Phase II study of erlotinib in patients with malignant pleural mesothelioma: a Southwest Oncology Group Study.

Phase II study of erlotinib in patients with malignant pleural mesothelioma: a Southwest Oncology Group Study. Research Abstract Details 

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Phase II study of erlotinib in patients with malignant pleural mesothelioma: a Southwest Oncology Group Study. Abstract Text:

Linda L Garland,Cathryn Rankin,David R Gandara,Saul E Rivkin,Katherine M Scott,Raymond B Nagle,Andres J P Klein-Szanto,Joseph R Testa,Deborah A Altomare,Ernest C Borden,

PURPOSE: Malignant pleural mesothelioma (MPM) expresses high levels of epidermal growth factor receptor (EGFR), and preclinical studies have identified antitumor activity of EGFR tyrosine kinase inhibitors (TKIs) in MPM. We conducted a phase II trial of the EGFR TKI erlotinib in previously untreated patients with MPM. PATIENTS AND METHODS: Patients with measurable and nonmeasurable disease were treated with erlotinib 150 mg/d on days 1 through 28 of each 28-day dosing cycle. Archived patient tumors were analyzed for immunohistochemical expression of EGFR, phospho-EGFR, human epidermal growth factor receptor 2 (HER2), phospho-extracellular signal-regulated kinase (ERK), and phosphatase and tensin homolog (PTEN) and phosphorylation of members of the phosphatidylinositol 3-kinase/Akt signaling pathway. RESULTS: Sixty-three patients were treated on the study. EGFR was highly expressed in 75% of patient tumors, as was phospho-ERK (82%), phospho-Akt (84%), phospho-mammalian target of rapamycin (74%), and phospho-forkhead (74%). HER2 was rarely expressed, and loss of PTEN was rare. For 33 patients with measurable disease, there were no objective responses; 14 patients (42%) had stable disease, 15 patients (45%) had disease progression, and four patients had inadequate assessments to determine response. Toxicities were mainly constitutional (51%), dermatologic (82%), and GI (52%); there was one death on trial, which was related to dyspnea. Median overall survival time was 10 months; 1-year survival rate was 43%; and median progression-free survival time was 2 months. CONCLUSION: Single-agent erlotinib was not effective in MPM, despite high expression of EGFR. Activation of the ERK and phosphatidylinositol 3-kinase/Akt downstream pathways are possible resistance mechanisms to EGFR TKI. The activated phosphatidylinositol 3-kinase/Akt pathway is a potential therapeutic target for MPM.

Phase II study of erlotinib in patients with malignant pleural mesothelioma: a Southwest Oncology Group Study. Publishing Authors By Initials

LL Garland,C Rankin,DR Gandara,SE Rivkin,KM Scott,RB Nagle,AJ Klein-Szanto,JR Testa,DA Altomare,EC Borden,

For similar diagnosis: prognosis: treatment outcome research abstracts see: diagnosis: prognosis: treatment outcome research

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Phase II study of erlotinib in patients with malignant pleural mesothelioma: a Southwest Oncology Group Study. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of clinical oncology : official journal of

VOLUME: 25

Page Numbers: 2406-13

Journal Abbreviation: J. Clin. Oncol.

ISSN: 1527-7755

DAY: 10

MONTH: Jun

YEAR: 2007

Phase II study of erlotinib in patients with malignant pleural mesothelioma: a Southwest Oncology Group Study. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8309333

Phase II study of erlotinib in patients with malignant pleural mesothelioma: a Southwest Oncology Group Study. Keywords Mesh Terms:

KEYWORDS: Treatment Outcome

MESH TERMS: metabolism

Chemical & Substance for Abstract: Phase II study of erlotinib in patients with malignant pleural mesothelioma: a Southwest Oncology Group Study. Information

Substance Name: Proto-Oncogene Proteins c-akt

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Phase II study of erlotinib in patients with malignant pleural mesothelioma: a Southwest Oncology Group Study.

AFFILIATION: University of Arizona Cancer Center, Tucson, AZ, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA76462

ACRONYM: CA

MEDLINETA: J Clin Oncol

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