Tammaro Kelly A, Baldwin Patricia D, Lundberg Ante S
Boston VA Health Care System, MA 02130, USA.
J Oncol Pharm Pract. 2005 Sep;11(3):127-30. doi: 10.1191/1078155205jp158cr.
To report a case of who a patient developed clinical and radiographical evidence of interstitial lung disease (ILD) on erlotinib after having tolerated gefitinib therapy.
A 58-year-old man with stage IV non-small-cell lung cancer (NSCLC) failed first and second line chemotherapy. He then received gefitinib, a small molecule epidermal growth factor receptor (EGFR) inhibitor, a therapy which was well tolerated, but did cause a grade 1 rash. On gefitinib, the patient's disease remained stable for seven months. Subsequent disease progression was treated with the newer EGFR inhibitor, erlotinib. After 5 days of erlotinib therapy, the patient presented with a sore throat and dyspnea, followed by a grade 2 rash and significant hemoptysis. Erlotinib was discontinued for three days, during which time his symptoms abated. Erlotinib was restarted and the patient again developed sore throat, dyspnea and severe hemotpysis, with progression of the rash to grade 3. Erlotinib therapy was discontinued and the patient recevied prednisone and supplemental oxygen. A CT scan of the chest demonstrated new areas of patchy ground glass opacity bilaterally and increased interstitial markings consistent with ILD.
The case demonstrates that clinical ILD can occur following erlotinib therapy, even in patients who previously tolerated gefitinib. ILD has not been reported to occur more frequently with erlotinib than with gefitinib. However, the dose of erlotinib employed clinically is the maximum tolerated dose identified in phase 1 trials, and is associated with an increased incidence of grade 3-4 rash and diarrhea, as compared to gefitinib. Thus, the observation of clinical ILD following erlotinib, but not gefitinib, may be the consequence of increased potency of erlotinib 150 mg/day compared to gefitinib 250 mg/day.
Clinical ILD can occur following erlotinib even in patients who previously tolerated gefitinib. IT is important to carefully monitor pulmonary symptoms in all patients who are receiving erlotinib, as early diagnosis and timely intervention are critical in managing drug-induced ILD.
报告一例患者在耐受吉非替尼治疗后，使用厄洛替尼时出现间质性肺疾病（ILD）的临床及影像学证据的病例。
一名58岁的IV期非小细胞肺癌（NSCLC）男性患者一线和二线化疗均失败。随后他接受了吉非替尼治疗，吉非替尼是一种小分子表皮生长因子受体（EGFR）抑制剂，该治疗耐受性良好，但确实出现了1级皮疹。使用吉非替尼期间，患者疾病稳定了7个月。随后疾病进展，患者接受了更新的EGFR抑制剂厄洛替尼治疗。厄洛替尼治疗5天后，患者出现咽痛和呼吸困难，随后出现2级皮疹和大量咯血。厄洛替尼停药3天，在此期间他的症状减轻。重新开始使用厄洛替尼后，患者再次出现咽痛、呼吸困难和严重咯血，皮疹进展为3级。停用厄洛替尼治疗，患者接受泼尼松和补充氧气治疗。胸部CT扫描显示双侧出现新的斑片状磨玻璃影以及与ILD相符的间质纹理增多。
该病例表明，即使是先前耐受吉非替尼的患者，使用厄洛替尼治疗后也可能发生临床ILD。尚未有报道称厄洛替尼导致ILD的频率高于吉非替尼。然而，临床上使用的厄洛替尼剂量是1期试验确定的最大耐受剂量，与吉非替尼相比，其3 - 4级皮疹和腹泻的发生率更高。因此，观察到厄洛替尼而非吉非替尼后出现临床ILD，可能是由于与每天250mg吉非替尼相比，每天150mg厄洛替尼的药效更强。
即使是先前耐受吉非替尼的患者，使用厄洛替尼后也可能发生临床ILD。对所有接受厄洛替尼治疗的患者仔细监测肺部症状非常重要，因为早期诊断和及时干预对于处理药物性ILD至关重要。
