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CASE REPORT
Year : 2022  |  Volume : 18  |  Issue : 6  |  Page : 1809-1810

An unusual infection with long-term bevacizumab treatment for advanced nonsmall-cell lung cancer: Actinomycosis


Department of Medical Oncology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey

Date of Submission17-Nov-2021
Date of Acceptance24-Jan-2022
Date of Web Publication12-Aug-2022

Correspondence Address:
Cihan Erol
Department of Medical Oncology, Faculty of Medicine, Ankara Yildirim Beyazit University, Çankaya, 06800, Ankara
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.jcrt_2083_21

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 > Abstract 


Bevacizumab is an angiogenesis inhibitor with Food and Drug Administration approval for multiple tumor types (including colon, nonsquamous nonsmall-cell lung cancer, kidney and glioblastoma multiforme, cervix, and ovarian cancer). Here, we present a patient with actinomycosis who was on treatment with bevacizumab maintenance therapy following chemotherapy combined with bevacizumab. A 60-year-old male patient with lung adenocarcinoma was treated four cycles of carboplatin, paclitaxel with bevacizumab. And then, bevacizumab maintenance therapy was continued. After 38 months of bevacizumab maintenance, computed tomography showed a newly developed cavitary lesion in the upper lobe of the right lung. Bronchoscopy was performed and the pathology report of the biopsy was reported as actinomycosis. Bevacizumab treatment was discontinued and the patient was treated with amoxicillin-clavulanate. To our knowledge, our case is the first case of actinomycosis infection due to the possible bevacizumab treatment.

Keywords: Actinomycosis, bevacizumab, Lung cancer


How to cite this article:
Erol C, Nahit Sendur MA, Yalçin B. An unusual infection with long-term bevacizumab treatment for advanced nonsmall-cell lung cancer: Actinomycosis. J Can Res Ther 2022;18:1809-10

How to cite this URL:
Erol C, Nahit Sendur MA, Yalçin B. An unusual infection with long-term bevacizumab treatment for advanced nonsmall-cell lung cancer: Actinomycosis. J Can Res Ther [serial online] 2022 [cited 2022 Dec 3];18:1809-10. Available from: https://www.cancerjournal.net/text.asp?2022/18/6/0/353710




 > Introduction Top


Bevacizumab is an angiogenesis inhibitor with Food and Drug Administration approval for multiple tumor types (including colon, nonsquamous nonsmall-cell lung cancer (NSCLC), kidney and glioblastoma multiforme, cervix, and ovarian cancer). The combination of chemotherapy and bevacizumab has become the new choice for advanced nonsquamous NSCLC treatment.[1] Bevacizumab can be added to platinum-based chemotherapy in eligible patients. The addition of bevacizumab to chemotherapy in the treatment of selected patients with advanced nonsquamous NSCLC resulted in a significant overall survival and progression-free survival (PFS) benefit.[2],[3],[4] After 4–6 cycles of chemotherapy in combination with bevacizumab, bevacizumab monotherapy is continued until the progression of the disease or intolerability due to toxicity.

Actinomycosis is a rare chronic infectious disease caused by Actinomyces spp., anaerobic Gram-positive bacteria that normally colonize the human mouth and digestive and genital tracts.

Here, we present a patient with actinomycosis who was on treatment with 38 months of bevacizumab maintenance therapy following chemotherapy combined with bevacizumab.


 > Case Report Top


A 60-year-old male patient was admitted to the hospital in May 2016 due to cough. On X-ray, a mass was detected in the left middle zone. Computed tomography (CT) was performed and showed masses in both lungs (the bigger one in the left, 80 mm × 75 mm). Transthoracic biopsy from the mass of the left lung was reported as adenocarcinoma. The patient was given four cycles of carboplatin, paclitaxel with bevacizumab. Partial response was achieved and bevacizumab (15 mg/kg) maintenance therapy was continued every 21 days. The mass of the left lung regressed from 80 mm to 11 mm. Treatment was continued with single-agent bevacizumab and followed as stable disease until September 2019. Cough and sputum complaints developed in September 2019 and CT was performed. CT showed a newly developed cavitary lesion in the upper lobe of the right lung [Figure 1]. Mediastinal lymph nodes also increased by up to 80%. Bronchoscopy was performed and the pathology report of the biopsy was reported as actinomycosis. Bevacizumab treatment was discontinued and amoxicillin-clavulanate treatment was given. After long-term antibiotic therapy (approximately 3 months), the patient died due to massive hemoptysis during follow-up imaging on January 14, 2020.
Figure 1: Newly developed cavitation in the right lung is seen in thorax tomography images. May 2019 (a) and September 2019 (b)

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 > Discussion Top


Many trials have proved the efficacy of adding bevacizumab to platinum-based chemotherapy in the treatment of patients with nonsquamous NSCLC. Although it has lagged behind in the era of immunotherapy, adding bevacizumab to chemotherapy is still a treatment option in developing countries. Median treatment with bevacizumab is seven cycles, with a range of one to 43 cycles.[5] In our patient, PFS was 38 months, whereas median PFS with adding bevacizumab to chemotherapy was about 6 months in many clinical trials.[6] Little is known about the long-term adverse events of maintenance therapy with bevacizumab. A recent report of NSCLC patients during the maintenance with bevacizumab observed grade 3 or 4 hematological toxicities in <1%; no grade 3 or 4 nausea, vomiting, or diarrhea; and no grade 5 toxicities.[7] In our case, there is no grade 3 or 4 toxicity.

Actinomyces are found in human normal mucosal flora and cannot cross the normal mucosal barrier. In conditions that impair the mucous integrity, such as trauma, operation, or intrauterine device, it can cross the mucosal barrier and cause infection. Other predisposing factors include; diabetes mellitus, immunosuppression, malnutrition, local tissue damage caused by neoplastic disease or irradiation. Bevacizumab causes cavity and necrosis due to the anti-vascular endothelial growth factor (VEGF) effect in long-term use. There are case reports showing that bevacizumab causes ulcers and necrosis, particularly of the skin and gastrointestinal tract.[8],[9] It does this with its anti-VEGF feature.[10] This creates a predisposing condition for actinomyces by disrupting the mucosal integrity. Therefore, it became a suitable environment for actinomycosis. Actinomycosis was detected in our case after 38 months of therapy. In this case, there is no medication other than bevacizumab. Therefore, we thought that it might be associated with the long-term use of bevacizumab. To our knowledge, our case is the first case of actinomycosis infection due to the possible bevacizumab treatment.

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 initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Bareschino MA, Schettino C, Rossi A, Maione P, Sacco PC, Zeppa R, et al. Treatment of advanced non small cell lung cancer. J Thorac Dis 2011;3:122-33.  Back to cited text no. 1
    
2.
Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, et al. Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: Results from a randomised phase III trial (AVAiL). Ann Oncol 2010;21:1804-9.  Back to cited text no. 2
    
3.
Lima AB, Macedo LT, Sasse AD. Addition of bevacizumab to chemotherapy in advanced non-small cell lung cancer: A systematic review and meta-analysis. PLoS One 2011;6:e22681.  Back to cited text no. 3
    
4.
Soria JC, Mauguen A, Reck M, Sandler AB, Saijo N, Johnson DH, et al. Systematic review and meta-analysis of randomised, phase II/III trials adding bevacizumab to platinum-based chemotherapy as first-line treatment in patients with advanced non-small-cell lung cancer. Ann Oncol 2013;24:20-30.  Back to cited text no. 4
    
5.
Crinò L, Dansin E, Garrido P, Griesinger F, Laskin J, Pavlakis N, et al. Safety and efficacy of first-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer (SAiL, MO19390): A phase 4 study. Lancet Oncol 2010;11:733-40.  Back to cited text no. 5
    
6.
Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006;355:2542-50.  Back to cited text no. 6
    
7.
Lopez-Chavez A, Young T, Fages S, Leon L, Schiller JH, Dowlati A, et al. Bevacizumab maintenance in patients with advanced non-small-cell lung cancer, clinical patterns, and outcomes in the Eastern Cooperative Oncology Group 4599 Study: Results of an exploratory analysis. J Thorac Oncol 2012;7:1707-12.  Back to cited text no. 7
    
8.
Mori Y, Ishikawa A, Urano N, Higuchi I, Gofuku J, Hasuike Y. Skin ulcer caused by bevacizumab – A case report. Gan To Kagaku Ryoho 2019;46:2237-9.  Back to cited text no. 8
    
9.
Tol J, Cats A, Mol L, Koopman M, Bos MM, van der Hoeven JJ, et al. Gastrointestinal ulceration as a possible side effect of bevacizumab which may herald perforation. Invest New Drugs 2008;26:393-7.  Back to cited text no. 9
    
10.
Tomita K, Saito Y, Suzuki T, Imbaby S, Hattori K, Matsuda N, et al. Vascular endothelial growth factor contributes to lung vascular hyperpermeability in sepsis-associated acute lung injury. Naunyn Schmiedebergs Arch Pharmacol 2020;393:2365-74.  Back to cited text no. 10
    


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