Phase II study of biweekly cetuximab in combination with irinotecan as second-line treatment in patients with platinum-resistant gastro-oesophageal cancer

Schønnemann, Katrine Rahbek; Yilmaz, Mette Karen; Bjerregaard, Jon Kroll; Nielsen, Karsten; Pfeiffer, Per

doi:10.1016/j.ejca.2011.12.005

Cited by 18 publications

(6 citation statements)

References 31 publications

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“…However, most patients are diagnosed with locally advanced tumors, regional lymph node involvement, or metastatic disease (14). Clinical trials have attempted to improve the clinical outcome by reducing the rate of local disease recurrence through integrating radiotherapy and chemotherapy in patients with ESCC, but a clear benefit has never been achieved (15,16). Thus, development of adequate screening techniques and effective novel therapeutic regimens are urgently needed.…”

Section: Discussionmentioning

confidence: 99%

Immuno-PET Imaging and Radioimmunotherapy of ⁶⁴Cu-/¹⁷⁷Lu-Labeled Anti-EGFR Antibody in Esophageal Squamous Cell Carcinoma Model

et al. 2016

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Immuno-PET provides valuable information about tumor location, phenotype, susceptibility to therapy, and treatment response, especially to targeted radioimmunotherapy. In this study, we prepared antiepidermal growth factor receptor (EGFR) antibody via identical chelator, 3,6,9,15-tetraazabicyclo[9.3.1]-pentadeca-1(15),11,13-trience-3,6,9,-triacetic acid (PCTA), labeled with 64 Cu or 177 Lu to evaluate the EGFR expression levels using immuno-PET and the feasibility of radioimmunotherapy in an esophageal squamous cell carcinoma (ESCC) model. Methods: Cetuximab was conjugated with p-SCN-Bn-PCTA and radiolabeled with 64 Cu or 177 Lu. In vitro EGFR expression levels were determined and compared using flow cytometry and cell binding assay. In vivo EGFR expression levels were evaluated via immuno-PET imaging of 64 Cu-cetuximab and biodistribution analysis. Micro-SPECT/CT imaging, biodistribution, and radioimmunotherapy studies of 177 Lu-cetuximab were performed in the ESCC model. Therapeutic responses were monitored using 18 F-FDG PET and immunohistochemical staining. Results: 64 Cu-or 177 Lu-labeled antibodies showed high radiolabeling yield (.98%), stability (.90%), and favorable immunoreactivity. In vitro EGFR status measured by cell binding assay was correlated with the flow cytometry data. Immuno-PET, micro-SPECT/CT, and biodistribution demonstrated specific uptake in ESCC tumors depending on the EGFR expression levels. Tumor accumulation of 64 Cu-and 177 Lu-cetuximab was peaked at 48 and 120 h, respectively. Radioimmunotherapy with 177 Lu-cetuximab showed significant inhibition of tumor growth (P , 0.01) and marked reduction of 18 F-FDG SUV compared with that of control (P , 0.05). Terminal deoxynucleotidyl transferase dUTP nick-end labeling positivity and Ki-67 staining indices increased and decreased, respectively, in the radioimmunotherapy group compared with other groups (P , 0.01). Conclusion: 64 Cu-cetuximab immuno-PET represented EGFR expression levels in ESCC tumors, and 177 Lu-cetuximab radioimmunotherapy effectively inhibited the tumor growth. The diagnostic and therapeutic convergence radiopharmaceutical 64 Cu-/ 177 Lu-PCTA-cetuximab may be useful as a diagnostic tool in patient selection and a potent radioimmunotherapy agent in EGFR-positive ESCC tumors.

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Section: Discussionmentioning

confidence: 99%

Immuno-PET Imaging and Radioimmunotherapy of ⁶⁴Cu-/¹⁷⁷Lu-Labeled Anti-EGFR Antibody in Esophageal Squamous Cell Carcinoma Model

et al. 2016

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“…In contrast, cetuximab in combination with cisplatin or irinotecan as a second line Dittmar Y et al . Individualized treatment of gastric cancer therapy revealed only a marginal benefit on the overall survival (7.1 mo) [17] . Moreover, cetuximab as a single agent administration for second line therapy resulted in even lower impact on the overall survival (3.6 to 4 mo) with poor response (9%) [18] .…”

Section: Growth Factors Growth Factor Receptors and Downstream Featuresmentioning

confidence: 99%

Individualized treatment of gastric cancer: Impact of molecular biology and pathohistological features

Dittmar

Settmacher

2015

WJGO

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Gastric cancer is one of the most common malignancies worldwide. The overall prognosis remains poor over the last decades even though improvements in surgical outcomes have been achieved. A better understanding of the molecular biology of gastric cancer and detection of eligible molecular targets might be of central interest to further improve clinical outcome. With this intention, first steps have been made in the research of growth factor signaling. Regarding morphogens, cell cycle and nuclear factor-κB signaling, a remarkable count of target-specific agents have been developed, nevertheless the transfer into the field of clinical routine is still at the beginning. The potential utility of epigenetic targets and the further evaluation of microRNA signaling seem to have potential for the development of novel treatment strategies in the future.

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“…Thirty-eight patients had mCRC [8,10] and 37 had esophageal or gastric cancer. [9] Sixty-three of these patients received at least 1 month of therapy with cetuximab, and were evaluable for intervention analysis. The median age was 63 years (range 41-77).…”

Section: Patient Populationmentioning

confidence: 99%

“…The median reported time to rash development was 10 days (95% CI [8][9][10][11][12][13][14]. Six patients (10%) did not develop any rash during the study period.…”

Section: Rashmentioning

confidence: 99%

“…Patients had GI cancer, and were unselected regarding age and gender. [8][9][10] In connection with the first out-patient visit for cetuximab therapy, patients were educated by the treating nurse on toxicity of cetuximab with special attention on skin toxicity including how and when to start tetracycline. In the pilot study, patients self-administered tetracycline at a dosage of 333 mg-1,000 mg daily for an indefinite period of time.…”

Section: Introductionmentioning

confidence: 99%

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Nursing interventions to minimize cetuximab-induced dermatologic toxicity

Larsen

Thode

Dieperink

et al. 2017

CNS

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Objective: This study investigated early nursing interventions with the purpose to minimize cetuximab-induced acneiform eruption. The most important side-effect of cetuximab is dermatologic toxicity, up to 90%. Dose-reduction or interruption of cetuximab reduces severity of dermatologic toxicity, probably at the cost of reduced efficacy of the cancer therapy. Thus, prevention or effective supportive care during treatment is important. The study evaluated if patient education could ensure compliance of cancer treatment and effect of oral tetracycline on acneiform eruption, with the purpose to minimize severity of dermatologic toxicity and reduce the use of tetracycline. Methods: The design was a single group prospective interventional study. Gastro-intestinal (GI) cancer patients treated with cetuximab between April 2009 and June 2011 were educated to start treatment with tetracycline 500 mg twice daily when acneiform eruption occurred. Patient's dermatologic toxicity were graded (by CTCAE) and registered by nurses. Results: Sixty-three patients were evaluable. Patients started tetracycline when acneiform eruption occurred. It reduced severity but not incidence of acneiform eruption, 10% of the patients never developed acneiform eruption and therefore never received tetracycline. Conclusions: Patient-education by a trained oncology nurse in the handling of cetuximab induced acneiform eruption is manageable and effective and ensures a high number of patients carrying through treatment with a full dose of cetuximab.

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Phase II study of biweekly cetuximab in combination with irinotecan as second-line treatment in patients with platinum-resistant gastro-oesophageal cancer

Cited by 18 publications

References 31 publications

Immuno-PET Imaging and Radioimmunotherapy of ⁶⁴Cu-/¹⁷⁷Lu-Labeled Anti-EGFR Antibody in Esophageal Squamous Cell Carcinoma Model

Immuno-PET Imaging and Radioimmunotherapy of ⁶⁴Cu-/¹⁷⁷Lu-Labeled Anti-EGFR Antibody in Esophageal Squamous Cell Carcinoma Model

Individualized treatment of gastric cancer: Impact of molecular biology and pathohistological features

Nursing interventions to minimize cetuximab-induced dermatologic toxicity

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Phase II study of biweekly cetuximab in combination with irinotecan as second-line treatment in patients with platinum-resistant gastro-oesophageal cancer

Cited by 18 publications

References 31 publications

Immuno-PET Imaging and Radioimmunotherapy of 64Cu-/177Lu-Labeled Anti-EGFR Antibody in Esophageal Squamous Cell Carcinoma Model

Immuno-PET Imaging and Radioimmunotherapy of 64Cu-/177Lu-Labeled Anti-EGFR Antibody in Esophageal Squamous Cell Carcinoma Model

Individualized treatment of gastric cancer: Impact of molecular biology and pathohistological features

Nursing interventions to minimize cetuximab-induced dermatologic toxicity

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Product

Resources

About

Immuno-PET Imaging and Radioimmunotherapy of ⁶⁴Cu-/¹⁷⁷Lu-Labeled Anti-EGFR Antibody in Esophageal Squamous Cell Carcinoma Model

Immuno-PET Imaging and Radioimmunotherapy of ⁶⁴Cu-/¹⁷⁷Lu-Labeled Anti-EGFR Antibody in Esophageal Squamous Cell Carcinoma Model