Colchicine is one example of a drug that interferes with cell division by acting on microtubule assembly and disassembly during mitosis. Such drugs (though not including colchicine) can and have been used as anticancer therapy to act directly on the tumor cells. The therapeutic margin is based on the fact that tumor cells divide more often than non-tumor cells. Unfortunately, a major limitation in the use of anti-mitotic drugs in cancer chemotherapy is their severe side effects. To make matters worse, many drugs (including colchicine) are substrates for transport out of the cancer cells by multidrug resistance (MDR) efflux pumps, such as P-glycoprotein and MRP, which are often overexpressed by tumor cells. As a result of this efflux, there is no therapeutic margin for these drugs.

Colchicine is one example of a drug that interferes with cell division by acting on microtubule assembly and disassembly during mitosis. Such drugs (though not including colchicine) can and have been used as anticancer therapy to act directly on the tumor cells. The therapeutic margin is based on the fact that tumor cells divide more often than non-tumor cells. Unfortunately, a major limitation in the use of anti-mitotic drugs in cancer chemotherapy is their severe side effects. To make matters worse, many drugs (including colchicine) are substrates for transport out of the cancer cells by multidrug resistance (MDR) efflux pumps, such as P-glycoprotein and MRP, which are often overexpressed by tumor cells. As a result of this efflux, there is no therapeutic margin for these drugs.

Adam has given us a well considered answer on this. But I would like us to point out that if we look a bit further we will find the constructs currently used in colchicine studies like this one: http://www.bradford.ac.uk/life-sciences/news-and-events/news/new-cancer-treatment-to-target-all-solid-tumours.php. Perhaps there is something we've overlooked that these researchers are finding hopeful in using cochicine in the arsenal against the virtual tidal wave of cancers of all types that we are witnessing throughout the world today, and most especially the United States where cancer rates are ostensibly the highest of all advanced nations.. 

Colchicine is routinely used as therapy for Acute Gout attacks, the way of dosing was: 'Up to an effect showing or up to diarrea appearing, what comes first', on any of this happening, the Colchicine should be discontinued, and also in a chronic way, 1 mg od, for conditions such as Pseudogout, however, Colchicine toxicity is potentially lethal, and as it's a genotoxic agent, it should probably be banned for use in any woman with any childbearing possibility, even recent menopausals, and the use in men probably needs a discussion with the patient about the genomic risks of this drug, as an old Spanish proverb said that: 'Men lose early teeth than seed' -seed meaning the semen, the ability to make a woman pregnant-

The importance of the potential genotoxic effect leading to problems in the offspring of persons currently of previously on this Drug has probably never been specifically addressed, but from underground publications, it's known that the use of Colchicine injections in the shaft of Cannabis plants was a known way to increase the Cannabinoids' contents of the plant, and this represents an importat genome effect, mediated perhaps in this 'herbal' case by Colchicine induced polyploidia.

When visiting a Medical Lab decades ago, one of the physicians there spontaneously reported to me that they were having good results in Rheuma-like disorders or symptoms in perimenopausal women, by prescribing low Colchicine doses in a 1 mg od continuous therapy.

Stimulated by this information, I prescribed to a few post menopausal women attending my office and suffering: 'Dry Eye Syndrome', 1 mg Colchicine od in a continuous way, no Schirmer or other objective assessment test was performed ever, but some of the few women treated this ways reported a subjective improvement in the Ocular symptoms after a while on Colchicine,

I discontinued prescribing the drug to all of my patients with the exception of those having Pseudogout, when one of the women showed a Neutropenia, that even when Absolute Leucocyte Count was over 3'000/ ul, this would have eventually allowed dosing any Cancer ChemoTherapy to this person, this is not the kind of Lab result that would keep everybody comfortable.

From other literature reports a putative effect of Colchicine may be suspected in Alzheimer's disease, Colchicine having an action on Amyloid substance in Amyloidosis, an Ig chain deposition disease, and thus, Colchicine having a depolymerization effect on proteins, the deposits of proteins in the brain of Alzheimer disease, or perhaps more specifically in those suffering from Lewy Bodies dementia, may deserve some formal in vitro or Clinical testing.

As another anecdote; I was told by an acquaintance that wanted to get rid of some unpleasant hosts at his home, that he gave them a Colchicine loaded mushrooms' omelette (he probably obtained the Colchicine in a pharmacy without a prescription, you can buy almost anything but WHO specially controlled substances without any medical document here in Spain), and shortly before when the Colchicine Diarrhea started, he warned them that he was not 100% sure about all of the mushrooms in the omelette not being poisonous. After the warning of an intentional intoxication, the hosts left the place, but this may be a legal offense, this is like a poisoning, and a woman in one the North-African Spanish towns was sentenced to jail when she gave her husband a dose of Carbimide or other Antabus-effect drug, that is used for Alcohol dependence desintoxication, as those who drink Alcohol while on this class of drugs develop very nuisant symptoms, as red face, tachycardia, heart rhythm changes,...

Colchicine overdose may kill.

Thanks for your attention. Regards. Salut †

Thant you Mister Adam B Shapiro and Mister Max Stanley Chartrand for the response

I read some of these works, and what I mentioned in my question; that the molecules were modified and made inactive until it is contate in with the enzyme secreted by tumral cells, once activated, it destroys blood vessels supplying the tumor.

But the molecule is enabled and triggered to increased enzyme levels found in the tumor environment; therefore the activation is in a developed stage, or in the presence of large tumor mass;

And also,this activation can it touching the blood vessels supplying other healthy tissues? This is possible because the effect of the molecules is not always controllable; that why i'm asking why to not kill the tumor by causing apoptosis for example.

() it is only questions ................ Thank you 

Thank you Mister Joe Graymer for the informations 

ZD6126 is a phosphate prodrug derived from colchicine (via N-acetylcolchinol) and was investigated as a vascular-disrupting agent (VDA). It entered phase II trials however trials were stopped because of cardiotoxicity. More promising VDAs for cancer treatment are structurally related combretastatin derivatives such as fosbretabulin and ombrabulin.

As far as I know (and as far as I can see from my own compounds under investigation so far) a large number of VDAs selectively attack tumor blood vessels because these vessels are different from most normal blood vessels. Yet, indeed there is a problem of VDAs lacking cytotoxic activity in vivo. Thus, aside combination therapy, there are VDA molecules under investigation, which likewise induce tumor cell killing by apoptosis induction (verubulin) or ROS production (Combretastatin A1) in order to kill those few tumor cells which survive the vascular-disrupting effect (mainly those at the rim of tumor bodies).  

Compared with solely apoptosis-inducing agents (which can also attack and kill non-malignant cells), you can kill many more cancer cells by only a few VDA molecules which destroy the tumor blood vessel system and, thus, tumor supply, because most tumor cells of the affected tumor body die of starvation then. It is like warfare, destroy the supply of the enemy and he will surrender.

I'd say that for Vascular Disrupting Agents, timing and duration of dosing respect to a concomitant Chemo-Therapy matters, this was assessed by some in terms of Interstitial Fluid Pressure changes, that can be measured by a focused Nuclear Magnetic Resonance Imaging.

For the most known VDA, Bevacizumab, drug file's data differ about amount to dose for individual types of tumors, but sometimes, more was worse, also, good predictive markers seem being scarce, you can say that the presence of Ascites is good predictor for Bevazicumab response, but not much more, also, in CRC, location of primary tumor matters regarding responses to Bevacizumab, this is a field I'd like having a review and formal dose-finding studies, but not in the line of a Maximum Tolerated Dose, as in Phase I studies, but of minimal efficacious dose, and dose of maximal efficacy, and this may require expanding the size, complexity and cost of early phase trials, but the finding process may give you the serendipity surprise of lower doses being better from a clinical point of view.

As with any drug acting by modulating a complex system, the same as for Corticosteroids, the concepts of Elimination Half-Life and Half-Life of Biological Effect may differ, this having a weight in considering pattern of dosing.

I'm still disappointed in finding a reason for not dosing Corticosteroids in a od, early morning schedule, as both the drug Pharmaco-Kinetic plasma half-life and the Biological Effect half-life of Corticosteroids are longer than 24 h, but many times medical or other procedures have an important not well understood carry-over effect  in its way of use from early publications.

Colchicine is a geno-toxic, I won't use it in women in pregnancy age, and many would say that not in men, but it also can induce deadly toxicity in overdoses and not too high acute dosing.

In chronic use, there's some experience with a continued od dosing of 1 mg in Chondrocalcinosis, but the use of this Drug to treat cancer is scarce, most of its current applications are in inflammatory processes, perhaps specially in auto-immune ones.

There are more than numerous "anti-tubulin" drugs that are used more than efficiently to combat almost all types of cancers.

Anti-tubulin drugs are those drugs that ACTUALLY CURED the largest number of cancer patients.

There are several "anti-cancer drug tubulin-binding sites" and colchicine-related drugs are irreversible toxic drugs with no therapeutic margins in oncological treatment ... which is actually not the case with "certain" other 4th or 5th anti-tubulin generation drugs ...

I think that anyone who would like to "argument" in this oncology-related domain should have an in-depth reading of the attached articles.

All the best

Robert 

thank you to all of you