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Effect of gefitinib (ZD1839) on metastatic brain tumour
Lung Cancer (2004) 43, 371—372
LETTER TO THE EDITOR
Effect of gefitinib (ZD1839) on metastatic brain tumour Fujiwara et al. described the case of a patient with advanced adenocarcinoma of the lung, in whom treatment, once-daily with 250 mg gefitinib demonstrated a marked anti-tumour effect, published in the April 2003 issue of Lung Cancer (pages 73–76) [1]. Gefitinib, a selective oral epidermal growth factor receptor- tyrosine kinase inhibitor, is expected as an important new therapy for chemotherapy-resistant non-small-cell lung cancer (NSCLC) [2–5]. However, little is known about the long-term effect of gefitinib on the metastatic lesions in the brain [1,6]. We present a patient with chemotherapy-resistant NSCLC who had multiple brain metastases prior to therapy with gefitinib, which produced a drastic but transient clinical response. A 56-year-old woman with advanced adenocarcinoma of the lung was admitted to hospital with
severe headache and dyspnoea in July 2002. She had previously received two different chemotherapy regimens (cisplatin, mitomycin and vinorelbine for 1 month, and gemcitabine and docetaxel for 4 months). She had had a partial response, but the disease progressed for 2 months after the final chemotherapy. On admission, she suffered from breathlessness and analysis of the bloodgas revealed hypoxaemia and hypocarbia, during breathing in air (PaO2 , 56 mm Hg and PaCO2 , 32 mm Hg, at pH 7.48). A contrasting computed tomography (CT) scan showed multiple brain metastases (arrows in Fig. 1A) and chest X-rays revealed diffuse pulmonary involvement. She started to receive an oral administration of gefitinib at 250 mg once daily. After 3 weeks of treatment, she noted a reduction in headaches and dyspnoea, and a follow-up examination showed complete resolution of the cerebral metastatic lesions by contrasted CT scan (Fig. 1B) as well as the diffuse pulmonary involvement on chest X-rays. A repeated analysis of bloodgas
Fig. 1 Contrasted CT scan of the brain shows multiple nodular lesions before gefitinib treatment (arrows in A). Multiple nodular lesions have completely resolved after 3 weeks of treatment with gefitinib (B). 0169-5002/$ – see front matter © 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.lungcan.2003.09.017
372 revealed normal values and she was discharged with the same dose of gefitinib in September 2002. However, the brain tumours recurred despite the maintenance therapy with gefitinib in April 2003. Finally, she died of brain metastases in June 2003, whereas the pulmonary primary lesions remained stable. The present case suggests that gefitinib may have a marked anti-tumour activity in the brain in some advanced NSCLC patients with brain metastases but the effect may be transient. Metastatic lesions from NSCLC may gain refractoriness to this agent more rapidly than primary lesions, but more clinical documentation is needed.
References [1] Fujiwara K, Kiura K, Ueoka H, et al. Dramatic effect of ZD1839 (‘Iressa’) in a patient with advanced non-small-cell lung cancer and poor performance status. Lung Cancer 2003;40:73—6. [2] Pallis AG, Mavroudis D, Androulakis N, et al. ZD1839, a novel, oral epidermal growth factor receptor-tyrosine kinase inhibitor, as salvage treatment in patients with advanced non-small cell lung cancer. Experience from a single center participating in a compassionate use program. Lung Cancer 2003;40:301—7.
Letter to the Editor [3] Lichtner RB, Menrad A, Sommer A, et al. Signaling-inactive epidermal growth factor receptor/ligand complexes in intact carcinoma cells by quinazoline tyrosine kinase inhibitors. Cancer Res 2001;61:5790—5. [4] Ranson M, Hammond LA, Ferry D, et al. ZD 1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors: results of a phase I trial. J Clin Oncol 2002;20:2240—50. [5] Sridhar SS, Seymour L, Shepherd FA. Inhibitors of epidermalgrowth -factor receptors: a review of clinical research with a focus on non-small-cell lung cancer. Lancet Oncol 2003;4:397—406. [6] Villano JL, Mauer AM, Vokes EE. A case study documenting the anticancer activity of ZD1839 (Iressa) in the brain. Ann Oncol 2003;14:656—8.
Hidenori Takahashi Takashi Ohrui Satoru Ebihara Mitsuhiro Yamada Hidetada Sasaki∗ Department of Geriatric and Respiratory Medicine Tohoku University School of Medicine 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan ∗ Corresponding author. Tel.: +81-22-717-7182 fax: +81-22-717-7186 E-mail address: [email protected] (H. Sasaki) 10 September 2003
LETTER TO THE EDITOR
Effect of gefitinib (ZD1839) on metastatic brain tumour Fujiwara et al. described the case of a patient with advanced adenocarcinoma of the lung, in whom treatment, once-daily with 250 mg gefitinib demonstrated a marked anti-tumour effect, published in the April 2003 issue of Lung Cancer (pages 73–76) [1]. Gefitinib, a selective oral epidermal growth factor receptor- tyrosine kinase inhibitor, is expected as an important new therapy for chemotherapy-resistant non-small-cell lung cancer (NSCLC) [2–5]. However, little is known about the long-term effect of gefitinib on the metastatic lesions in the brain [1,6]. We present a patient with chemotherapy-resistant NSCLC who had multiple brain metastases prior to therapy with gefitinib, which produced a drastic but transient clinical response. A 56-year-old woman with advanced adenocarcinoma of the lung was admitted to hospital with
severe headache and dyspnoea in July 2002. She had previously received two different chemotherapy regimens (cisplatin, mitomycin and vinorelbine for 1 month, and gemcitabine and docetaxel for 4 months). She had had a partial response, but the disease progressed for 2 months after the final chemotherapy. On admission, she suffered from breathlessness and analysis of the bloodgas revealed hypoxaemia and hypocarbia, during breathing in air (PaO2 , 56 mm Hg and PaCO2 , 32 mm Hg, at pH 7.48). A contrasting computed tomography (CT) scan showed multiple brain metastases (arrows in Fig. 1A) and chest X-rays revealed diffuse pulmonary involvement. She started to receive an oral administration of gefitinib at 250 mg once daily. After 3 weeks of treatment, she noted a reduction in headaches and dyspnoea, and a follow-up examination showed complete resolution of the cerebral metastatic lesions by contrasted CT scan (Fig. 1B) as well as the diffuse pulmonary involvement on chest X-rays. A repeated analysis of bloodgas
Fig. 1 Contrasted CT scan of the brain shows multiple nodular lesions before gefitinib treatment (arrows in A). Multiple nodular lesions have completely resolved after 3 weeks of treatment with gefitinib (B). 0169-5002/$ – see front matter © 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.lungcan.2003.09.017
372 revealed normal values and she was discharged with the same dose of gefitinib in September 2002. However, the brain tumours recurred despite the maintenance therapy with gefitinib in April 2003. Finally, she died of brain metastases in June 2003, whereas the pulmonary primary lesions remained stable. The present case suggests that gefitinib may have a marked anti-tumour activity in the brain in some advanced NSCLC patients with brain metastases but the effect may be transient. Metastatic lesions from NSCLC may gain refractoriness to this agent more rapidly than primary lesions, but more clinical documentation is needed.
References [1] Fujiwara K, Kiura K, Ueoka H, et al. Dramatic effect of ZD1839 (‘Iressa’) in a patient with advanced non-small-cell lung cancer and poor performance status. Lung Cancer 2003;40:73—6. [2] Pallis AG, Mavroudis D, Androulakis N, et al. ZD1839, a novel, oral epidermal growth factor receptor-tyrosine kinase inhibitor, as salvage treatment in patients with advanced non-small cell lung cancer. Experience from a single center participating in a compassionate use program. Lung Cancer 2003;40:301—7.
Letter to the Editor [3] Lichtner RB, Menrad A, Sommer A, et al. Signaling-inactive epidermal growth factor receptor/ligand complexes in intact carcinoma cells by quinazoline tyrosine kinase inhibitors. Cancer Res 2001;61:5790—5. [4] Ranson M, Hammond LA, Ferry D, et al. ZD 1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors: results of a phase I trial. J Clin Oncol 2002;20:2240—50. [5] Sridhar SS, Seymour L, Shepherd FA. Inhibitors of epidermalgrowth -factor receptors: a review of clinical research with a focus on non-small-cell lung cancer. Lancet Oncol 2003;4:397—406. [6] Villano JL, Mauer AM, Vokes EE. A case study documenting the anticancer activity of ZD1839 (Iressa) in the brain. Ann Oncol 2003;14:656—8.
Hidenori Takahashi Takashi Ohrui Satoru Ebihara Mitsuhiro Yamada Hidetada Sasaki∗ Department of Geriatric and Respiratory Medicine Tohoku University School of Medicine 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan ∗ Corresponding author. Tel.: +81-22-717-7182 fax: +81-22-717-7186 E-mail address: [email protected] (H. Sasaki) 10 September 2003