A dose-escalation phase I trial of nimotuzumab, an antibody against the epidermal growth factor receptor, in patients with advanced solid malignancies

You, Benoît; Brade, Anthony; Magalhaes, Joao; Siu, Lillian L.; Oza, Amit M.; Lovell, Sonya; Wang, Lisa; Hedley, David W.; Nicacio, Leonardo; Chen, Eric X.

doi:10.1007/s10637-010-9444-0

Cited by 23 publications

(18 citation statements)

References 30 publications

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“…No Grade 3 toxicity was observed, and the most severe adverse events were Grade 2 tremors and hypertension [11]. Both dose escalation trials revealed that h-R3 alone could be safely administered up to at least 400 mg per week, and no correlation were found between h-R3 dosage and toxicities [10,11].…”

Section: Discussionmentioning

confidence: 97%

“…In a clinical phase I trial, h-R3 alone could safely be administered up to highest planned dose level at 800 mg per week, although DLT was observed at 100 mg (Grade 3 fatigue) in one patient [10]. Other Grade 3 of h-R3-related adverse events were anemia (1/17 patient) and activated partial thromboplastin time prolongation (1/17 patient).…”

Section: Discussionmentioning

confidence: 99%

“…And no locoregional progression was found. The median survival time was 9.8 months (4.8-18) and time to progression was 9.8 months (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). OS were 78% and 67%, and LPFS, 100% and 100% at 6-months and 1-year, respectively (Fig.…”

Section: Treatment Efficacymentioning

confidence: 96%

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A phase I dose escalation study of Nimotuzumab in combination with concurrent chemoradiation for patients with locally advanced squamous cell carcinoma of esophagus

Zhao

et al. 2011

Invest New Drugs

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Nimotuzumab (h-R3) is a humanized anti-epidermal growth factor receptor monoclonal antibody. We conducted a phase I study to assess the safety, tolerance, maximal tolerance dose (MTD) and efficacy of h-R3 in combination with concurrent chemoradiation in patient with locally advanced esophageal carcinoma. Patients with locally advanced squamous cell carcinoma of esophagus were eligible. A total dose of 61.2 Gy was delivered by conventional fractionation. Chemotherapy was concurrently administered with irradiation every 4 weeks with PF regimen (cis-platinum of 25 mg/m(2)/d, d1-3; 5-Fu of 1,800 mg/m(2), intravenously infusion in 72 h) for 4 cycles. h-R3 was administrated weekly during irradiation for 6 weeks. h-R3 dose escalation started with 100 mg/week, and followed by 200 mg/week and 400 mg/week. Three patients were enrolled in of each dose cohort. 11 patients were enrolled in the trial with 3, 4 and 4 in 100 mg/week, 200 mg/week and 400 mg/week cohort, respectively. 2 patients in 200 mg/week and 400 mg/week cohort were withdrawn due to patients' own decisions. No dose limiting toxicity was observed. Grade 3-4 of esophagitis, Grade 3 of leucocytopenia and neutrocytopenia occurred in 18% (2/11), 18% (2/11) and 9% (1/11) of patients, respectively. For nimotuzumab-related toxicity only one patient experienced Grade 1 skin rash, and no Grade ≥ 3 of toxicity was noticed. In 9 patients, who completed planned treatments, 6-month and 1-year overall survival were 78% and 67%, respectively, and 1 year local progression-free survival, 100%. h-R3 of 400 mg/week administered concurrently with chemoradiation was well-tolerant. MTD has not been reached yet.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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A phase I dose escalation study of Nimotuzumab in combination with concurrent chemoradiation for patients with locally advanced squamous cell carcinoma of esophagus

Zhao

et al. 2011

Invest New Drugs

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“…20 EGFR expression was also evaluated immunohistochemically in ten NSCLC specimens in a Phase I trial of nimotuzumab plus palliative radiation therapy, but again there was no statistically significant association between EGFR expression and treatment response or outcome because of the limited sample size. 30 No definitive conclusions can thus be drawn at this time concerning the predictive utility of immunohistochemically determined EGFR expression level for the treatment of NSCLC patients with anti-EGFR mAbs, and further studies are therefore warranted.…”

Section: Predictive Biomarkers Molecular Predictors Of Responsementioning

confidence: 97%

“…Another Phase I trial was performed to assess the pharmacodynamic effects of escalating weekly intravenous doses of nimotuzumab ranging from 100 to 800 mg administered alone in Caucasian patients with advanced solid cancer. 30 Tumor and skin biopsy specimens were collected before and 3 weeks after the onset of treatment for immunohistochemical assessment of the expression of EGFR and its downstream signaling molecules. Seventeen patients were enrolled, including one who was not treated with nimotuzumab; most of the patients had colon (n = 11) or rectal (n = 2) cancer.…”

Section: Preclinical Datamentioning

confidence: 99%

Nimotuzumab, a novel monoclonal antibody to the epidermal growth factor receptor, in the treatment of non-small cell lung cancer

Takeda¹,

Okamoto²,

Nishimura³

et al. 2011

LCTT

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Abstract:The epidermal growth factor receptor (EGFR) is a promising therapeutic target in non-small cell lung cancer, and several therapeutic agents that target this receptor, including EGFR tyrosine kinase inhibitors and monoclonal antibodies to EGFR, have been developed. Such monoclonal antibodies have shown efficacy in combination with chemotherapy and radiotherapy. Nimotuzumab (h-R3) is a humanized monoclonal antibody to EGFR, and its effects in combination with radiation have been sufficiently promising to warrant further investigation in several types of cancer. Furthermore, the typical severe dermatologic toxicities associated with other monoclonal antibodies to EGFR have not been observed with nimotuzumab. We here summarize the results of preclinical studies as well as of previous and ongoing clinical trials of nimotuzumab for the treatment of non-small cell lung cancer.

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Dermatologic Complications of Cancer Chemotherapy

Patel,

Duvic

2017

Holland‐Frei Cancer Medicine

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Overview Dermatologic complications of cancer chemotherapy have become increasingly significant, especially with the continued development of new targeted antineoplastic agents. The frequency of mucocutaneous complications in cancer chemotherapy is often a reflection of the increased proliferative nature of affected tissues, such as the mucous membranes, skin, hair, and nails, which renders them particularly susceptible to the actions of chemotherapeutic drugs. This chapter reviews the specific side effects associated with targeted therapies and the more classic side effects of cytotoxic chemotherapies and their associated drugs.

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A dose-escalation phase I trial of nimotuzumab, an antibody against the epidermal growth factor receptor, in patients with advanced solid malignancies

Abstract: Nimotuzumab could be safety administered up to 800 mg with manageable toxicity. No relationships were found between pharmacodynamic effects on EGFR downstream signaling pathways and drug efficacy or toxicity.

Cited by 23 publications

References 30 publications

A phase I dose escalation study of Nimotuzumab in combination with concurrent chemoradiation for patients with locally advanced squamous cell carcinoma of esophagus

A phase I dose escalation study of Nimotuzumab in combination with concurrent chemoradiation for patients with locally advanced squamous cell carcinoma of esophagus

Nimotuzumab, a novel monoclonal antibody to the epidermal growth factor receptor, in the treatment of non-small cell lung cancer

Dermatologic Complications of Cancer Chemotherapy

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