Annals of Oncology 19: 2039–2042, 2008
Published online 21 July 2008
Phase II study of erlotinib as a salvage treatment for
non-small-cell lung cancer patients after failure of
D. H. Lee, S.-W. Kim, C. Suh*, D. H. Yoon, E. J. Yi & J.-S. Lee
Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
Received 14 May 2008; revised 11 June 2008; accepted 12 June 2008
Background: Both gefitinib and erlotinib are reversible epidermal growth factor receptor tyrosine kinase inhibitors,
but they have somewhat different pharmacological properties. We conducted a phase II study of erlotinib after failure
of gefitinib treatment in patients with non-small-cell lung cancer (NSCLC).
Patients and methods: Patients with advanced/metastatic NSCLC who had shown disease progression on
gefitinib treatment were treated with erlotinib 150 mg/day until disease progression or intolerable toxicity.
Results: Between September 2006 and January 2008, a total of 23 patients were enrolled and all were assessable
for response and toxicity. All patients were never smokers and all but one had adenocarcinoma. Of these 23 patients,
one had a partial response and one stable disease, resulting in an objective response rate of 4.3% and a disease
control rate of 8.7%. These two patients benefited from erlotinib for 6.2 months and 7.8 months, respectively; both
had also benefited from prior gefitinib therapy. The most common toxic effects were skin rash and diarrhea.
Conclusion: Erlotinib should not be given routinely after failure of gefitinib treatment, but can be an option for more
highly selected subsets, especially those who had benefited from prior gefitinib treatment. Identification of molecular
markers in tumors is important to understand and overcome acquired resistance to gefitinib.
Key words: erlotinib, gefitinib, non-small cell lung cancer
Erlotinib and gefitinib are oral epidermal growth factor
receptor (EGFR) tyrosine kinase inhibitors (TKIs) widely used
to treat patients with advanced or metastatic non-small-cell
lung cancer (NSCLC). Although their similar structures and
mechanism of action suggest that erlotinib and gefitinib should
have similar efficacies, the agents have somewhat different
pharmacological properties. For example, erlotinib is less
susceptible than is gefitinib to metabolism by the cytochrome
P450 pathway and therefore has a lower clearance rate and
inhibits the activity of wild-type EGFR at lower concentrations
than gefitinib [1, 2]. In addition, because the maximum-
tolerated doses of gefitinib and erlotinib are 1000 and 150 mg,
respectively [3, 4], the usual dose of erlotinib 150 mg may be
a higher biological dose than the usual dose of gefitinib 250 mg.
These differences may account at least in part for the
contradictory results of the two phase III studies, in which
erlotinib, but not gefitinib, was found to prolong survival in
previously treated patients [5, 6]. These findings suggested that
salvage treatment with erlotinib may be an option for patients
who fail gefitinib treatment. We therefore carried out
a prospective phase II study of erlotinib in patients with
advanced or metastatic NSCLC who showed disease
progression on gefitinib treatment.
patients and methods
Patients with advanced or metastatic NSCLC who had documented
progressive disease on gefitinib treatment were eligible for inclusion if they
had at least one unidimensionally measurable lesion, an Eastern
Cooperative Oncology Group performance status of zero to three, and
adequate organ functions [white blood cell 3000/ll, platelets 100 000/ll,
hemoglobin 9.0 g/dl, serum creatinine 1.5· the upper limit of normal
(ULN), bilirubin 1.25· ULN, and serum aminotransferases 2.5· ULN].
Prior chemotherapy or radiotherapy was allowed. Brain metastases were
also allowed if they were asymptomatic or controlled by supportive care.
However, those patients with unresolved chronic toxicity from prior
therapy, other active malignancies, uncontrolled brain metastases, or
severe comorbid conditions were excluded. The study was approved by
the institutional review board of the Asan Medical Center, and written
informed consent was obtained from all enrolled patients. The study was
carried out in accordance with the Declaration of Helsinki and Good
Clinical Practice guidelines.
This was an open-label, single-institution, phase II study. Patients received
erlotinib 150 mg once daily. One dose reduction per patient was permitted
*Correspondence to: Dr C. Suh, Department of Oncology, University of Ulsan College of
Medicine, Asan Medical Center, 388-1 Pungnap-2 dong, Songpa-gu, Seoul 138-736,
South Korea. Tel: +82-2-3010-3209, Fax: +82-2-3010-6961; E-mail: email@example.com
ª The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
All rights reserved. For permissions, please email: firstname.lastname@example.org