinical studies have suggested that blocking both angiogenesis and EGFR may enhance therapeutic efficacy. [14][15][16][17][18][19] Moreover, cetuximab in combination with chemotherapy improves survival of patients with colorectal cancer. 20,21 Therefore, the combination of chemotherapy with anti-EGFR antibodies has been studied in Phase III clinical trials.…”

mentioning

confidence: 99%

Bevacizumab reduces tumor targeting of antiepidermal growth factor and anti‐insulin‐like growth factor 1 receptor antibodies

Heskamp

Boerman

Molkenboer-Kuenen

et al. 2013

Intl Journal of Cancer

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Bevacizumab (antivascular endothelial growth factor [anti‐VEGF]) and cetuximab (antiepidermal growth factor receptor [anti‐EGFR]) are approved antibodies for treatment of cancer. However, in advanced colorectal cancer, the combination fails to improve survival. As the reason for the lack of activity is unknown, our study aims to determine the effect of bevacizumab on targeting of anti‐EGFR and insulin‐like growth factor 1 receptor (IGF‐1R) antibodies in tumors with single‐photon emission computed tomography (SPECT)/CT imaging. Mice with subcutaneous EGFR and IGF‐1R‐expressing SUM149 xenografts received a single dose of bevacizumab (10 mg/kg) or saline. After 4 days, mice were injected with radiolabeled cetuximab or R1507, an anti‐IGF‐1R antibody. A control group received a radiolabeled irrelevant IgG (hLL2). Three days later, SPECT/CT images were acquired and mice were dissected to determine the concentration of antibodies in the tissues. Tumors were analyzed immunohistochemically to determine vascular density (CD34), VEGF, EGFR and IGF‐1R expression. SPECT/CT imaging revealed that bevacizumab treatment significantly reduced tumor targeting of radiolabeled cetuximab by 40% from 33.1 ± 1.1 %ID/g to 19.8 ± 5.7 %ID/g (p = 0.009) for untreated and bevacizumab‐treated tumors, respectively. A similar effect was found for 111In‐R1507: tumor targeting of R1507 decreased by 35%. No significant differences in tumor uptake were observed in mice that received an irrelevant IgG. Uptake in normal organs was not altered by bevacizumab. Immunohistochemical analysis showed that vascular density decreased with 43%, whereas EGFR and IGF‐1R expression was unaltered. In conclusion, bevacizumab treatment significantly reduces tumor targeting of anti‐EGFR and anti‐IGF‐1R antibodies. This emphasizes the importance of timing and sequencing of bevacizumab in combination with other antibodies.

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“…90 Several clinical studies are ongoing to evaluate the combination of cetuximab with bevacizumab (anti-VEGF Mab) after the encouraging preliminary results of Saltz et al 91 Another approach involves the association of cetuximab with small molecule tyrosine kinase inhibitors (TKIs) such as erlotinib, 92 gefitinib 93 and lapatinib. 94 …”

Section: Resultsmentioning

confidence: 99%

Understanding and circumventing resistance to anticancer monoclonal antibodies

Reslan

Dalle

Dumontet

2009

mAbs

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With the widespread use of therapeutic monoclonal antibodies in the treatment of patients with cancer, resistance to these agents has become a major issue. Preclinical models of drug action or resistance have contributed to unravel the main mechanisms of resistance, involving both tumor-associated and host related factors. However our understanding of how a monoclonal antibody destroys cancer cells in a patient and why it one day stops being effective are still far from being complete. This review focuses on the available data on mechanisms of action and resistance to rituximab and includes some additional information for other monoclonal antibodies. Innovative approaches designed to overcome resistance, such as combination immunotherapy, costimulation with cytokines or growth factors are presented.

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Randomized Phase II Trial of Cetuximab, Bevacizumab, and Irinotecan Compared With Cetuximab and Bevacizumab Alone in Irinotecan-Refractory Colorectal Cancer: The BOND-2 Study

Cited by 383 publications

References 8 publications

Management of cutaneous side effects of cetuximab therapy with vitamin K1 crème

Management of cutaneous side effects of cetuximab therapy with vitamin K1 crème

Bevacizumab reduces tumor targeting of antiepidermal growth factor and anti‐insulin‐like growth factor 1 receptor antibodies

Understanding and circumventing resistance to anticancer monoclonal antibodies

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