Annals of Oncology Advance Access originally published online on September 18, 2008
Annals of Oncology 2008 19(11):1977-1978; doi:10.1093/annonc/mdn641
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letters to the editor |
Fatal hemoptysis in a patient with breast cancer treated with bevacizumab and paclitaxel
In the studies investigating bevacizumab in metastatic breast cancer (MBC), Miller et al. [1, 2] described a low incidence of minor mucosal bleeding. Here, we describe a case of fatal hemoptysis occurring after the first bevacizumab infusion for MBC.In 2005, a 33-year-old woman with a hormone receptor-negative (RH–), human epidermal growth factor receptor 2 (HER2)-positive T2N0M0 breast cancer was treated with neo-adjuvant farmorubicin (100 mg/m2) with cyclophosphamid (500 mg/m2) and fluorouracil (500 mg/m2) 100 (four cycles), followed by mammectomy and axillary dissection. Pathology results showed a residual tumor (3.6 cm) without lymph node involvement. Adjuvant chemotherapy with docetaxel 100 mg/m2 (four cycles) was given, followed by radiation therapy and adjuvant trastuzumab. Trastuzumab treatment ended in March 2007. One year later, chest pain led to the diagnosis of bone metastasis. Computed tomography (CT) scan showed cerebral, liver, lung and bone metastases. Four lung metastases were localized close to blood vessels. A skin lesion was removed, revealing a RH– metastasis with no HER2 overexpression. Cranial radiation therapy was delivered because of headache. Chemotherapy (weekly paclitaxel with bevacizumab) was given 1 month after radiation therapy completion. Biological findings before chemotherapy infusion were normal except for moderate cholestasis with transaminase levels at the upper limit of normal range. Hemoglobin level and coagulation tests were normal. The first infusion of paclitaxel and bevacizumab was delivered with no immediate adverse event. Grade 1 hemoptysis occurred twice at day 2. The patient consulted at a local hospital at day 3. Biological findings showed anemia (9 g/dl) with no thrombocytopenia, associated with decreased prothrombin time and increased partial thromboplastin time. Liver parameters and serum creatinine level were not modified. CT scan was delayed because of iodine allergy. The patient refused immediate bronchoscopy, considering bleeding was minimal. Chest X-rays showed unilateral alveolar syndrome and due to fever, she was treated with amoxicillin with clavulanic acid. Since a pulmonary embolism was suspected by the practitioner, an injection of tinzaparin was delivered. The patient was referred to our hospital at the end of day 3. Hemoptysis relapsed during the night, leading to immediate death from massive hemorrhage. Autopsy was not carried out and coagulation abnormalities could not be further investigated.
To our knowledge, this is the first report of fatal hemorrhage in a patient with MBC treated with bevacizumab. The tinzaparin injection participated to this fatal side-effect of bevacizumab. Nevertheless, it must be pointed out that hemorrhage occurred twice very early after infusion of bevacizumab and that coagulation abnormalities came before anticoagulation was delivered. This lethal adverse event of bevacizumab was previously reported in lung cancers but not in MBC [3]. It suggests that anticoagulation must be avoided in patients with MBC receiving bevacizumab or delivered very cautiously if it is absolutely necessary. In addition, it raises the question of contraindicating bevacizumab in patients with centrally located lung metastases, similarly to patients with lung cancer [4]. Furthermore, bevacizumab has been reported to induce thrombotic microangiopathy [5]. We could not investigate further the coagulation parameters in this patient and the role of initial coagulation modifications in the sudden fatal evolution of this patient could not have been elucidated.
Departement of Medicale Oncology, Centre Henri Becquerel, Rouen cedex 1, France
* (E-mail: eblot{at}rouen.fnclcc.fr)
References
1. Miller KD, Chap LI, Holmes FA, et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol (2005) 23:792–799.
2. Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med (2007) 357:2666–2676.
3. Giaccone G. The potential of antiangiogenic therapy in non-small cell lung cancer. Clin Cancer Res (2007) 13:1961–1970.
4. Johnson DH, Fehrenbacher L, Novotny WF, et al. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol (2004) 22:2184–2191.
5. Eremina V, Jefferson JA, Kowalewska J, et al. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med (2008) 358:1129–1136.
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