Erlotinib-induced Interstitial Lung Disease Research Articles

Atypical diffuse bilateral cystic lung changes secondary to erlotinib treatment in a patient with metastatic non-small cell lung carcinoma: A case report and literature review.

Erlotinib is a first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved in the first-line treatment of advanced non-small-cell lung cancer (NSCLC) patients with sensitizing epidermal growth factor receptor (EGFR) mutations. The response rate to erlotinib is ~60% and the incidence of erlotinib-induced interstitial lung disease (ILD) is ~1-4%. The Response Evaluation Criteria in Solid Tumours (RECIST) tool is commonly used to assess response to erlotinib; however, evaluation of response and subsequent progression in the presence of atypical cystic lung changes may be challenging. We herein present a rare case of diffuse cystic lung changes secondary to erlotinib treatment in a patient with EGFR mutation-positive metastatic NSCLC. Challenges in assessing atypical tumour response to erlotinib, pitfalls in using RECIST and differential diagnosis of TKI-related ILD are discussed in detail.

Outcome in advanced non-small cell lung cancer patients with successful rechallenge after recovery from epidermal growth factor receptor tyrosine kinase inhibitor-induced interstitial lung disease.

Several non-small cell lung cancer (NSCLC) cases of successful rechallenge with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) after recovery from gefitinib or erlotinib-induced interstitial lung disease (ILD) have been reported, but it is not clear whether the rechallenge affects the outcome. We retrospectively evaluated the difference in the outcome between advanced NCLC patients with active EGFR mutations who received EGFR-TKI rechallenge after recovery from EGFR-TKI-induced ILD and those who did not. EGFR-TKI-induced ILD occurred in 11 (10%) of 110 patients receiving gefitinib, five (7%) of 73 patients receiving erlotinib and one (8%) of 13 patients receiving afatinib. Diffuse alveolar damage pattern ILD was observed in six cases, four of which had chemotherapy-related death. Five of 13 patients who had recovered from ILD received EGFR-TKI rechallenge with concurrent oral administration of prednisolone 0.5mg/kg after the strict informed consent of the risk for the recurrence of severe ILD. All of the five patients achieved a partial response. The median overall survival from the occurrence of EGFR-TKI-induced ILD was longer in patients with EGFR-TKI rechallenge than that in patients without (15.5 vs. 3.5months, p = 0.029). The adverse events of EGFR-TKI rechallenge were tolerable, but one case receiving EGFR-TKI rechallenge with the suspected drug exhibited the recurrence of grade 3 ILD after the discontinuation of prednisolone. EGFR-TKI rechallenge with concurrent prednisolone therapy might be salvage therapy in advanced NSCLC patients with active EGFR mutations after recovery from EGFR-TKI-induced ILD.

Successful treatment of non-small-cell lung cancer with afatinib and a glucocorticoid following gefitinib- and erlotinib-induced interstitial lung disease: A case report.

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-induced interstitial lung disease (ILD) may be a life-threatening condition that may develop during treatment of lung cancer patients harboring EGFR mutations. We herein present the case of a 41-year-old female patient diagnosed with lung adenocarcinoma with an EGFR mutation (exon 19 deletion). The patient was treated with gefitinib followed by erlotinib and developed ILD induced by both EGFR-TKIs; furthermore, the patient acquired resistance to EGFR-TKI treatment. A repeat biopsy revealed a T790M mutation, which is associated with resistance to first-generation EGFR-TKIs, along with an exon 19 deletion identified by cytology of the pleural fluid. Treatment with afatinib and prednisolone resulted in tumor shrinkage, without worsening of the ILD. The present case demonstrated that combination treatment with afatinib and a glucocorticoid may be effective for the treatment of lung cancer patients who develop EGFR-TKI-induced ILD.

The combination of HLA-B*15:01 and DRB1*15:01 is associated with gemcitabine plus erlotinib-induced interstitial lung disease in patients with advanced pancreatic cancer.

PurposeIn a phase III study of gemcitabine plus erlotinib for advanced pancreatic cancer conducted in Canada, the incidence of interstitial lung disease (ILD) was 3.5 %. However, the incidence of ILD was reported as high as 8.5 % in a Japanese phase II study. These results suggest the influence of ethnic factors in the association of the use of gemcitabine plus erlotinib with the incidence of ILD. Here, we conducted a prospective study to analyze the relationship between human leukocyte antigen (HLA) alleles and ILD in Japanese patients with advanced pancreatic cancer receiving gemcitabine plus erlotinib.MethodsPatients were treated with gemcitabine (1000 mg/m2; administered by intravenous infusion on days 1, 8, and 15 every 4 weeks) and erlotinib (given orally at 100 mg/day). We compared the frequencies of HLA alleles in patients who did and did not develop ILD.ResultsA total of 57 patients were treated, and 4 patients (7.0 %) developed ILD. The combination of HLA-B*15:01 and DRB1*15:01 was observed in 2 of 4 patients (50 %) with ILD and in only 1 of 53 patients without ILD (2 %) resulting in odds ratio of 52.0 (95 % CI 3.2–842.5; p = 0.011).ConclusionThese results suggest that the combination of HLA-B*15:01 and DRB1*15:01 is associated with ILD in Japanese patients with advanced pancreatic cancer receiving gemcitabine plus erlotinib.Electronic supplementary materialThe online version of this article (doi:10.1007/s00280-016-3026-6) contains supplementary material, which is available to authorized users.

High-dose corticosteroid therapy for erlotinib-induced interstitial lung disease in Japanese patient with advanced pancreatic cancer.

Erlotinib is a selective epidermal growth factor receptor tyrosine kinase inhibitor used as a target therapy against non-small lung cancer and advanced pancreatic cancer. A regimen of erlotinib plus gemcitabine has been proven to prolong overall survival in the patient with advanced pancreatic cancer. In addition to common adverse effects, such as diarrhea, mucositis and skin rash (acne form eruptions), acute interstitial lung disease (ILD) has been reported as an infrequent but potentially fatal complication. We here report a case of a Japanese patient with erlotinib-induced ILD in whom high-dose corticosteroid therapy was successful. A fifty-five-year-old male with cancer of the head of the pancreas with multiple liver metastases started treatment with gemcitabine plus erlotinib. On the 13th day of erlotinib treatment, he had high fever. Chest computed tomography (CT) scan showed a diffuse ground-glass like infiltration of both lungs. He was diagnosed with ILD, and high-dose corticosteroid therapy was started. Two weeks after the introduction of steroid therapy, the reticular shadow faded away on CT. He was successfully treated with corticosteroid for erlotinib-induced acute ILD although he died 6 months after the initiation of chemotherapy owing to disease progression. we showed a case of a successfully treated Japanese patient of erlotinib-induced ILD. Because erlotinib-induced ILD would frequently occur in Japanese patients, closer attention to ILD should be paid for Japanese patients than in Western populations. If erlotinib-induced ILD occurs, a high-dose corticosteroid therapy would be a useful option of treatment.

Recurrent Interstitial Lung Disease Induced By Various Therapies for Non-Small Cell Lung Cancer

Erlotinib is a human epidermal growth factor receptor type 1 tyrosine kinase inhibitor which is used for non-small cell lung cancer treatment. Interstitial lung disease has been reported as an adverse event of erlotinib. We report the case of a 39-year-old man with erlotinib-induced interstitial lung disease in a non-small cell lung cancer patient. Although interstitial lung disease had improved by steroid therapy, palliative radiotherapy recalled the pneumonitis beyond the radiation fields. After the pneumonitis was well controlled, the patient was started on irinotecan, but the interstitial lung disease recurred shortly thereafter. We may have to abandon further cytotoxic therapies to avoid the recurrence of interstitial lung disease in patients who develop erlotinib-induced interstitial lung disease once.

Both gefitinib and erlotinib induced drug-related interstitial lung disease in a patient with pulmonary adenocarcinoma

Treatment for non-small-cell lung cancer with gefitinib and erlotinib is efficacious. However, while many studies have reported on gefitinib-related interstitial lung disease (ILD), less published data are available regarding erlotinib-induced ILD. Here, we report a case of pulmonary adenocarcinoma who developed ILD due to gefitinib initially and erlotinib thereafter. The two episodes of ILD were treated successfully with the discontinuation of the tyrosine kinase inhibitors and high-dose intravenous corticosteroids.

Successful Erlotinib Rechallenge in a Non-small Cell Lung Cancer Patient With Erlotinib-Induced Interstitial Lung Disease (ILD)

Successful Erlotinib Rechallenge in a Non-small Cell Lung Cancer Patient With Erlotinib-Induced Interstitial Lung Disease (ILD)

Four cases of interstitial lung disease induced by erlotinib and a review of the literatures

厄洛替尼是一种口服表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor tyrosine kinase inhibitor, EGFR-TKI），广泛应用于晚期非小细胞肺癌的治疗。尽管目前认为这类药物安全性良好，但可诱发严重的间质性肺病（interstitial lung disease, ILD）。文献中对吉非替尼所致ILD的报道较多，而对厄洛替尼所致的ILD报道较少。现报道上海市肺科医院4例厄洛替尼所致ILD，并复习相关文献，以使临床医生提高警惕。监测正在服用厄洛替尼患者的肺部症状、体征，做到及时诊断、尽早治疗对于厄洛替尼所致ILD的预后尤为重要。

Successful erlotinib rechallenge for leptomeningeal metastases of lung adenocarcinoma after erlotinib-induced interstitial lung disease: A case report and review of the literature

The most serious adverse reaction associated with treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is drug-induced interstitial lung disease (ILD). Because EGFR-TKIs are key drugs for patients with non-small cell lung cancer who have somatic activating mutations of the epidermal growth factor receptor gene (EGFR mutations), several cases of retreatment with EGFR-TKIs after ILD induced by these drugs have been reported. Here, we present a 68-year-old man with lung adenocarcinoma and leptomeningeal metastases having an EGFR mutation who was retreated with erlotinib after erlotinib-induced ILD. He suffered no ILD recurrence and his leptomeningeal metastases dramatically improved. In addition to the present case, reports of nine patients who were retreated with EGFR-TKIs after ILD were found in the literature. Only one patient had recurrence of ILD (although seven were retreated at a reduced dose of EGFR-TKIs, including the patient with recurrence). In contrast, three patients had no recurrence of ILD even without dose-reduction. These reports suggest that dose-reduction plays a limited role in preventing recurrence. Many patients received corticosteroids during retreatment, but not the one with recurrence of ILD. This may suggest that corticosteroids can prevent recurrence due to their antiinflammatory properties.

Erlotinib-induced acute interstitial lung disease associated with extreme elevation of the plasma concentration in an elderly non-small-cell lung cancer patient

We herein describe a case of drug-induced interstitial lung disease (ILD) following treatment with erlotinib. The plasma trough concentration of erlotinib at the time of the ILD diagnosis was extremely elevated compared with the plasma maximum concentration on day 1. We hypothesized that this phenomenon was associated with the pharmacodynamic interaction with a concomitant drug. The present case indicates that erlotinib-induced ILD was associated with a high plasma concentration of erlotinib. Oncologists should be aware of the possibility of ILD induced by erlotinib, especially for patients with co-morbidities.

Successful Erlotinib Rechallenge After Erlotinib-Induced Interstitial Lung Disease

CASE REPORT A 56-year-old nonsmoking Korean woman was diagnosed with stage 4 lung adenocarcinoma. Computed tomography (CT) scan showed a dominant left lung mass (Figure 1) with pulmonary, mediastinal, liver, adrenal, bone, and brain metastases. Erlotinib 150 mg daily and whole brain irradiation were started, and an epithelial growth factor receptor (EGFR) exon 19 mutation was detected. Symptoms improved until week 5 when she developed a new fever, worsening skin rash, and nonproductive cough. Erlotinib was held, and topical cleocin and oral doxycycline 200 mg daily were begun. Over the next 4 days, cough and dyspnea worsened with fall of O2 saturation to 92%, prompting repeat CT scan. This revealed a tumor response; however, new extensive bilateral ground glass opacities consistent with erlotinib-induced in

Fatal interstitial lung disease after erlotinib administration in a patient with radiation fibrosis

Although gefitinib used for the treatment of non-small-cell lung cancer is a well-known cause of interstitial lung disease (ILD), few case reports on erlotinib-induced ILD have been issued. The common risk factor of both of these two drug-induced ILDs is idiopathic interstitial pneumonia, but ILD in a patient with radiation fibrosis has not been previously reported. Report of a case. We recently experienced a case of fatal erlotinib-induced ILD, diagnosed based on clinical and radiologic findings, which occurred in a patient with radiation fibrosis. A 50-year-old male patient was started on erlotinib as a third-line chemotherapy. Six days after taking erlotinib, a chest radiograph showed rapid progression of reticular infiltration in both lung fields. High-resolution computed tomography scan findings were consistent with ILD, which was sufficient to diagnose as erlotinib-induced ILD. The patient died of respiratory failure after 8 days of steroid infusion and erlotinib discontinuation. Our case shows a fatal side effect of erlotinib. This case had radiation fibrosis, so we suggest that radiation fibrosis may be another contributor of the occurrence of ILD in patients taking erlotinib.

Recurrent Erlotinib-Induced Interstitial Lung Disease on Non-Small Cell Lung Cancer

1, Ⓡ ) has been considered to be a new, promising oral chemotherapy agent for local advanced or metastatic non-small cell lung cancer (NSCLC). Erlotinib is regarded as relatively safe, but interstitial lung disease (ILD) related to erlotinib has been reported on an infrequent basis in Asia. We report an histologically confirmed case of recurrent erlotinib-induced ILD. Although, the patient was highly responsive to the first erlotinib treatment, the therapy was discontinued due to erlotinib-induced ILD. After intravenous high dose methylpredinisolone treatment, ILD was improved rapidly by radiologic studies, but the particular lung cancer re-emerged. We restarted the patient erlotinib on low-dose oral methylpredinisolone, resulting in a recurrence of erlotinib-induced ILD. Our case suggests that re-administration of erlotinib should be performed on a limited basis in patients that have developed ILD on previous use, even if a therapeutic effect can be estimated.

Pulmonary Toxicity Associated With Erlotinib

Interstitial lung disease (ILD) related to therapy with the drug gefitinib has been well reported. The adverse pulmonary effects of erlotinib are less well known. We report a case of fatal pulmonary toxicity in a patient with advanced non-small cell lung cancer who received erlotinib. He had been found to have pathologic findings of usual interstitial pneumonia (UIP) on the resected lung cancer specimen prior to receiving erlotinib. This case and other published evidence should alert physicians to the possibility of fatal erlotinib-induced ILD. Similar to reports in patients receiving gefitinib, those with pathologic findings of UIP on resected lung specimens or known pulmonary fibrosis may be at particular risk for erlotinib pulmonary toxicity.