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"Melatonin and non-small cell lung cancer: new insights into signaling pathways"


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"the combined treatment with melatonin and chemotherapy may have a synergistic effect, as with some other tumors, leading to a prolonged survival and improved quality of life in patients with NSCLC."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521447/


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asafsh
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Thanks Johan for this article. 

had a look to another article referenced from there - oral doses from 10mg to 40mg was used:

Melatonin as Adjuvant Cancer Care With and Without Chemotherapy: A Systematic Review and Meta-analysis of Randomized Trials

pharmakinetics of melatonin is improved upon IV administration:

Clinical Pharmacokinetics of Melatonin: A Systematic Review

But i don't know, whether its plasma concentration needs to be increased further during radio/chemotherapy as Melatonin is regarded anti-oxidant and may reduce therapy efficacy. Giving the fact that melatonin in hundred milligram range is already used, live data sharing is much appreciated.

Another interesting point - co-administration of melatonin with caffeine increases its bioavailability (note the caffeine potentiated chemotherapy article):

Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity

Melatonin works in sarcoma tumors as well:

Melatonin: an anti-tumor agent for osteosarcoma

Unfortunately that requires mM level concentration when administered alone or 50-100uM when in combination with vincristine and ifosfamide (in-vitro).

And giving the fact that Melatonin (and Wogonin too) may downregulate the Cyclin D1 it is interesting to try it with MDM2 inhibitors as these both may work in synergy against many types of tumors:

Downregulation of cyclin D1 sensitizes cancer cells to MDM2 antagonist Nutlin-3

because of MDM2 antagonists are still in trial phase, natural plant mdm2 antagonists might be researched:

Natural products targeting the p53-MDM2 pathway and mutant p53: Recent advances and implications in cancer medicine

p.s. Melatonin may interact with NSAID (i remember opinion on nsaid administration at bed time, exactly same time as Melatonin is given) so may be better to space them in time or use together if desired cytotoxicity of both won't be impaired upon co-administration. May be Daniel may share his opinion on this subject:

https://www.researchgate.net/publication/331408103_Melatonin_as_an_armament_against_non-steroidal_anti-inflammatory_drug_induced_gastric_injury_An_overview

 


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asafsh
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BTW, there is a presentation paper from Riordan clinics for high dose Melatonin treatment:

High Dose Melatonin Therapy - An Ideal Adjuvant Anti-cancer Therapy

What is interesting - at the end it suggests 300mg Melatonin 2 hours before PET/CT.

Why? For contrast agent facilitated tumor cell influx, or synergy with PET/CT radiation induced ROS, or both?


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Posted by: @asafsh

 

Clinical Pharmacokinetics of Melatonin: A Systematic Review

 

Very useful! 


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Posted by: @asafsh

 

But i don't know, whether its plasma concentration needs to be increased further during radio/chemotherapy as Melatonin is regarded anti-oxidant and may reduce therapy efficacy. Giving the fact that melatonin in hundred milligram range is already used, live data sharing is much appreciated.

 

"Increased Survival Time in Brain Glioblastomas by a Radioneuroendocrine Strategy With Radiotherapy Plus Melatonin Compared to Radiotherapy Alone":  https://pubmed.ncbi.nlm.nih.gov/8570130/


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Melatonin + Aswagandha could be a good combination to enhance radiotherapy.

Radiosensitizing properties of ashwgandha: https://pubmed.ncbi.nlm.nih.gov/8225418/


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