ArticlePDF Available

Outcome of ivermectin and doxycycline in cancer patients with COVID-19: A positive experience in Bangladesh

Authors:
International Journal of Molecular & Immuno Oncology • Article in Press | 1
is is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others
to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
©2020 Published by Scientic Scholar on behalf of International Journal of Molecular & Immuno Oncology
Short Communication
Outcome of ivermectin and doxycycline in cancer
patients with COVID-19: A positive experience in
Bangladesh
Syed Md Akram Hussain1, Md Shuayb2, Mahmudur Rahman3
1Department of Oncology, Square Hospitals, West Panthapath, Dhaka, Bangladesh, 2Vancouver Prostate Centre, Vancouver General Hospital, e University of
British Columbia, Vancouver, Canada, 3Emerging Infections Program, IDD, International Centre for Diarrhoeal Disease Research, Mohakhali, Dhaka, Bangladesh.
*Corresponding author:
Syed Md Akram Hussain,
Department of Oncology,
Square Hospitals,
WestPanthapath, Dhaka,
Bangladesh.
syedmdakram@gmail.com
Received : 17 September 2020
Accepted : 20 October 2020
Published :
DOI:
10.25259/IJMIO_30_2020
Quick Response Code:
e world, today, is facing an immense challenge with the outbreak of severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2) infection known as coronavirus disease 2019
(COVID-19). Bangladesh is the 16th ranked pandemic part of the world with 244,020 cases
diagnosed and 3234 deaths to date.[1] At present, no FDA approved remedies are available to defeat
this deadly disease. Ivermectin, an antiparasitic drug, has been found to inhibit the replication
of the SARS-CoV-2 virus in vitro.[2] When combined with doxycycline, an antibacterial drug,
ivermectin showed encouraging activity in reducing viral load, possible molecular mechanisms
of which have been proposed very recently.[3,4] Globally, a number of clinical trials are going on
to explore the activity of these two widely used FDA approved drugs as a potential therapy for
SARS-CoV-2 infection.
Although no systematic data are available, several studies including the European Society for
Medical Oncology and the National Institute for Health and Care Excellence guidelines have
reported that cancer patients are more vulnerable to develop COVID-19 infection.[5] We sought
to investigate the eectiveness of ivermectin plus doxycycline in COVID-19-positive cancer
patients in a tertiary care cancer center of Dhaka city in Bangladesh.
is is a case series conducted at the Oncology and Radiotherapy Centre of Square Hospital,
Bangladesh. A total of eight patients were treated with ivermectin and doxycycline combination
to date, who met the eligibility criteria. e primary outcome was treatment response and the
secondary outcome was treatment-related toxicity. Inclusion criteria included in this study were
patients with any stage of solid malignancies or lymphoma proved by pathology; active disease
being treated with chemotherapy and/or radiotherapy, biological agent, hormone therapy, or
immunotherapy in neoadjuvant, adjuvant, concurrent or palliative setting; ECOG performance
status 0–2; age between 18 and 75 years; RT-PCR positive for SARS-CoV-2; have any of the
symptoms of temperature ≥37.5, cough, or sore throat; and provided informed written
consent. e exclusion criteria were allergy to ivermectin or doxycycline; received ivermectin,
doxycycline, hydroxychloroquine, or chloroquine phosphate within the past 4 weeks; a history
of chronic heart, liver, or kidney diseases; pregnant or lactating women; multiple primary
malignancies; and joined in other clinical trials.
When came to our outpatient department for their scheduled cancer treatment, RT-PCR for
COVID-19 was done as per the routine protocol of the hospital. No patient was found to be
www.ijmio.com
International Journal of Molecular &
Immuno Oncology
Article in Press
Hussain, et al.: Ivermectin in cancer patients with COVID-19
International Journal of Molecular & Immuno Oncology • Article in Press | 2
impaired immune systems, that is, no leukocytopenia,
thrombocytopenia, or not receiving immunosuppressants.
All presented with mild symptoms of COVID-19 [Table1].
Scheduled treatment (chemotherapy and/or radiotherapy)
was postponed, once COVID-19 was conrmed and started
tablet ivermectin (12 mg for patients with 80 kg weight
and 18 mg for those with above 80 kg weight) single dose
and Tablet doxycycline (100 mg) twice daily for 5 days.
Parallelly, the patients received supportive management
for their symptoms. On day 6, nasal swabs were collected
for RT-PCR for SARS-CoV-2 which appeared negative
for all patients, and the consecutive test was done on day 7
also appeared negative. All patients became free from the
symptoms of COVID-19 aer this period. en, their cancer
treatment was resumed with intensive surveillance. ere
was no reported toxicity of epigastric distress, abdominal
discomfort, vomiting, diarrhea, or skin rash.
e World Health Organization estimated that the period
of this viral shedding is up to 9 days and 20 days for
the patients with mild symptoms and for those who are
hospitalized, respectively.[1] We report data of eight SARS-
CoV-2-infected cancer patients who were treated with
ivermectin and doxycycline combination and recovered in 6
days only. In addition, our patients remained non-infectious
to other people in the hospital as the successive two PCR
tests were negative. Ongoing oncological managements
were not compromised for any of the patients, except the
5-day treatment delay over the duration of ivermectin plus
doxycycline therapy. All patients were able to complete
the remainder of their chemotherapy and/or radiotherapy
without any serious adverse events.
Managing cancer patients are challenging in the era of
COVID-19 of today. Despite the fact that the risk/benet
ratio of cancer treatment is important without imposing the
patients of being further immunosuppressed and seriously
ill from SARS-CoV-2 infection, cancer-related mortality
must not be ignored. Especially for curable cancers, the
continuation of active oncological management is crucial to
achieve cure and survival benets. Alteration of treatment
regimens, switching to oral treatment, long-term treatment
breaks all can seriously threaten the treatment outcome of
cancer patients even for those who are in palliative settings.
Ivermectin plus doxycycline therapy, though tested in a
very small number of patients in our study, resulted in very
promising activity against COVID-19, and this is the rst-
ever data yield from cancer patients. We believe that our
preliminary ndings could be used as a building block for
future large-scale studies, and randomized controlled trials
including only cancer patients are warranted to validate the
ecacy of this therapy.
Declaration of patient consent
e authors certify that they have obtained all appropriate
patient consent.
Financial support and sponsorship
Nil.
Conicts of interest
ere are no conicts of interest.
Table1: Characteristics of COVID-19-infected cancer patients treated with oral ivermectin plus doxycycline.
Patient Diagnosis Stage Age Comorbidity Ongoing cancer treatment COVID-19
symptoms
Case 1 Gestational
trophoblastic tumor
FIGOa Prognostic
score III
35 Nil 2 weekly intramuscular methotrexate Fever
Case 2 Breast cancer IIB 60 Nil Adjuvant chemotherapy with doxorubicin
and cyclophosphamide
Fever
Case 3 Head and neck
cancer
II 60 DMb, HTNcDenitive CCRTd with weekly cisplatin Fever and
cough
Case 4 Breast cancer IIB 40 Nil Adjuvant chemotherapy with doxorubicin
and cyclophosphamide
Fever and
mild cough
Case 5 Breast cancer IIIC 62 DMbAdjuvant chemotherapy with epirubicin
and cyclophosphamide
Fever
Case 6 Lung cancer IIIC 70 HTNcCCRTd with weekly paclitaxel and
carboplatin
Fever and
cough
Case 7 Biliary tract cancer IIIB 67 DMb, HTNcAdjuvant chemotherapy with 4 weekly
gemcitabine
Fever
Case 8 Breast cancer IIIC 53 Nil Adjuvant endocrine therapy with letrozole Fever, mild
cough
aFIGO: International Federation of Gynecology and Obstetrics, bDM: Diabetes mellitus, cHTN: Hypertension, dCCRT: Concurrent chemoradiation therapy
Hussain, et al.: Ivermectin in cancer patients with COVID-19
International Journal of Molecular & Immuno Oncology • Article in Press | 3
REFERENCES
1. WHO Coronavirus Disease (COVID-19) Dashboard. World
Health Organization. Available from: https://www.covid19.
who.int. [Last accessed on 2020 Aug 10].
2. Caly L, Druce JD, Catton MG, Jans DA, Wagsta KM. e
FDA-approved drug ivermectin inhibits the replication of
SARS-CoV-2 in vitro. Antiviral Res 2020;178:104787.
3. Maurya DK. A Combination of Ivermectin and Doxycycline
Possibly Blocks the Viral Entry and Modulate the Innate
Immune Response in COVID-19 Patients. New York:
ChemRxiv; 2020.
4. Hussman JP. Cellular and Molecular Pathways of COVID-19
and Potential Points of erapeutic Intervention. Front
Pharmacol 2020;11:1169.
5. Cortiula F, Pettke A, Bartoletti M, Puglisi F, Helleday T.
Managing COVID-19 in the oncology clinic and avoiding the
distraction eect. Ann Oncol 2020;31:553-5.
How to cite this article: Hussain SM, Shuayb M, Rahman M. Outcome of
ivermectin and doxycycline in cancer patients with COVID-19: A positive
experience in Bangladesh. Int J Mol Immuno Oncol, doi: 10.25259/
IJMIO_30_2020
... On December 11, a peer-reviewed early treatment case series study in Bangladesh by Hussain et al. with 8 patients resulted in all patients testing negative by day six [206]; [207]. ...
Preprint
Full-text available
First part part of the timeline covering a period from April 2020 to March 2021 (this is an extended version of an earlier preprint written on March 24, 2021. Changes: Abstract, Introduction, April 26, September 25, December 7, February 9, March 15, from March 22 to March 31, Discussion) *** Other parts: Part 0: https://www.researchgate.net/publication/348077948 *** *** Part 2: https://doi.org/10.13140/RG.2.2.16973.36326 *** Part 3: https://doi.org/10.13140/RG.2.2.23081.72805 *** Part 4: https://doi.org/10.13140/RG.2.2.26000.53767 *** Part 5: https://doi.org/10.13140/RG.2.2.35015.16807 *** Additional notes (Feb-Apr 2022): https://doi.org/10.13140/RG.2.2.24356.55682 ***
... On December 11, a peer-reviewed early treatment case series study in Bangladesh by Hussain et al. with 8 patients resulted in all patients testing negative by day six. 194,195 On December 11, an article by Associated Press, "a part of The Associated Press' ongoing effort to factcheck misinformation that is shared widely online, including work with Facebook to identify and reduce the circulation of false stories on the platform", discussed Kory's Senate Committee testimony mentioning it had received one million views on YouTube, and referring to comments by two infectious disease experts it concluded that "there's no evidence ivermectin has been proven a safe or effective treatment against COVID-19". 196 On December 12, a post on FLCCC Alliance Facebook page noted that YouTube had taken down the video of Kory's US Senate Committee testimony. ...
Preprint
Full-text available
This is an outdated version of the first part of the timeline. Please see current versions *** Part 0: https://www.researchgate.net/publication/348077948 *** Part 1: https://doi.org/10.13140/RG.2.2.13705.36966 *** Part 2: https://doi.org/10.13140/RG.2.2.16973.36326 *** Part 3: https://doi.org/10.13140/RG.2.2.23081.72805 *** Part 4: https://doi.org/10.13140/RG.2.2.26000.53767 *** Part 5: https://doi.org/10.13140/RG.2.2.35015.16807 *** Additional notes (Feb-Apr 2022): https://doi.org/10.13140/RG.2.2.24356.55682 ***
Article
Full-text available
With the objective of linking early findings relating to the novel SARS-CoV-2 coronavirus with potentially informative findings from prior research literature and to promote investigation toward therapeutic response, a coherent cellular and molecular pathway is proposed for COVID-19. The pathway is consistent with a broad range of observed clinical features and biological markers and captures key mediators of pathophysiology. In this proposed pathway, membrane fusion and cytoplasmic entry of SARS-CoV-2 virus via ACE2 and TMPRSS2-expressing respiratory epithelial cells, including pulmonary type-II pneumocytes, provoke an initial immune response featuring inflammatory cytokine production coupled with a weak interferon response, particularly in IFN-λ–dependent epithelial defense. Differentiation of non-classic pathogenic T-cells and pro-inflammatory intermediate monocytes contributes to a skewed inflammatory profile, mediated by membrane-bound immune receptor subtypes (e.g., FcγRIIA) and downstream signaling pathways (e.g., NF-κB p65 and p38 MAPK), followed by chemotactic infiltration of monocyte-derived macrophages and neutrophils into lung tissue. Endothelial barrier degradation and capillary leakage contribute to alveolar cell damage. Inflammatory cytokine release, delayed neutrophil apoptosis, and NETosis contribute to pulmonary thrombosis and cytokine storm. These mechanisms are concordant with observed clinical markers in COVID-19, including high expression of inflammatory cytokines on the TNF-α/IL-6 axis, elevated neutrophil-to-lymphocyte ratio (NLR), diffuse alveolar damage via cell apoptosis in respiratory epithelia and vascular endothelia, elevated lactate dehydrogenase (LDH) and CRP, high production of neutrophil extracellular traps (NETs), depressed platelet count, and thrombosis. Although certain elements are likely to be revised as new findings emerge, the proposed pathway suggests multiple points of investigation for potential therapeutic interventions. Initial candidate interventions include prophylaxis to augment epithelial defense (e.g., AT1 receptor blockade, type III and type I interferons, melatonin, calcitriol, camostat, and lopinavir) and to reduce viral load (e.g., remdesivir, ivermectin, emetine, Abelson kinase inhibitors, dopamine D2 antagonists, and selective estrogen receptor modulators). Additional interventions focus on tempering inflammatory signaling and injury (e.g., dexamethasone, doxycycline, Ang1-7, estradiol, alpha blockers, and DHA/EPA, pasireotide), as well as inhibitors targeted toward molecular mediators of the maladaptive COVID-19 immune response (e.g., IL-6, TNF-α, IL-17, JAK, and CDK9).
Article
Full-text available
Although several clinical trials are now underway to test possible therapies, the worldwide response to the COVID-19 outbreak has been largely limited to monitoring/containment. We report here that Ivermectin, an FDA-approved anti-parasitic previously shown to have broad-spectrum anti-viral activity in vitro, is an inhibitor of the causative virus (SARS-CoV-2), with a single addition to Vero-hSLAM cells 2 hours post infection with SARS-CoV-2 able to effect ∼5000-fold reduction in viral RNA at 48 h. Ivermectin therefore warrants further investigation for possible benefits in humans.
A Combination of Ivermectin and Doxycycline Possibly Blocks the Viral Entry and Modulate the Innate Immune Response in COVID-19 Patients
  • D K Maurya
Maurya DK. A Combination of Ivermectin and Doxycycline Possibly Blocks the Viral Entry and Modulate the Innate Immune Response in COVID-19 Patients. New York: ChemRxiv; 2020.