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Intrathecal trastuzumab and thiotepa for leptomeningeal spread of breast cancer.

A 31-year-old woman underwent a right segmental mastectomy in October 1999 for a pT2, pN2 invasive ductal carcinoma, negative for estrogen receptor/progesterone receptor, positive for amplification of human epidermal growth factor receptor-2 (HER-2). She received adjuvant chemotherapy (doxorubicin + cyclophosphamide, followed by paclitaxel) and local radiotherapy. Two and a half years after surgery, she developed multiple liver metastases. She received i.v. carboplatin, paclitaxel, and trastuzumab, followed by capecitabine and trastuzumab, with a radiological complete response. Approximately 14 months later (April 2004), a single brain lesion was detected on magnetic resonance imaging (MRI), in the right occipital lobe. The lesion was surgically resected, followed by external beam whole-brain radiation. In August 2006, the patient presented with visual impairment, ptosis of the right eye, right hemi-facial hypoesthesia, left foot drop, and paralysis of the left facial nerve. An MRI exam revealed a right occipital brain lesion (1.5 cm), diffuse leptomeningealmetastases (LM), a cervical extramedullary intradural enhancing lesion (C1– C3), an intramedullary lesion centered at T12, and a nodular area of enhancement on the roots of the cauda equina. Only a suspicious 6-mm lung nodule was found on systemic restaging. A diagnostic lumbar puncture was carried out, and cytology of the cerebro-spinal fluid (CSF) was positive for cancer cells (5%of malignant cells). CSF glucose, lactate dehydrogenase, and protein levels were always normal. After placement of an Ommaya reservoir, she was started on intrathecal (i.t.) trastuzumab, initially on a weekly schedule, with gradual dose increase from 20 to 30 mg (Table 1), later combined with i.t. methotrexate (10 mg) for two doses. To reduce the risk of anaphylaxis and neurotoxicity from the preservative agent [1], i.t. trastuzumab was administered without the diluent provided. Interestingly, after the first dose of i.t. trastuzumab, all subsequent CSF cytologies were negative for malignant cells. After the two first doses of i.t. trastuzumab, we also started i.v. trastuzumab, that was never interrupted afterwards, and i.v. pegylated liposomal doxorubicin (PLD; letters to the editor Annals of Oncology