A 63-year-old male (an ex-smoker that quit 20 years ago, with smoking history of 15 pack-years) was referred to our outpatient clinic with NSCLC diagnosis to assess treatment options. The tumour was located in the right lung and spread to the mediastinal and supraclavicular lymph nodes. The lesion was detected in the chest CT (April, 2015) performed due to recurring mild exertional dyspnoea, decrease in exercise tolerance and dry paroxysmal cough. On histopathological examination of mediastinal lymph nodes biopsy obtained at mediastinoscopy and the right supraclavicular lymph nodes from fine-needle biopsy metastatic lung adenocarcinoma (TTF1+, Napsin A+) was diagnosed (June, 2015). The patient denied any weight loss. His medical history included mild prostatic hyperplasia, past lithotripsy due to urolithiasis, and in his youth hepatitis A. He is a farm worker.\nThe results of laboratory testing were within normal limits. The chest CT revealed suspicious additional changes in the lung parenchyma as well as bone lesions suggestive of metastases. In PET scan distant metastases were ruled out, however, due to significant regional spread of tumour (stage IIIB) the patient was not eligible for radical radiotherapy. In parallel to the staging procedures, the status of EGFR activating mutations was assessed and the exon 19 deletion was detected. The patient was therefore started on afatinib 40 mg QD.\nAfter 4 weeks of treatment the patient presentedwith a facial rash (grade 1). After 12 weeks of treatment diarrhoea ensued, however, the patient remained professionally active. Diet modification and loperamide as needed were advised. In the chest CT performed after 12 weeks of treatment there was a partial tumour response. With no laboratory abnormalities, the patient continued therapy for 12 months. The rash with no need of treatment persisted.\nIn August 2016 the patient experienced a pathological vertebral fracture with no evidence of lung cancer progression on chest imaging and no evidence of disease progression in the brain MRI. However, a few days later there appeared progressive paraparesis. The spine MRI revealed metastases in vertebral bodies of Th1, Th7 and Th8 with protrusion into the epidural space and spinal cord compression. The patient underwent neurosurgery (posterior decompression and C4-Th11 stabilisation), rehabilitation (physiotherapy and kinesitherapy) and palliative radiotherapy (30 Gy in 10 fractions) for affected area. The treatment with afatinib was continued.\nIn December 2016 (15th month of afatinib treatment) the chest CT revealed progression of the disease in the lungs. Genetic examination of circulating free DNA (cfDNA) was performed and EGFR T790M mutation was found. In December 2016 the treatment with osimertinib 80 mg QD was initiated. The severity of the neurological deficits was slowly improving and the patient recovered the ability to move his legs. Follow-up chest CT, performed after 2 months of treatment, revealed partial regression. In the following examination further regression was observed, with the sum of measurable dimensions of the lesions reduced in size by 38%. Currently, the patient is still experiencing a clinical benefit after 8 months of osimertinib treatment.
A 42-year-old woman diagnosed with stage IV NSCLC (adenocarcinoma) was admitted to our hospital in August 2013 and given an AP regimen (pemetrexed 500 mg/m2 on day 1, cisplatin 75 mg/m2 on days 1 to 3, repeated every 3 weeks) as initial chemotherapy on August 2nd, 2013. She received folate, vitamin B12, and corticosteroids as recommended. Several days later, her EGFR genetic test results demonstrated an exon 19 mutation (L747-T751>P); thus, she started taking gefitinib (250 mg once daily) on August 15th. On August 23th, which was 21 days after AP chemotherapy and 8 days after gefitinib treatment, the patient suddenly developed a widespread eruption including acne-like rash on the face, erythema papules on the trunk and limbs, oral ulcer, and conjunctivitis ( and ), followed by a fever of 39°C. The rash gradually increased and aggravated, accompanied with blisters, pruritus, and ulceration. Twelve days after gefitinib treatment, the patient was hospitalized. Gefitinib was immediately stopped, and imipenem, amikacin, and fluconazole were administered intravenously as prophylaxis, and diphenhydramine and loratadine were given as an anti-allergy treatment. On the 13th day, the patient's condition deteriorated further with a fever of 42°C, fused mucocutaneous rash as well as diffuse vesicles and bullae ( and ), which coalesced and then sloughed, presenting a scalded appearance. A positive Nikolsky sign was present on her back and feet ( and ). After consulting dermatology doctors, the patient was diagnosed with TEN and transferred to the Dermatology Department at the Second Affiliated Hospital of Sun Yat-sen University for further treatment.\nRoutine laboratory testing showed a white blood cell (WBC) count of 6.26 × 109/L [reference value: (3.69-9.16) × 109/L], neutrophil (NEU) proportion of 73.1% (reference: 50%-70%), and C-reactive protein (CRP) level of 16.36 mg/L (reference: 0-8.2 mg/L); both the Mycoplasma pneumoniae IgM antibody and Mac strains were negative. No suspicious fungus was found in the oral swab examination, nor did bacteria grow in the skin secretion culture.\nImmunosuppressive treatment was started with 100 mg methylprednisolone (daily injection) for 9 days and intravenous immunoglobulin (20 g/day) for 5 days, followed by 10 g/day for 5 days, accompanied with imipenem and teicoplanin for anti-infection and other supportive treatment. This treatment led to a recurrence of the rash and the mucosal lesions, reepithelization of the denuded skin (), and improvement of the patient's general condition within 40 days. A chest computed tomography (CT) scan and brain magnetic resonance imaging (MRI) showed partial remission after treatment. The combination of AP and gefitinib was suspended; accordingly, the patient began treatment with icotinib (another EGFR-TKI made in China) after recovery, without exfoliative dermatitis or other similar toxicities. Stable disease was later achieved.