Author(s): Luigi Leo [*] aff1 , Francesca Caputo aff1 , Antonella Di Sarno aff1 , Tiziana Garofano aff1 , Francesca Andreozzi aff1 , Maria Grazia Massaro aff1 , Vincenzo Montesarchio aff1
breast cancer; eribulin; safety
Eribulin mesylate is a synthetic analog of halichondrin B, a natural product isolated from Halichondria okadai , a marine sponge. Eribulin acts by inhibiting microtubule polymerization, therefore inducing an irreversible mitotic block at the G2-M phase and eventually causing cellular apoptosis [1 ].
In the open-label Phase III EMBRACE study, conducted in heavily pretreated breast cancer patients, eribulin determined an advantage in overall survival (OS) compared with treatment of physician's choice [2 ]. More in detail patients on eribulin had a median OS of 13.2 months, median progression-free survival of 3.7 months and a 23% of clinical benefit, including overall response rate and stabilization (stable disease [SD]) lasting for at least 24 weeks. Moreover, eribulin was associated with an acceptable toxicity profile with asthenia and neutropenia being the most common adverse events; eribulin was also associated with peripheral neuropathy, which was the most common adverse event that led to treatment discontinuation.
Thanks to the results of the EMBRACE trial eribulin was approved for the treatment of patients with locally advanced or metastatic breast cancer who have progressed after at least two chemotherapeutic regimens, including anthracyclines and taxanes in either the adjuvant or the metastatic setting.
Patients enrolled in clinical trials are, however, often different from those encountered in daily practice [3 ], and therefore case reports and observational experiences do have a role in providing evidence on the optimal use of oncological therapies.
We report here our experience with eribulin mesylate in a heavily pretreated breast cancer patient with multiple bone metastases.
In July 1999, a 45-year-old Caucasian female was treated with mastectomy and omolateral axillary dissection for poorly differentiated invasive ductal carcinoma in her left breast. Her previous medical history and family history was unknown. Pathological tumor node metastasis stage was T2 (25 mm diameter) N1 (three positive lymph nodes). Proliferation index was high (Ki-67 30%), with 60% of ER positivity and PgR expression. No overexpression of HER2 receptors was documented. In line with international guidelines, the patient was treated with adjuvant chemotherapy with four courses of doxorubicin 75 mg/m2 every 3 weeks, followed by four courses of cyclophosphamide 600 mg/m 2 , methotrexate 60 mg/m2 and fluorouracil 600 mg/m2 on days 1 and 8 every 28 days. Thereafter, she received tamoxifen, at a dosage of 20 mg/day, for 3 years, until February 2001.
In February 2001, skeletal scintigraphy showed intense radioactivity in the last thoracic vertebrae (T12) and the first lumbar vertebra (L1). A CT scan reported multiple osteolytic lesions on the spinal column, from D8 to L1. Due to the severe bone pain and the risk of fractures, the patient was treated with palliative radiotherapy (30 Gy) on the affected area.
Since bone metastases were considered as ER positive, treatment with letrozole 2.5 mg/day and LH-RH analogs was initiated. The patient also received zoledronic acid...