Antibiotic may kill cancer cell in melanoma

This report has a bit more intel:  https://nieuws.kuleuven.be/en/content/2021/antibiotics-may-help-to-treat-melanoma

And this is the abstract of the study on which the link you posted and the one above are based:  https://rupress.org/jem/article-abstract/218/9/e20210571/212494/Activation-of-the-integrated-stress-response

A couple of issues:

1. This work was done only in mice – not people with melanoma.
2. It is not absolutely clear which antibiotics they are talking about.  I could speculate, but….
3. Taking antibiotics, at least before embarking on immunotherapy, has proven to be detrimental in the response melanoma patients can attain.

Here are some reports about that:

Antibiotic use may decrease the effectiveness of immunotherapy – Feb 2017:  https://chaoticallypreciselifeloveandmelanoma.blogspot.com/2017/02/antibiotic-use-may-decrease.html

This – Decreased progression free survival in melanoma patients treated prior to or at start of immunotherapy – from 2019:  https://chaoticallypreciselifeloveandmelanoma.blogspot.com/2019/04/decreased-progression-free-survival-in.html

And, from within another 2019 post – https://chaoticallypreciselifeloveandmelanoma.blogspot.com/2019/08/antibiotics-gut-microbiome-and-heavier.html – I shared this:

<u>Effect of antibiotic exposure in patients with metastatic melanoma treated with PD-1 inhibitor or CTLA-4 inhibitor or a combination of both. </u> 2019 ASCO. Kapoor, Runnels, Boyce, et al.  J Clin Oncol 37, 2019 (suppl; abstr e14141)

Background: Pre clinical studies have demonstrated the effect of gut microbiome in the efficacy of immune check point inhibitors. The effect of antibiotic exposure to patients receiving PD-1/CTLA-4 inhibitor therapy has not been extensively studied, especially in metastatic melanoma. In this study, we demonstrate the effect of antibiotic exposure to metastatic melanoma patients receiving PD-1/CTLA-4 inhibitor therapy. Methods: We performed aretrospective analysis of 108 patients with stage 4 metastatic melanoma who received immunotherapy with PD-1 inhibitors or CTLA-4 inhibitors or combination of both between Nov 2010 and Oct 2017. Patients were divided into Abx(+) and Abx(-) groups that were defined as patients exposed or not exposed to antibiotics respectively. The time frame for antibiotic exposure was taken from 6 months prior to 1 month after initiation of immunotherapy. We compared progression free survival (PFS), overall survival (OS) and response rate (RR) between the two groups. RR was calculated based on the entire length of follow-up.  Results: Out of 108 patients, 66 were men, with a mean age 64.6 ± 15.1 years. 46 patients were exposed to antibiotics of varied classes. Median PFS in abx(+) group [88 days] was shorter as compared to abx(-) group [322 days].Patients in abx(-) group had a 68% reduced risk of progression within 200 days of immunotherapy initiation adjusting for sex, age and number of immunotherapy cycles . Median OS in ab(+) group [294 days] was shorter as compared to abx(-) group [573 days]. Response rate defined as percentage of patients whose cancer was stable or entered remission was 12.9% in abx(-) group as compared to 8.7% ab(+) group. Patients in abx(-) group had a 52% reduced risk of death adjusting for sex, age and number of immunotherapy cycles. Conclusions: Antibiotic exposure is associated with poorer outcomes in patients with advanced metastatic melanoma being treated with PD-1/CTLA-4 inhibitors which is likely related to alteration of gut microbiome. Antibiotics should be prescribed with caution in patients undergoing treatment with immune check point inhibitors. These data should be validated in a larger patient population.

<br style=”font-weight: 400;” />In this retrospective study of 108 melanoma patients treated with immunotherapy, it was noted that 46 were given antibiotics at some point between 6 months prior and 1 month after starting their immunotherapy treatment.  PFS was 88 days in those who took antibiotics and 322 days in the group who didn’t.  OS was 294 days in the antibiotic group – 573 days in the non-antibiotic group.  Response rate was 8.7% in the group that had taken antibiotics vs 12.9% in the group that had not been exposed to antibiotics.  As I wrote in the post I put up in April:  “So…if you really NEED antibiotics, they may save your life and will certainly decrease misery. BUT, if you DON’T really NEED them…they can cause harm, in lots of ways.”<br style=”font-weight: 400;” /><br style=”font-weight: 400;” />Now, there’s this:<br style=”font-weight: 400;” /><br style=”font-weight: 400;” />
<p style=”font-weight: 400;”><u>Cumulative Antibiotic Use Significantly Decreases Efficacy of Checkpoint Inhibitors in Patients with Advanced Cancer.</u>  Tinsley, Zhou, Tan, et al.  Oncologist. 2019 Jul 10.</p>
With the advent of immunotherapy, substantial progress has been made in improving outcomes for patients with advanced cancer. However, not all patients benefit equally from treatment, and confounding immune-related issues may have an impact. Several studies suggest that antibiotic use (which alters the gut microbiome) may result in poorer outcomes for patients treated with immune checkpoint inhibitors (ICI).
<h4>This is a large, single-site retrospective review of n = 291 patients with advanced cancer treated with ICI (n = 179 melanoma, n = 64 non-small cell lung cancer, and n = 48 renal cell carcinoma). Antibiotic use (both single and multiple courses/prolonged use) during the periods 2 weeks before and 6 weeks after ICI treatment was investigated.</h4>
Within this cohort, 92 patients (32%) received antibiotics. Patients who did not require antibiotics had the longest median progression-free survival (PFS), of 6.3 months, and longest median overall survival (OS), of 21.7 months. With other clinically relevant factors controlled, patients who received a single course of antibiotics had a shorter median OS (median OS, 17.7 months), and patients who received multiple courses or prolonged antibiotic treatment had the worst outcomes overall (median OS, 6.3 months). Progression-free survival times were similarly affected.

This large, multivariate analysis demonstrated that antibiotic use is an independent negative predictor of PFS and OS in patients with advanced cancer treated with ICIs. This study highlighted worse treatment outcomes from patients with cumulative (multiple or prolonged courses) antibiotic use, which warrants further investigation and may subsequently inform clinical practice guidelines advocating careful use of antibiotics.

Antibiotic use is negatively associated with treatment outcomes of immune checkpoint inhibitors (ICI) in advanced cancer. Cumulative antibiotic use is associated with a marked negative survival outcome. Judicious antibiotic prescribing is warranted in patients receiving treatment with ICI for treatment of advanced malignancy.

<br style=”font-weight: 400;” />Granted none of the patients in this study had melanoma.  And, as I noted above, if you need antibiotics, they can be essential and life saving.  But – if they are not required – they may cause us more harm than good.

Then there are these reports from earlier this year:  The gut microbiome again – as it relates to immunotherapy for melanoma, other cancers, antibiotic use, and fecal transplants! –  https://chaoticallypreciselifeloveandmelanoma.blogspot.com/2020/08/the-gut-microbiome-again.html  

Now, just to complicate things further – back in the 2013 – I reported a study that showed doxycycline – an old well known antibiotic – killed melanoma (albeit in the petri dish).  Here is that report:  https://chaoticallypreciselifeloveandmelanoma.blogspot.com/search?q=doxycycline

I don’t share all this to make things more confusing, but to show the importance of really figuring things out before subjecting real live melanoma patients to the whims of one researcher or pharmacology company.  Melanoma doesn’t make things easy.  There is soooooooooo much here that we do not begin to fully understand.   Do I hope that these ribosome attacking antibiotics will be the end of melanoma?  ABSOLUTELY!!!!!!!!!!!!!  Would I jump at the chance to take antibiotics when we are currently depending on immunotherapy to help us?  NOPE.  Not yet.

I have voiced many many many complaints about the way clinical trials work!!  Just put ‘clinical trial’ in the search bubble of my blog if you are interested.  And this is from someone who credits a phase 1 trial of Nivolumab (Opdivo) in 2010 with saving my life.  Still, with all the improvements clinical trials could use – they are still super important in getting us the treatments we need.

Hope this helps.  Thanks for sharing.  Every bit of melanoma news is important to discuss, think about, study, and watch for how it rolls out.  Take good care.  celeste