| Reference | 1. Clin Cancer Res. 2004 Jun 15;10(12 Pt 2):4238s-4240s.
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The role of erlotinib (Tarceva, OSI 774) in the treatment of non-small cell lung
cancer.
<br>
Perez-Soler R(1).
<br>
Author information: <br>
(1)Gutman Professor of Oncology, Montefiore Medical Center/Albert Einstein
College of Medicine, Bronx, New York, USA. [email protected]
<br>
Erlotinib (Tarceva) is a reversible and highly specific inhibitor of epidermal
growth factor receptor (EGFR) tyrosine kinase. Phase I studies established a
fixed daily oral dose of 150 mg as the recommended dose for Phase II studies.
Using this dose and schedule, the response rate in a group of 57 patients with
EGFR-positive non-small cell lung cancer after failure of platinum-containing
chemotherapy was 12%. The median survival was 8.4 months, and the 1-year survival
was 40%. Occurrence and severity of rash were correlated with an improved
survival independently of performance status. Another ongoing Phase II study in
50 patients with bronchoalveolar carcinoma has shown a response rate of 26%.
Results from two Phase III front-line studies in combination with chemotherapy,
TALENT and TRIBUTE, have been recently reported. The addition of erlotinib did
not improve response rate, time to progression, or survival. Efforts in the
continued development of erlotinib should be focused on the following: (a)
investigating the reasons for the lack of relationship between EGFR expression
and clinical outcome; (b) the reasons for the failure of the front-line
combination trials; and (c) confirming the rash/clinical outcome relationship.
Progress in these tasks will allow a better selection of patients who can benefit
from this therapy, permit the development of more effective combination schedules
with cytotoxics, and define whether this agent should be used at the optimal
biological dose or at the maximum-tolerated dose.
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2. Semin Oncol. 2003 Jun;30(3 Suppl 7):15-24.
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Preclinical studies with Erlotinib (Tarceva).
<br>
Akita RW(1), Sliwkowski MX.
<br>
Author information: <br>
(1)Department of Molecular Oncology, Genentech, Inc, South San Francisco, CA,
94080-4990, USA.
<br>
Erratum in<br>
Semin Oncol. 2003 Dec;30(6):826.
<br>
Erlotinib HCl (Tarceva; Genentech, Inc, South San Francisco, CA) is an orally
available, highly selective, reversible inhibitor of epidermal growth factor
receptor (HER1/EGFR) tyrosine kinase. Inhibition of tyrosine kinase activity
prevents HER1/EGFR phosphorylation, the associated downstream signaling events,
and may block tumorigenesis mediated by inappropriate HER1/EGFR signaling. In
vitro and in vivo studies show that erlotinib has activity against human
colorectal, head and neck, non-small cell lung, and pancreatic tumor cells.
Recent preclinical studies suggest that erlotinib may also have activity against
tumors that are dependent on HER2 activation for growth and/or survival.
Preclinical studies have addressed the feasibility of using erlotinib in
combination with various chemotherapeutic agents, radiotherapy, and targeted
agents. Combining agents that have different mechanisms of action has the
potential to improve efficacy and inhibit the development of resistance. For
example, in preclinical studies, combining erlotinib with cisplatin, doxorubicin,
gemcitabine, or low-dose paclitaxel has an additive effect on antitumor activity
with no increase in toxicity. Preclinical data provide a strong rationale for
investigating erlotinib in the clinical setting. However, additional studies are
required to gain further insights into the processes that regulate or influence
the antitumor activity of erlotinib.
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