The role of the epidermal growth factor receptor in the treatment of colorectal carcinoma

Waxman, Elizabeth S.; Herbst, Roy S.

doi:10.1053/sonu.2002.33072

Cited by 12 publications

(5 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most of the adverse events observed in patients treated with targeted biologic agents such as cetuximab are very different from and generally of less concern than those typically seen in patients treated with traditional chemotherapy regimens (Riddle, Lee, & Purdom, 2002;Waxman & Herbst, 2002). In comparison with the serious toxic effects of chemotherapy, which are well known and may include myelosuppression, febrile neutropenia, and nausea and vomiting, the overall safety profi le of cetuximab is favorable.…”

Section: Adverse Events Associated With Cetuximabmentioning

confidence: 91%

Cetuximab: Adverse Event Profi le and Recommendations for Toxicity Management

Thomas¹

2005

Clinical Journal of Oncology Nursing

View full text Add to dashboard Cite

Cetuximab (Erbitux, IMC-C225, ImClone Systems Incorporated, New York, NY) is a monoclonal antibody targeted to the epidermal growth factor receptor. Expression of the epidermal growth factor receptor is associated with disease progression, poor survival, poor response to therapy, and the development of resistance to therapy in many solid tumors. Cetuximab blocks the binding of natural ligands to the epidermal growth factor receptor, thus inhibiting oncogenic processes associated with its activation. Infusion reactions, acneform skin rash, and nail disorder are the most clinically relevant adverse events observed. Because infusion reactions can be life threatening when severe, nurses must administer prophylactic treatment with an H1 antagonist prior to infusion and actively manage cetuximab-related infusion reactions when they occur. Management of infusion reactions typically includes vigilant patient monitoring, appropriate medical supervision, readily available resources for the treatment of infusion reactions, and initiation of institution- or practice-specific protocols when necessary. Acneform skin rash is the most common adverse event, but severe (grade 3 or 4) rash requiring interruption of treatment is not common. Topical and systemic antibiotic therapies may be administered to reduce symptoms. Nail disorder typically is mild to moderate and is observed infrequently; this also may be treated with systemic and topical antibiotics. Overall, the safety profile of cetuximab is favorable compared to that typically seen with chemotherapeutic agents. The acneform skin rash and nail disorder, which may affect quality of life, rarely threaten the general well-being of patients and typically are manageable.

show abstract

Section: Adverse Events Associated With Cetuximabmentioning

confidence: 91%

Cetuximab: Adverse Event Profi le and Recommendations for Toxicity Management

Thomas¹

2005

Clinical Journal of Oncology Nursing

View full text Add to dashboard Cite

show abstract

“…Thousands of patients receive radiation therapy each year for either primary locally advanced rectal cancer, recurrent rectal cancer, or metastatic colorectal cancer, and the potential role of growth factor receptor inhibition in combination therapy has been reviewed (24). For example in one recent Phase II clinical trail, treatment with a combination of Cetuximab (C225) and Irinotecan produced a 67% response rate in colorectal carcinoma patients (25).…”

Section: Introductionmentioning

confidence: 99%

Radiosensitization by Pan ErbB Inhibitor CI-1033 in Vitro and in Vivo

Nyati¹,

Maheshwari²,

Hanasoge³

et al. 2004

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Overexpression of the ErbB family of receptor tyrosine kinases has been associated with uncontrolled growth of many tumor types and, therefore, presents a promising molecular target for cancer therapy. CI-1033 is a small molecule tyrosine kinase inhibitor that differs from other 4-anilinoquinazolines by being a pan ErbB (instead of epidermal growth factor receptor-specific) irreversible (instead of reversible) inhibitor. Therefore, we investigated the antitumor effect of CI-1033 alone and in combination with ionizing radiation in vitro and in vivo.Experimental Design: We selected three human colon carcinoma cell-lines (LoVo, Caco-2, which express activated epidermal growth factor receptor and ErbB-2 family members, and SW620, which does not), and analyzed the effects of CI-1033 both in vitro and in vivo. For in vivo studies LoVo and Caco-2 cells were implanted s.c. in the flank of nude mice. After the tumor reached ϳ100 mm 3 , treatment was initiated with 20 mg/kg of CI-1033 (orally once daily ؋ 5 for 3 successive weeks), radiation treatment (a total of 30 Gy given in 2 Gy once daily ؋ 5 for 3 successive weeks), or a combination of both CI-1033 and radiation treatment.Results: We found that exposure of LoVo and Caco-2, but not SW620 cells, to CI-1033 in the range of 1-3 M could inhibit constitutive signaling by tyrosine kinases, arrest cell growth, inhibit cells in G 1 , stimulate expression of p53, and induce apoptosis. The inhibition of cell growth by CI-1033 seemed to produce only minimal radiosensitization in LoVo and Caco-2 cells. In contrast, the combination of CI-1033 and radiation produced significant (P < 0.0005 and P ‫؍‬ 0.0002, respectively) and prolonged suppression of tumor growth in both the tumor types when compared with either treatment alone.Conclusions: These findings suggest that CI-1033 can increase the effectiveness of radiation therapy. The extent of suppression of tyrosine kinase activity by CI-1033, rather than the amount of activity in untreated cells, seemed to be more closely associated with the efficacy of combination treatment.

show abstract

“…This agent is indicated for the treatment of patients with metastatic breast cancer whose tumors overexpress the ErbB-2 (HER-2/neu) receptor [7,25,26]. Currently, many other ErbB receptor-targeted therapies are in development, including monoclonal antibodies and small molecules that target the tyrosine kinase domain of the receptors [10,17,[27][28][29][30]. Other compounds are being developed to target only the external domain of ErbB-1, such as cetuximab (Erbitux ® , IMC C-225; ImClone Systems, Inc.; New York, NY), EMD 72000 (Merck Kga; Darmstadt, Germany), ABX-EGF (Abgenix, Inc.; Fremont, CA), and MDX-447 (Medarex Inc.; Princeton, NJ).…”

Section: Erbb-targeted Therapeutics In Developmentmentioning

confidence: 99%

Signal Events: Cell Signal Transduction and Its Inhibition in Cancer

Rowinsky¹

2003

The Oncologist

View full text Add to dashboard Cite

Signal transduction refers to communication processes used by regulatory molecules to mediate the essential cell processes of growth, differentiation, and survival. Signal transduction elements interact through complex biochemically related networks. Aberrations in signal transduction elements can lead to increased proliferative potential, sustained angiogenesis, tissue invasion and metastasis, and apoptosis inhibition. Most human neoplasms have aberrant signal transduction elements. Several compounds that target aberrant signal transduction elements, such as those in the ErbB family of tyrosine kinase receptors and mammalian target of rapamycin, are in development. To date, commercially available signal-transduction-targeting compounds include trastuzumab, a monoclonal antibody against the ErbB-2 receptor for the treatment of metastatic breast cancer overexpressing the ErbB-2 (HER-2) receptor, and gefitinib, an inhibitor of the ErbB-1 receptor tyrosine kinase that recently received regulatory approval for the treatment of patients with non-small cell lung cancer. In contrast to traditional cytotoxic treatments, although signal transduction inhibitors are capable of inducing tumor regression, particularly in malignancies that are principally driven by specific target aberrations, preclinical and early clinical investigations suggest that their predominant beneficial effects are growth inhibitory in nature; therefore, new clinical trial designs and evaluation end points may be required to ultimately assess their value. Prospective profiling of patients and tumors to determine treatment response is also essential to the success of these clinical trials. However, responsiveness to these novel therapies is dependent on a multitude of factors that ultimately determine the robustness and quality of the downstream response.

show abstract

The role of the epidermal growth factor receptor in the treatment of colorectal carcinoma

Cited by 12 publications

References 30 publications

Cetuximab: Adverse Event Profi le and Recommendations for Toxicity Management

Cetuximab: Adverse Event Profi le and Recommendations for Toxicity Management

Radiosensitization by Pan ErbB Inhibitor CI-1033 in Vitro and in Vivo

Signal Events: Cell Signal Transduction and Its Inhibition in Cancer

Contact Info

Product

Resources

About