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Leptomeningeal and medullary response to second-line erlotinib in lung adenocarcinoma.

A 61-year-old Caucasian female never-smoker (Eastern Cooperative Oncology group performance status 1) presented with stage IV, thyroid transcription factor 1-positive adenocarcinoma in October 2005. A 5-cm primary lesion was present in the left inferior lobe, with no nodal enlargement. Two cranial metastases, in the right temporal and frontal lobes, were the only metastases detected. Partial responses of the cranial and pulmonary lesions were achieved after treatment initiated in December 2005, consisting of whole-brain radiotherapy (total of 30 Gy), followed by five cycles of 3-weekly vinorelbine (30 mg/m days 1 and 8) and cisplatin (80 mg/m). During cycle 5 of chemotherapy, in March 2006, the patient’s global status deteriorated and an asymptomatic hypercalcemia, secondary to parathyroid adenoma, was diagnosed. Cisplatin was replaced with carboplatin and 4 mg zoledronic acid infusion administered, resulting in normalization of blood calcium. The partial responses of the lung and brain lesions were confirmed, and no bone metastases were detected. Chemotherapy was stopped, but monthly zoledronic acid was continued. In May 2006, an osteochondroma in the 12th lumbar vertebra was diagnosed; this was confirmed pathologically, and treated by laminectomy. The following month the patient was hospitalized for confusion. Cerebrospinal fluid (CSF) analysis revealed malignant cells and raised protein levels (1.02 g/liter). Magnetic resonance imaging (MRI) demonstrated no cranial lesion growth but leptomeningeal contrast enhancements were observed (Figure 1A). A chest computed tomography scan showed an increase in the size of the pulmonary lesion, and a new peripheral lesion (Figure 2A). The patient’s confusion did not respond to high-dose steroids (daily methylprednisolone 120 mg intravenously). Erlotinib (150 mg/d) and high-dose steroids were then coadministered. After 72 hours of treatment, the patient’s confusion lessened. Furthermore, malignant cells were absent from a second CSF sample (protein levels had decreased to 0.68 g/liter) obtained after 9 days of erlotinib therapy. Intravenous methylprednisolone was replaced with oral prednisolone and the steroid dose reduced to 30 mg. Erlotinib toxicity was limited to grade 1 skin rash. After 9 weeks of erlotinib treatment, the patient did not present any sign of confusion, and significant regression of the leptomeningeal contrast enhancements (Figure 1B) and the pulmonary lesion (Figure 2B) were observed. After 24 weeks of treatment, MRI scans revealed further leptomeningeal contrast enhancements. The cranial and pulmonary lesions were stable. As the patient was not symptomatic, erlotinib was continued. After 29 weeks of treatment, the patient was hospitalized again for confusion. Disease progression was documented by increased leptomeningeal contrast enhancements, and return of malignant cells and high protein levels (0.77 g/liter) in the CSF; lung lesions were not evaluated at this time. Erlotinib was increased to 300 mg/d, with high-dose steroids (daily methylprednisolone 120 mg intravenously). After 33 weeks of treatment, and despite a transient initial improvement, confusion worsened and best supportive care was initiated.