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Readministration of gefitinib in a responder after treatment discontinuation due to gefinitib-related interstitial lung disease: a case report.

Takamochi K, Suzuki K, Bashar AH, Yajima K, Mochizuki T, Itaya T, Funai K - J Med Case Rep (2007)

Bottom Line: Gefitinib is considered to be well tolerated and less toxic compared with conventional cytotoxic drugs.However, interstitial lung disease (ILD) has been reported as a serious adverse effect.A reduced dose of gefitinib might be sufficient for patients having tumors with EGFR gene mutations, and that the currently approved dose may be excessively potent in some of these patients, thus resulting in the onset of adverse events.

View Article: PubMed Central - HTML - PubMed

Affiliation: First Department of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 435-3192 Japan. ktakamoc@hama-med.ac.jp.

ABSTRACT

Introduction: Gefitinib is a new molecular-targeted agent for the treatment of patients with advanced non-small cell lung cancer that fail to respond to conventional chemotherapy. Gefitinib is considered to be well tolerated and less toxic compared with conventional cytotoxic drugs. However, interstitial lung disease (ILD) has been reported as a serious adverse effect. The precise management of a gefitinib responder having severe adverse events remains unknown.

Case presentation: We report the case of gefitinib readministration in a patient with lung adenocarcinoma who had once responded but in whom treatment had to be discontinued owing to gefinitib-related ILD. A dramatic response was achieved both at the time of initial treatment (250 mg/day) and at readministration of gefitinib (125 mg/day). The effectiveness of gefitinib therapy in our patient could be explained in part by the presence of an activating mutation of epidermal growth factor receptor (EGFR) gene, L858R in exon 21, which was identified in the primary tumor.

Conclusion: A reduced dose of gefitinib might be sufficient for patients having tumors with EGFR gene mutations, and that the currently approved dose may be excessively potent in some of these patients, thus resulting in the onset of adverse events.

No MeSH data available.


Related in: MedlinePlus

Radiological evaluation of gefitinib-related interstitial lung disease on CT scans. (a) before treatment, (b) after treatment.
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Figure 2: Radiological evaluation of gefitinib-related interstitial lung disease on CT scans. (a) before treatment, (b) after treatment.

Mentions: However, the patient developed progressive general fatigue and shortness of breath 45 days after the initiation of gefitinib therapy. A chest CT scan demonstrated new areas of patchy ground glass opacity (GGO) accompanied by interstitial markings bilaterally, without evidence of tumor growth (Figure 2a). The serum LDH level was elevated to 457 IU/L (cut-off: 208 IU/L). To rule out infectious etiologies, we performed sputum cultures and relevant stainings for bacteria, fungi, and pneumocystis carinii, and the cytomegalovirous antigen test. None of these examinations were positive. Because of severe respiratory dysfunction, we could not perform bronchoscopy with bronchoalveolar lavage. Cardiogenic etiology was also excluded by electrocardiogram and echo cardiogram. Based on these findings, he was diagnosed as having gefitinib-related ILD, and gefitinib therapy was stopped. He was treated with high-dose corticosteroid (1 g/day of intravenous methylpredonisolone for three days) followed by a maintainace dose of 50 mg/day of oral prednisolone. The dose of oral prednisolone was decreased by 10 mg per week. After one month of steroid therapy, the patient reported marked improvement of dyspnoea. A chest CT scan showed resolution of GGO areas and interstitial markings, however the pulmonary metastatic lesions had slightly grown (Figure 2b). The serum LDH level was normalized two months after the initiation of steroid therapy.


Readministration of gefitinib in a responder after treatment discontinuation due to gefinitib-related interstitial lung disease: a case report.

Takamochi K, Suzuki K, Bashar AH, Yajima K, Mochizuki T, Itaya T, Funai K - J Med Case Rep (2007)

Radiological evaluation of gefitinib-related interstitial lung disease on CT scans. (a) before treatment, (b) after treatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2194710&req=5

Figure 2: Radiological evaluation of gefitinib-related interstitial lung disease on CT scans. (a) before treatment, (b) after treatment.
Mentions: However, the patient developed progressive general fatigue and shortness of breath 45 days after the initiation of gefitinib therapy. A chest CT scan demonstrated new areas of patchy ground glass opacity (GGO) accompanied by interstitial markings bilaterally, without evidence of tumor growth (Figure 2a). The serum LDH level was elevated to 457 IU/L (cut-off: 208 IU/L). To rule out infectious etiologies, we performed sputum cultures and relevant stainings for bacteria, fungi, and pneumocystis carinii, and the cytomegalovirous antigen test. None of these examinations were positive. Because of severe respiratory dysfunction, we could not perform bronchoscopy with bronchoalveolar lavage. Cardiogenic etiology was also excluded by electrocardiogram and echo cardiogram. Based on these findings, he was diagnosed as having gefitinib-related ILD, and gefitinib therapy was stopped. He was treated with high-dose corticosteroid (1 g/day of intravenous methylpredonisolone for three days) followed by a maintainace dose of 50 mg/day of oral prednisolone. The dose of oral prednisolone was decreased by 10 mg per week. After one month of steroid therapy, the patient reported marked improvement of dyspnoea. A chest CT scan showed resolution of GGO areas and interstitial markings, however the pulmonary metastatic lesions had slightly grown (Figure 2b). The serum LDH level was normalized two months after the initiation of steroid therapy.

Bottom Line: Gefitinib is considered to be well tolerated and less toxic compared with conventional cytotoxic drugs.However, interstitial lung disease (ILD) has been reported as a serious adverse effect.A reduced dose of gefitinib might be sufficient for patients having tumors with EGFR gene mutations, and that the currently approved dose may be excessively potent in some of these patients, thus resulting in the onset of adverse events.

View Article: PubMed Central - HTML - PubMed

Affiliation: First Department of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 435-3192 Japan. ktakamoc@hama-med.ac.jp.

ABSTRACT

Introduction: Gefitinib is a new molecular-targeted agent for the treatment of patients with advanced non-small cell lung cancer that fail to respond to conventional chemotherapy. Gefitinib is considered to be well tolerated and less toxic compared with conventional cytotoxic drugs. However, interstitial lung disease (ILD) has been reported as a serious adverse effect. The precise management of a gefitinib responder having severe adverse events remains unknown.

Case presentation: We report the case of gefitinib readministration in a patient with lung adenocarcinoma who had once responded but in whom treatment had to be discontinued owing to gefinitib-related ILD. A dramatic response was achieved both at the time of initial treatment (250 mg/day) and at readministration of gefitinib (125 mg/day). The effectiveness of gefitinib therapy in our patient could be explained in part by the presence of an activating mutation of epidermal growth factor receptor (EGFR) gene, L858R in exon 21, which was identified in the primary tumor.

Conclusion: A reduced dose of gefitinib might be sufficient for patients having tumors with EGFR gene mutations, and that the currently approved dose may be excessively potent in some of these patients, thus resulting in the onset of adverse events.

No MeSH data available.


Related in: MedlinePlus