In light of promising results of hydroxychloroquine in COVID-19, should we consider using it prophylactically in cancer patients, especially if immunocompromised?   

Acknowledging that there is no time for good trials yet in this setting

Question Created by Elie Chalhoub


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Maria Suarez-Almazor, MD Anderson Cancer Center
Added March 24, 2020
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Radiation Oncologist, Chairman, Radiation Oncology, Academic Institution (South)
March 25, 2020

I agree that prophylactic use at large is difficult to justify or rationalize. However, the recently published French study on viro-positive patients shows that viral shedding decreases dramatically and by 1 week, a substantial majority stop shedding if given chloroquine. Based on these preliminary, non-randomized data in a small select patient cohort, I would be a proponent of a randomized RT trial (could be done by institutional randomization, as one example) of viro-positive patients who are put on a break while undergoing or starting RT, and checking for viral shedding with or without hydroxychloroquine (and actually in the French trial, the combo of chloroquine and azithromycin was the most effective for this specific endpoint).

Radiation Oncologist, Radiation Oncology, Community Practice (Northeast)
March 25, 2020

No, hydroxychloroquine is probably not an effective treatment or prophylactic agent. I agree that it is important to protect our cancer patients. In the Chinese experience with hospitalized COVID-19 patients, patients with a cancer history had almost a fivefold higher risk of dying or being placed on a ventilator. If there was an effective prophylactic agent we should use it. But hydroxychloroquine is not the answer.

There are limitations on any study that uses throat or NP swabs as the sole measure of disease activity  COVID-19 starts as a “head cold”, then becomes a “chest cold” according to a German study. Virus persists longer in the lungs than it does in the throat. In this study 5/9 untreated patients cleared their throat swabs after day 5, but most had persistent disease in the sputum. Viral clearance from the nasopharynx, but persistence in the lungs, is the natural history of the disease. This is why there have been patients with negative throat swabs, who were told they recovered, but later died of the disease.  It’s the disease in the lungs that kills people not the disease in the throat or nasopharynx. This is also the flaw in the below French study, which only looked at NP swabs.

A French Study found that six patients taking hydroxychloroquine and azithromycin were more likely to have negative nasopharyngeal swabs after day five than the control group. But a more recent study found that hydroxychloroquine was ineffective. In this Chinese study 13/ 15 patients given hydroxychloroquine and supportive care had cleared their throat swabs on day 7, and 14/15 given supportive care only, had cleared their throat swabs on day 7. By day 14 all patients had cleared their throat swabs. Thus hydroxychloroquine is no better than supportive care. Supportive care included lopinavir/ritonavir (which was found ineffective in a different Chinese study). One patient treated with hydroxychloroquine progressed to severe disease during the study.

Thus there really is no evidence to support the use of hydroxychloroquine as a treatment or prophylactic agent as of today, March 25, 2020. If patients want a preventative, I would have them wear surgical masks, use good hand hygiene, avoid crowds, take vitamin C and zinc supplements. Masks and hand hygiene definitely help, and vitamin C and zinc are of psychological benefit.

Radiation Oncologist, Community Practice (South)
March 25, 2020

Now I am really confused. What I am understanding from @Eli D. Finkelstein is that there is absolutely no benefit to HC, C, or combination with Z pack. So, am I to assume that some of the positive studies we see are somehow subjectively slanted, and all the ongoing/upcoming trials in the US should be abandoned?

, Professor, Academic Institution (South)
March 25, 2020

More data is needed. I'm hearing anecdotally that many patients are receiving antimalarials outside protocols which is unfortunate, as we need good data to give robust recommendations. I am assuming New York will be able to provide at least some preliminary data soon, even if uncontrolled.

Radiation Oncologist, Radiation Oncology, Community Practice (Northeast)
March 25, 2020

@Andrejs V. Strauss I didn't mean to give the impression that I was against randomized trials of HC. I totally agree with @Maria E. Suarez-Almazor, we need more data from proper clinical trials. I just wanted to summarize the data that exists today. There is a positive French Trial of HC with 6 patients in the experimental arm, and negative Chinese trial of HC with 15 patients in the experimental arm. Only the Chinese paper reported clinical outcomes which were slightly worse in the experimental arm. The issue has been raised, it needs to be put to rest with clinical trials. The data in support of HC is very, very weak as of today.

Radiation Oncologist, Community Practice (South)
March 25, 2020

Thank you for clarifying!!!

Radiation Oncologist, Radiation Oncology, Community Practice (Northeast)
March 26, 2020

@Andrejs V. Strauss I sincerely hope I'm wrong about the efficacy of the HC Azithromycin combo. It would be great if we have something that works now. The epidemic is peaking in Italy, the daily number of new cases is dropping. So there is hope on the horizon.

Radiation Oncologist, Community Practice (South)
March 26, 2020

I do as well, as I have an immune compromised (medically) family member, who works with immune compromised patients!!

Radiation Oncologist, Radiation Oncology, Community Practice (Northeast)
April 2, 2020

@Andrejs V. Strauss Update, April 2 2020. There is a new preprint https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v2.full.pdf of a randomized study from China involving 62 patients that found improved clinical outcomes in patients taking hydroxychloroquine (HCQ) 200 mg BID for five days plus standard therapy vs standard therapy alone. All patients had moderate disease defined as confirmed COVID-19 infection, CT evidence of pneumonia, and  SaO2/SPO2 ratio > 93%. After six days, there was significant improvement in the lung CT's of the experimental group, improved time to clinical recovery as measured by cough and fever, and most importantly, four patients in the control group progressed to severe disease, whereas none of the experimental group did.

There was even a statement supporting the prophylactic use of HCQ. on a survey: "we found that none of our 80 SLE patients who took long-term oral HCQ had been confirmed to have SARS-CoV-2 infection or appeared to have related symptoms." The main limitations to this study was that standard therapy was not controlled nor well defined (oxygen therapy, antiviral agents, antibacterial agents, and immunoglobulin, with or without corticosteroids). The use of convalescent immunoglobulins from recovered COVID-19 patients is common in China, unlike the US. Based on the Ebola experience, it is likely that convalescent immunoglobulins will turn out to be the most effective single agent. So really this was a study of HCQ used as an adjunct to immunoglobulin therapy. Nonetheless, it is still the best evidence to date supporting HCQ, in moderate COVID-19 disease. 

To put this in perspective, the mortality curves from Italy, Spain, and France are all following the same shape, even though Italy predated the use of HCQ. Thus, HCQ is not a wonder drug. It has been hypothesized that the reason the death curve in Italy is flattening is due to a majority of the population having been infected. The virus is running out of unexposed people to infect. https://talkingpointsmemo.com/edblog/this-is-very-important-from-italy-please-read 

, Professor, Academic Institution (South)
April 2, 2020

Not a great study for the reasons you point out. Data should be coming out fairly soon from Europe and the US.

As a rheumatologist, I fear for our lupus patients experiencing shortage. HCQ is the base drug for all SLE patients if there are no contraindications, as it decreases odds of flare. Many of our patients, especially underinsured, depend on this drug, and shortage will increase use/dose of steroids with consequent adverse events and possibly increased risk for COVID.

I hope production steps up.


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