Effect of gefitinib ('Iressa', ZD1839) on brain metastases in patients with advanced non-small-cell lung cancer

Katsuyuki Hotta, Katsuyuki Kiura, Hiroshi Ueoka, Masahiro Tabata, Keiichi Fujiwara, Toshiyuki Kozuki, Toshiaki Okada, Akiko Hisamoto, Mitsune Tanimoto

Research output: Contribution to journalArticle

155 Citations (Scopus)

Abstract

Background: Gefitinib ('Iressa', ZD1839), an orally active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (EGFR-TKI), has shown antitumor activity in refractory patients with non-small-cell lung cancer (NSCLC) in clinical trials. We have retrospectively analyzed the efficacy and tolerability of gefitinib in patients with advanced NSCLC treated at Okayama University Hospital. Methods: We reviewed the clinical records of 57 patients with advanced NSCLC who had received 250 mg/day gefitinib at our hospital between November 2000 and May 2003. Correlations between the sensitivity of brain metastases and extracranial disease following treatment with gefitinib were also investigated. Results: Extracranial objective responses were observed in 15 (27%; 95% confidence interval 15.8-40.3%) patients. Fourteen out of 57 patients had brain metastases; six experienced objective responses (one complete response, CR and five partial responses, PR) and eight had stable disease (SD) in the brain. Seven out of 14 patients with brain metastases experienced objective responses in their extracranial tumors and, interestingly, objective responses in the brain were observed in six (86%) of these patients. Multivariate analysis found that advanced age (≥70 years) and the presence of brain metastases were associated with clinical response to gefitinib (P = 0.01 and 0.05, respectively), and that female patients were more likely to respond. Median survival and median duration of response were 9.1 and 7.7 months, respectively. The majority of adverse events (AEs) were mild and reversible skin and gastrointestinal disorders, with grade 3 adverse events observed in six (11%) patients. Conclusions: This retrospective analysis has found that gefitinib is effective and well tolerated in patients with refractory NSCLC, confirming previous phase II trial data. Interestingly, gefitinib appeared to be effective for brain metastases as well as extracranial tumors. Further prospective trials are warranted to evaluate the efficacy of gefitinib in elderly patients and in patients with brain metastases.

Original languageEnglish
Pages (from-to)255-261
Number of pages7
JournalLung Cancer
Volume46
Issue number2
DOIs
Publication statusPublished - Nov 2004

Fingerprint

Non-Small Cell Lung Carcinoma
Neoplasm Metastasis
Brain
gefitinib
Brain Diseases
Epidermal Growth Factor Receptor
Protein-Tyrosine Kinases
Neoplasms
Multivariate Analysis
Clinical Trials
Confidence Intervals
Skin
Survival

Keywords

  • Brain metastasis
  • Extracranial disease
  • Gefitinib
  • Non-small-cell lung cancer
  • Prior chemotherapy
  • Skin reaction

ASJC Scopus subject areas

  • Oncology

Cite this

Effect of gefitinib ('Iressa', ZD1839) on brain metastases in patients with advanced non-small-cell lung cancer. / Hotta, Katsuyuki; Kiura, Katsuyuki; Ueoka, Hiroshi; Tabata, Masahiro; Fujiwara, Keiichi; Kozuki, Toshiyuki; Okada, Toshiaki; Hisamoto, Akiko; Tanimoto, Mitsune.

In: Lung Cancer, Vol. 46, No. 2, 11.2004, p. 255-261.

Research output: Contribution to journalArticle

Hotta, Katsuyuki ; Kiura, Katsuyuki ; Ueoka, Hiroshi ; Tabata, Masahiro ; Fujiwara, Keiichi ; Kozuki, Toshiyuki ; Okada, Toshiaki ; Hisamoto, Akiko ; Tanimoto, Mitsune. / Effect of gefitinib ('Iressa', ZD1839) on brain metastases in patients with advanced non-small-cell lung cancer. In: Lung Cancer. 2004 ; Vol. 46, No. 2. pp. 255-261.
@article{1b32393bb5a14d749eec23a9d6b60423,
title = "Effect of gefitinib ('Iressa', ZD1839) on brain metastases in patients with advanced non-small-cell lung cancer",
abstract = "Background: Gefitinib ('Iressa', ZD1839), an orally active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (EGFR-TKI), has shown antitumor activity in refractory patients with non-small-cell lung cancer (NSCLC) in clinical trials. We have retrospectively analyzed the efficacy and tolerability of gefitinib in patients with advanced NSCLC treated at Okayama University Hospital. Methods: We reviewed the clinical records of 57 patients with advanced NSCLC who had received 250 mg/day gefitinib at our hospital between November 2000 and May 2003. Correlations between the sensitivity of brain metastases and extracranial disease following treatment with gefitinib were also investigated. Results: Extracranial objective responses were observed in 15 (27{\%}; 95{\%} confidence interval 15.8-40.3{\%}) patients. Fourteen out of 57 patients had brain metastases; six experienced objective responses (one complete response, CR and five partial responses, PR) and eight had stable disease (SD) in the brain. Seven out of 14 patients with brain metastases experienced objective responses in their extracranial tumors and, interestingly, objective responses in the brain were observed in six (86{\%}) of these patients. Multivariate analysis found that advanced age (≥70 years) and the presence of brain metastases were associated with clinical response to gefitinib (P = 0.01 and 0.05, respectively), and that female patients were more likely to respond. Median survival and median duration of response were 9.1 and 7.7 months, respectively. The majority of adverse events (AEs) were mild and reversible skin and gastrointestinal disorders, with grade 3 adverse events observed in six (11{\%}) patients. Conclusions: This retrospective analysis has found that gefitinib is effective and well tolerated in patients with refractory NSCLC, confirming previous phase II trial data. Interestingly, gefitinib appeared to be effective for brain metastases as well as extracranial tumors. Further prospective trials are warranted to evaluate the efficacy of gefitinib in elderly patients and in patients with brain metastases.",
keywords = "Brain metastasis, Extracranial disease, Gefitinib, Non-small-cell lung cancer, Prior chemotherapy, Skin reaction",
author = "Katsuyuki Hotta and Katsuyuki Kiura and Hiroshi Ueoka and Masahiro Tabata and Keiichi Fujiwara and Toshiyuki Kozuki and Toshiaki Okada and Akiko Hisamoto and Mitsune Tanimoto",
year = "2004",
month = "11",
doi = "10.1016/j.lungcan.2004.04.036",
language = "English",
volume = "46",
pages = "255--261",
journal = "Lung Cancer",
issn = "0169-5002",
publisher = "Elsevier Ireland Ltd",
number = "2",

}

TY - JOUR

T1 - Effect of gefitinib ('Iressa', ZD1839) on brain metastases in patients with advanced non-small-cell lung cancer

AU - Hotta, Katsuyuki

AU - Kiura, Katsuyuki

AU - Ueoka, Hiroshi

AU - Tabata, Masahiro

AU - Fujiwara, Keiichi

AU - Kozuki, Toshiyuki

AU - Okada, Toshiaki

AU - Hisamoto, Akiko

AU - Tanimoto, Mitsune

PY - 2004/11

Y1 - 2004/11

N2 - Background: Gefitinib ('Iressa', ZD1839), an orally active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (EGFR-TKI), has shown antitumor activity in refractory patients with non-small-cell lung cancer (NSCLC) in clinical trials. We have retrospectively analyzed the efficacy and tolerability of gefitinib in patients with advanced NSCLC treated at Okayama University Hospital. Methods: We reviewed the clinical records of 57 patients with advanced NSCLC who had received 250 mg/day gefitinib at our hospital between November 2000 and May 2003. Correlations between the sensitivity of brain metastases and extracranial disease following treatment with gefitinib were also investigated. Results: Extracranial objective responses were observed in 15 (27%; 95% confidence interval 15.8-40.3%) patients. Fourteen out of 57 patients had brain metastases; six experienced objective responses (one complete response, CR and five partial responses, PR) and eight had stable disease (SD) in the brain. Seven out of 14 patients with brain metastases experienced objective responses in their extracranial tumors and, interestingly, objective responses in the brain were observed in six (86%) of these patients. Multivariate analysis found that advanced age (≥70 years) and the presence of brain metastases were associated with clinical response to gefitinib (P = 0.01 and 0.05, respectively), and that female patients were more likely to respond. Median survival and median duration of response were 9.1 and 7.7 months, respectively. The majority of adverse events (AEs) were mild and reversible skin and gastrointestinal disorders, with grade 3 adverse events observed in six (11%) patients. Conclusions: This retrospective analysis has found that gefitinib is effective and well tolerated in patients with refractory NSCLC, confirming previous phase II trial data. Interestingly, gefitinib appeared to be effective for brain metastases as well as extracranial tumors. Further prospective trials are warranted to evaluate the efficacy of gefitinib in elderly patients and in patients with brain metastases.

AB - Background: Gefitinib ('Iressa', ZD1839), an orally active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (EGFR-TKI), has shown antitumor activity in refractory patients with non-small-cell lung cancer (NSCLC) in clinical trials. We have retrospectively analyzed the efficacy and tolerability of gefitinib in patients with advanced NSCLC treated at Okayama University Hospital. Methods: We reviewed the clinical records of 57 patients with advanced NSCLC who had received 250 mg/day gefitinib at our hospital between November 2000 and May 2003. Correlations between the sensitivity of brain metastases and extracranial disease following treatment with gefitinib were also investigated. Results: Extracranial objective responses were observed in 15 (27%; 95% confidence interval 15.8-40.3%) patients. Fourteen out of 57 patients had brain metastases; six experienced objective responses (one complete response, CR and five partial responses, PR) and eight had stable disease (SD) in the brain. Seven out of 14 patients with brain metastases experienced objective responses in their extracranial tumors and, interestingly, objective responses in the brain were observed in six (86%) of these patients. Multivariate analysis found that advanced age (≥70 years) and the presence of brain metastases were associated with clinical response to gefitinib (P = 0.01 and 0.05, respectively), and that female patients were more likely to respond. Median survival and median duration of response were 9.1 and 7.7 months, respectively. The majority of adverse events (AEs) were mild and reversible skin and gastrointestinal disorders, with grade 3 adverse events observed in six (11%) patients. Conclusions: This retrospective analysis has found that gefitinib is effective and well tolerated in patients with refractory NSCLC, confirming previous phase II trial data. Interestingly, gefitinib appeared to be effective for brain metastases as well as extracranial tumors. Further prospective trials are warranted to evaluate the efficacy of gefitinib in elderly patients and in patients with brain metastases.

KW - Brain metastasis

KW - Extracranial disease

KW - Gefitinib

KW - Non-small-cell lung cancer

KW - Prior chemotherapy

KW - Skin reaction

UR - http://www.scopus.com/inward/record.url?scp=4944226682&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4944226682&partnerID=8YFLogxK

U2 - 10.1016/j.lungcan.2004.04.036

DO - 10.1016/j.lungcan.2004.04.036

M3 - Article

C2 - 15474674

AN - SCOPUS:4944226682

VL - 46

SP - 255

EP - 261

JO - Lung Cancer

JF - Lung Cancer

SN - 0169-5002

IS - 2

ER -