Predictive Factors for Outcome in a Phase II Study of Gefitinib in Second-Line Treatment of Advanced Esophageal Cancer Patients

Janmaat, Maarten L.; Gallegos-Ruiz, M. I.; Rodriguez, José Antonio; Meijer, Gerrit A.; Vervenne, Walter L.; Richel, Dick J.; Groeningen, C. Van; Giaccone, Giuseppe

doi:10.1200/jco.2005.03.4900

Cited by 190 publications

(165 citation statements)

References 25 publications

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“…In an abstract presented at the American Society of Clinical Oncology 2004 Annual Meeting, Ferry et al [49] reported on a phase II trial of gefitinib in advanced adenocarcinoma of the esophagus, revealing that gefitinib is an active treatment with a disease control rate (PR or SD) of 58%. Recently, Janmaat et al [50] published the results of a phase II trial in which gefitinib was given to advanced esophageal cancer patients. Unfortunately, gefitinib had only limited antitumor activity.…”

Section: The Role Of Egfr In Esophageal Cancermentioning

confidence: 99%

Activation of Growth Factor Receptors in Esophageal Cancer—Implications for Therapy

et al. 2007

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Esophageal cancer is a highly aggressive disease and is the seventh most common cause of cancer-related death in the western world. Worldwide, it ranks as the sixth most frequent cause of cancer death. Despite advances in surgical techniques and treatment, the prognosis of esophageal cancer remains poor, with very few longterm survivors. The need for novel strategies to detect esophageal cancer earlier and to improve current therapy is urgent.It is well established that growth factors and growth factor receptor-mediated signaling pathways are important components of the transformation process in many forms of cancer, including esophageal cancer. With the recent advances in drug development, there are emerging possibilities to use growth factor signal transduction pathways in targeted therapy. This review provides a summary of the role of growth factors and their receptors in esophageal cancer and discusses their potential roles as biomarkers and as targets in therapy.

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Section: The Role Of Egfr In Esophageal Cancermentioning

confidence: 99%

Activation of Growth Factor Receptors in Esophageal Cancer—Implications for Therapy

et al. 2007

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“…Several phase I and II studies of EGFR tyrosine kinase inhibitors as immunotherapy in previously treated OG cancers have been reported with response rates ranging from 2.85 to 12% (Ferry et al, 2004;Van Groeningen and Giaccone, 2004;Janmaat et al, 2006). A phase II study of cetuximab combined with FOLFIRI in untreated gastric and OGJ cancers achieved an ORR of 44.1% (95% CI 27.5-60.9%) (Pinto et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…A phase II study of cetuximab combined with FOLFIRI in untreated gastric and OGJ cancers achieved an ORR of 44.1% (95% CI 27.5-60.9%) (Pinto et al, 2007). Janmaat et al (2006) identified female gender, squamous histology and high EGFR expression to be associated with improved outcome following the administration of gefitinib in patients with advanced OG cancer. A study of erlotinib demonstrated activity in OGJ tumours but no objective responses in gastric cancers (Dragovich et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Phase I study of epirubicin, cisplatin and capecitabine plus matuzumab in previously untreated patients with advanced oesophagogastric cancer

Starling

Cunningham

et al. 2008

Br J Cancer

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To evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of the humanised antiepidermal growth factor receptor monoclonal antibody matuzumab combined with epirubicin, cisplatin and capecitabine (ECX) in patients as first-line treatment for advanced oesophagogastric cancer that express epidermal growth factor receptor (EGFR). This was a phase I dose escalation study of matuzumab at 400 and 800 mg weekly and 1200 mg every 3 weeks combined with ECX (epirubicin 50 mg m À2 , cisplatin 60 mg m À2 on day 1 and capecitabine 1000 mg m À2 daily). Patients were treated until disease progression, unacceptable toxicity or for a maximum of eight cycles. Twenty-one patients were treated with matuzumab at three different dose levels (DLs) combined with ECX. The main dose-limiting toxicity (DLT) was grade 3 lethargy at 1200 mg matuzumab every 3 weeks and thus 800 mg matuzumab weekly was the maximum-tolerated dose (MTD). Other common toxicities included rash, nausea, stomatitis and diarrhoea. Pharmacokinetic evaluation demonstrated that the coadministration of ECX did not alter the exposure of matuzumab. Pharmacodynamic studies on skin biopsies demonstrated inhibition of the EGFR pathway. Objective response rates of 65% (95% confidence interval (CI): 43 -82), disease stabilisation of 25% (95% CI: 11 -47) and a disease control rate (CR þ PR þ SD) of 90% were achieved overall. The MTD of matuzumab in combination with ECX was 800 mg weekly, and at this DL it was well-tolerated and showed encouraging antitumour activity. At the doses evaluated in serial skin biopsies, matuzumab decreased phosphorylation of EGFR and MAPK, and increased phosphorylation of STAT-3.

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“…Several studies have attempted to define the response rate and clinical outcomes of a treatment of using gefitinib in esophageal carcinoma patients. In 2006, Janmaat et al performed a phase II of 36 patients who had failed one line of prior chemotherapy and were treated with gefitinib (500 mg/ day) (38). In this study, gefitinib showed a modest activity in second-line treatment of advanced esophageal carcinoma.…”

Section: Gefitinibmentioning

confidence: 98%

“…However, not all studies have confirmed this result. Janmaat et al investigated 36 patients with advanced esophageal cancer treated with gefitinib (38) and no EGFR mutation was observed.…”

Section: Egfr Mutation In Esophageal Carcinomamentioning

confidence: 99%

Role of epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of esophageal carcinoma and the suggested mechanisms of action

Sheng

Mao

2012

Oncology Letters

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Abstract. Cumulative evidence indicates that epidermal growth factor receptor (EGFR) is one of the most commonly altered genes in human cancer, via overexpression, amplification and mutation. Targeted inhibition of EGFR activity suppresses signal transduction pathways which control tumor cell growth, proliferation and resistance to apoptosis. Small molecule tyrosine kinase inhibitors (TKIs) are among the most common EGFR-targeting agents and have been used clinically to treat various malignancies. This review discusses the mechanism of action and clinical data that are relevant to the use of EGFR-TKIs in the treatment of esophageal carcinoma. The clinical and basic scientific experience of these agents thus far have implications for the future of therapeutic targeting of EGFR.

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Predictive Factors for Outcome in a Phase II Study of Gefitinib in Second-Line Treatment of Advanced Esophageal Cancer Patients

Cited by 190 publications

References 25 publications

Activation of Growth Factor Receptors in Esophageal Cancer—Implications for Therapy

Activation of Growth Factor Receptors in Esophageal Cancer—Implications for Therapy

Phase I study of epirubicin, cisplatin and capecitabine plus matuzumab in previously untreated patients with advanced oesophagogastric cancer

Role of epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of esophageal carcinoma and the suggested mechanisms of action

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