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 70-year-old female patient without other relevant medical history was started on pemetrexed and carboplatin for mesothelioma after vitamin B12 and folic acid supplementation. The patient developed a rash on the anterior chest wall 7 days after the first cycle which persisted despite treatment with loratadine. Four days after the second cycle (14 days after the onset of the rash), the patient was admitted with widespread maculopapular eruptions treated with betamethasone valerate 0.1% cream along with cetirizine 10 mg twice daily. The patient’s additional symptoms were fever, pancytopenia, including neutropenia, seizures and confusion, pulmonary embolism, and nausea. Over the next few days, the rash continued to coalesce and spread. Forty days after the initial onset, 80% of the total body’s surface area (TBSA) was affected with beginning denudation (). Histology showed widespread epidermal necrosis with multiple dyskeratotic keratinocytes. A TEN-like reaction was diagnosed. Treatment with prednisone 50 mg daily to be weaned off by 10 mg every 7 days was initiated along with supportive measures. The patient could be discharged to the community in a stable condition 50 days after the initial rash. Chemotherapy was discontinued and palliative care was initiated due to the sADRs including the diagnosis of a TEN-like reaction.