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Role of erlotinib in the management of pancreatic cancer.

Starling N, Neoptolemos J, Cunningham D - Ther Clin Risk Manag (2006)

Bottom Line: Despite the adoption of gemcitabine monotherapy as a standard of care, outcomes remain poor.The situation has changed with capecitabine and erlotinib, either of which in combination with gemcitabine produces a small increase in survival.A randomized phase III study in locally advanced and metastatic pancreatic cancer has shown a survival advantage for the combination of gemcitabine plus erlotinib over gemcitabine alone.

View Article: PubMed Central - PubMed

ABSTRACT
Pancreatic cancer is a largely chemo-resistant disease with a poor prognosis. Despite the adoption of gemcitabine monotherapy as a standard of care, outcomes remain poor. Until recently randomized phase III studies have not demonstrated superiority of various cytotoxic combinations or a number of the newer biologic targeted drugs. The situation has changed with capecitabine and erlotinib, either of which in combination with gemcitabine produces a small increase in survival. Erlotinib is a small molecule tyrosine kinase inhibitor against epidermal growth factor receptor which has an important role in the molecular pathogenesis of pancreatic cancer. In both pre-clinical and early clinical evaluation it has shown anti-tumor activity against pancreatic cancer in combination with gemcitabine. A randomized phase III study in locally advanced and metastatic pancreatic cancer has shown a survival advantage for the combination of gemcitabine plus erlotinib over gemcitabine alone. The rationale for the clinical development of erlotinib in combination with gemcitabine in pancreatic cancer culminating in this randomized trial, together with pharmacologic, toxicity and patient selection considerations form the focus of this review.

No MeSH data available.


Related in: MedlinePlus

Study schema for the AVITA randomized Phase III study.
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fig2: Study schema for the AVITA randomized Phase III study.

Mentions: Combination of erlotinib with an effective cytotoxic doublet such as gemcitabine plus capecitabine would appear to be an attractive therapeutic option. Furthermore combination of erlotinib with another biologic agent such as the anti-VEGF agent bevacizumab, also appears attractive. In colon and gastric cancer cell lines, combined blockade of EGFR and VEGF resulted in significant antitumor responses which were greater than suppression of one pathway alone (Ciardiello et al 2000; Jung et al 2002). In a phase I/II study in lung cancer, the combination of erlotinib and bevacizumab was tolerable, had no pharmacokinetic interaction and importantly resulted in responses in the absence of cytotoxic treatment (Herbst, Prager, et al 2005). Currently, there is an international placebo controlled phase III study underway comparing the combination of gemcitabine plus erlotinib according to the PA.3 schedule versus gemcitabine, erlotinib plus bevacizumab in patients with metastatic pancreatic cancer (Figure 2), the results of which should prove very interesting. The erlotinib dose being used is 100 mg/day and the study is powered to demonstrate a survival difference between the arms.


Role of erlotinib in the management of pancreatic cancer.

Starling N, Neoptolemos J, Cunningham D - Ther Clin Risk Manag (2006)

Study schema for the AVITA randomized Phase III study.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1936363&req=5

fig2: Study schema for the AVITA randomized Phase III study.
Mentions: Combination of erlotinib with an effective cytotoxic doublet such as gemcitabine plus capecitabine would appear to be an attractive therapeutic option. Furthermore combination of erlotinib with another biologic agent such as the anti-VEGF agent bevacizumab, also appears attractive. In colon and gastric cancer cell lines, combined blockade of EGFR and VEGF resulted in significant antitumor responses which were greater than suppression of one pathway alone (Ciardiello et al 2000; Jung et al 2002). In a phase I/II study in lung cancer, the combination of erlotinib and bevacizumab was tolerable, had no pharmacokinetic interaction and importantly resulted in responses in the absence of cytotoxic treatment (Herbst, Prager, et al 2005). Currently, there is an international placebo controlled phase III study underway comparing the combination of gemcitabine plus erlotinib according to the PA.3 schedule versus gemcitabine, erlotinib plus bevacizumab in patients with metastatic pancreatic cancer (Figure 2), the results of which should prove very interesting. The erlotinib dose being used is 100 mg/day and the study is powered to demonstrate a survival difference between the arms.

Bottom Line: Despite the adoption of gemcitabine monotherapy as a standard of care, outcomes remain poor.The situation has changed with capecitabine and erlotinib, either of which in combination with gemcitabine produces a small increase in survival.A randomized phase III study in locally advanced and metastatic pancreatic cancer has shown a survival advantage for the combination of gemcitabine plus erlotinib over gemcitabine alone.

View Article: PubMed Central - PubMed

ABSTRACT
Pancreatic cancer is a largely chemo-resistant disease with a poor prognosis. Despite the adoption of gemcitabine monotherapy as a standard of care, outcomes remain poor. Until recently randomized phase III studies have not demonstrated superiority of various cytotoxic combinations or a number of the newer biologic targeted drugs. The situation has changed with capecitabine and erlotinib, either of which in combination with gemcitabine produces a small increase in survival. Erlotinib is a small molecule tyrosine kinase inhibitor against epidermal growth factor receptor which has an important role in the molecular pathogenesis of pancreatic cancer. In both pre-clinical and early clinical evaluation it has shown anti-tumor activity against pancreatic cancer in combination with gemcitabine. A randomized phase III study in locally advanced and metastatic pancreatic cancer has shown a survival advantage for the combination of gemcitabine plus erlotinib over gemcitabine alone. The rationale for the clinical development of erlotinib in combination with gemcitabine in pancreatic cancer culminating in this randomized trial, together with pharmacologic, toxicity and patient selection considerations form the focus of this review.

No MeSH data available.


Related in: MedlinePlus