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Table of Contents
Year : 2020  |  Volume : 3  |  Issue : 1  |  Page : 110-112

Metronomic chemotherapy and propranolol in a patient with metastatic angiosarcoma: Magic bullets?

1 Department of Medical Oncology, Aster Malabar Institute of Medical Sciences, Kozhikode, Kerala, India
2 Department of Nuclear Medicine, Aster Malabar Institute of Medical Sciences, Kozhikode, Kerala, India

Date of Submission26-Dec-2019
Date of Decision10-Jan-2020
Date of Acceptance27-Jan-2020
Date of Web Publication24-Feb-2020

Correspondence Address:
Arun Chandrasekharan
Department of Medical Oncology, Aster Malabar Institute of Medical Sciences, Mini Bypass Rd., Govindapuram, Kozhikode - 673 016, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/CRST.CRST_121_19

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How to cite this article:
Chandrasekharan A, Karunanithi S, Gangadharan K V. Metronomic chemotherapy and propranolol in a patient with metastatic angiosarcoma: Magic bullets?. Cancer Res Stat Treat 2020;3:110-2

How to cite this URL:
Chandrasekharan A, Karunanithi S, Gangadharan K V. Metronomic chemotherapy and propranolol in a patient with metastatic angiosarcoma: Magic bullets?. Cancer Res Stat Treat [serial online] 2020 [cited 2021 Oct 21];3:110-2. Available from: https://www.crstonline.com/text.asp?2020/3/1/110/279080

Angiosarcoma of the breast is an aggressive malignancy that can be primary in origin or can arise from a background of lymphedema or radiation. These malignancies frequently metastasize in spite of treatment and are challenging to treat.[1] We present a case of angiosarcoma of the breast that had early metastasis and progression on chemotherapy. Metronomic chemotherapy was subsequently used that led to clinical as well as radiological improvement lasting over 8 months.

Our patient was a 55-year-old female, who initially presented to us after a right modified radical mastectomy and axillary node dissection done at an outside center for a breast lump that was suggestive of a spindle cell neoplasm on biopsy. The final histopathology report was suggestive of a high-grade angiosarcoma with skin invasion; six nodes were dissected, which were reactive (T4bN0). Immunohistochemistry was not done. After a multidisciplinary tumor board discussion, it was decided to treat the tumor as a sarcoma, and she was started on intensity-modulated radiotherapy, 6000 cGy in thirty fractions to the chest wall and axilla. The axilla was given radiation in view of inadequate nodal dissection. She then received 12 cycles of weekly paclitaxel (80 mg/m2) and three cycles of 4-weekly liposomal doxorubicin (40 mg/m2). Liposomal doxorubicin was given, as the patient was frail with a performance status of two and would not have tolerated conventional doxorubicin. Four months later, she was diagnosed with collapse and compression of D3, D5, and L3 vertebrae with an adjacent soft-tissue mass. She received palliative radiotherapy to the dorsal spine and was started on weekly nanosomal albumin-bound paclitaxel along with monthly zoledronic acid. Anthracyclines and ifosfamide were not considered in view of the toxicity profile, recent exposure to doxorubicin, and patient frailty. As the patient had already received conventional paclitaxel 7 months ago, nanosomal albumin-bound paclitaxel was chosen to minimize the risk of peripheral neuropathy. After completing 12 weeks of chemotherapy in October 2018, she developed a rapidly progressing swelling along the mastectomy scar with significant bleeding from the lesion. She underwent emergency excision of the lesion, and hemostasis was achieved. Histopathology revealed a recurrent angiosarcoma with uninvolved margins and a positron-emission tomography-computed tomography (PET-CT) scan revealed new lesions in the brain, lung, liver, and skeleton. As the brain lesion was very small and the patient was asymptomatic, radiation to the brain was deferred.

She was started on a metronomic chemotherapy protocol consisting of vinblastine (6 mg/m2 intravenous bolus dose weekly), methotrexate (35 mg/m2 intravenous bolus dose weekly), and propranolol (orally 40 mg twice a day) given weekly from November 2018. Therapy was started without demonstrating the presence of β-adrenergic receptor on the histopathology specimen (this had not been tested). After 10 weeks of therapy, to assess response, PET-CT scan was done, which showed a partial response in the liver and lung with a resolution of uptake and sclerotic changes in the bone lesions. After 20 weeks, the PET-CT scan showed further regression of lesions [Figure 1] and [Figure 2]. After 31 weeks, PET-CT showed progressive lesions in the liver and bone, with a new lesion in the brain. She was started on whole-brain radiation, but developed an intratumoral bleed after one fraction and clinically deteriorated. In view of poor performance status, she was then planned for best supportive care alone.
Figure 1: Positron-emission tomography-computed tomography scan showing response to metronomic chemotherapy and propranolol. (a) Images taken before metronomic chemotherapy and propranolol. (b) Images taken after 5 months of metronomic chemotherapy and propranolol

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Figure 2: Positron-emission tomography-computed tomography scan showing partial response in the liver. (a) Images taken before metronomic chemotherapy and propranolol. (b) Images taken after 5 months of metronomic chemotherapy and propranolol

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Relapsed metastatic breast angiosarcoma has a poor outcome and is difficult to manage.[1] The disease spreads hematogenously primarily to the liver, lung, bone, soft-tissue, and lymph nodes. Cytotoxic chemotherapy (anthracyclines, ifosfamide, and taxanes) has been primarily used with single drug response rates of 16%–36%. Doublets have led to increased toxicity without much impact on outcomes.[2]

Recently, there has been accumulating evidence suggesting the role of blocking the β-adrenergic receptor in patients with angiosarcoma. This was tested in seven patients by Pasquier et al., with all patients showing response and one patient showing a complete response.[3] Banavali et al. also demonstrated a complete response lasting 20 months in patients treated with an oral combination of metronomic chemotherapy and propranolol.[4] Our patient progressed rapidly on conventional chemotherapy with multiple visceral metastases. She survived for 12 months once diagnosed with metastatic disease, of which she was on metronomic chemotherapy and propranolol for 8 months, showing a dramatic response, although short-lived. Although cerebrospinal fluid penetration of these drugs is poor, they exert their action on the brain through antiangiogenesis and activation of the dendritic cells.[5] The combination of vinblastine, methotrexate, and propranolol is easy to administer without too many side effects. The treatment is also cost effective and is easily affordable, especially among patients living in low-and middle-income countries.[6],[7] The cost of therapy for 8 months was around $250.

Angiosarcoma of the breast is a rare and aggressive tumor with few validated treatment options. The use of metronomic chemotherapy and propranolol can lead to very good responses and can be widely applied among all social groups.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Young RJ, Brown NJ, Reed MW, Hughes D, Woll PJ. Angiosarcoma. Lancet Oncol 2010;11:983-91.  Back to cited text no. 1
Mocellin S, Rossi CR, Brandes A, Nitti D. Adult soft tissue sarcomas: Conventional therapies and molecularly targeted approaches. Cancer Treat Rev 2006;32:9-27.  Back to cited text no. 2
Pasquier E, André N, Street J, Chougule A, Rekhi B, Ghosh J, et al. Effective management of advanced angiosarcoma by the synergistic combination of propranolol and vinblastine-based metronomic chemotherapy: A bench to bedside study. EBioMedicine 2016;6:87-95.  Back to cited text no. 3
Banavali S, Pasquier E, Andre N. Targeted therapy with propranolol and metronomic chemotherapy combination: Sustained complete response of a relapsing metastatic angiosarcoma. Ecancermedicalscience 2015;9:499.  Back to cited text no. 4
Demlova R, Melicharkova K, Rehak Z, Kren L, Oslejskova H, Sterba J. Successful use of metronomic vinblastine and fluorothymidine PET imaging for the management of intramedullary spinal cord anaplastic oligoastrocytoma in a child. Curr Oncol 2014;21:e790-3.  Back to cited text no. 5
Philip CC, Mathew A, John MJ. Cancer care: Challenges in the developing world. Cancer Res Stat Treat 2018;1:58-62.  Back to cited text no. 6
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Chandrasekharan A. Cancer care in the developing world: Is it all that morose? Cancer Res Stat Treat 2018;1:177.  Back to cited text no. 7
  [Full text]  


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