8 ms·

Chemotherapy, Then and Now

120 points by apsec112 9y ago

lr4444lr 9y ago
Enjoyable read. Anyone know if she did a similar research review of concomitant temporary fasting during the pre-application and treatment periods of chemotherapy? Her blog is not searchable and a domain-specific Google search for relevant terms didn't turn up anything.
- ezekg 9y ago
  Luckily, most WordPress/SquareSpace blogs give you a link to a search page, or a search bar directly, on the 404 page: https://www.sarah-constantin.org/search https://www.sarah-constantin.org/search.
sowbug 9y ago
Why do so many modern cancer drug names end with the letter B?
- IvyMike 9y ago
  https://en.wikipedia.org/wiki/Drug_nomenclature https://en.wikipedia.org/wiki/Drug_nomenclature, https://www.medscape.com/viewarticle/867446_3 https://www.medscape.com/viewarticle/867446_3 TL;DR: -ab is related to antibody, -ib is related to inhibitors.
- agumonkey 9y ago
  these are immunotherapy drugs, ib means inhibitor and ab means antibody IIRC.
- pkaye 9y ago
  Drugs that end in mab are monoclonal anti-bodies. They are cloned copies of anti-bodies from various sources that target something in the body.
- mitchtbaum 9y ago
  Caution: etymologically-oriented answers generally miss important nominological / nymological / onomatological / onomastic foundations. This namespace is a "synthetic" social construction. It has interesting "quirks", "gotchas", and "zingers". https://en.wikipedia.org/wiki/Onomastics https://en.wikipedia.org/wiki/Onomastics https://en.wiktionary.org/wiki/onomatology https://en.wiktionary.org/wiki/onomatology https://en.wiktionary.org/wiki/nomen https://en.wiktionary.org/wiki/nomen https://en.wiktionary.org/wiki/-nym https://en.wiktionary.org/wiki/-nym http://messymatters.com/nominology/ http://messymatters.com/nominology/
- aviv 9y ago
  It's like .com domains. They're running out of good names. Ending with letter B is Big Pharma version of .io domains.
sgt101 9y ago
The obvious question is : given all of the facts presented why is a multi-billion industry stuffed with the finest minds and equipment that can be bought or found carry on in apparent defiance of reason? I see three explanations. First the pharma/cancer industry is a giant conspiracy working against the health and needs of cancer patients everywhere. Second, for some dreadful reason none of the brilliant minds working ceaselessly day and night have noticed these facts so far. They haven't read the studies and have been unable to parse the evidence, data science (counting) to the rescue. Third, there are other facts and knowledge which the author and readers external to the industry are not privy to, possibly because acquiring them required seven years of medical school followed by twenty years of biomedical research.
- Retric 9y ago
  I think 4 is a much larger issue. Cancer is hard, and low hanging fruit is easier to find. Also, adding 4 months of life when you're talking about something 40% of Americans are going to be diagnosed with really is a huge deal. Adding say 1 extra day of life to every cancer patient in the US would be the equivalent of saving ~25 lives each and every year.
  - tata1212 9y ago
    It's hard to talk about in aggregate because chemotherapy doesn't have the same effect on all types of cancers. I went through it. Aside from whatever months it added, it took about 3 of them away because I wasn't doing anything other than barfing, chugging hydrocodone syrup, and sleeping for that time period.
    - tata1212 9y ago
      I should also add that I clearly wasn't getting the worst of it. Breast cancer patients seemed to have 6+ months vs my 3+ months for my adenocarcinoma. Also, I didn't lose my hair, finger nails, etc. It was, though, 3+ months lost to nausea, hydrocodone fog, pain, and sleep.
  - edflsafoiewq 9y ago
mitchtbaum 9y ago
> Its results are distinctly unimpressive... So far as I can tell, where there has been improvement in cancer mortality since the 1970’s, it is mostly due to people smoking less, early detection of some kinds of cancer, and adjuvant (cytotoxic) chemotherapy, not to targeted chemotherapies. I'll just add this quote for a starting point from such abject failure, "The first step towards wisdom is to call things by their right name." -Confucius "what's cancer?", "how do you fix it?", don't ask them.
kyberias 9y ago
I think the text contrast couldn't be any worse.
iskander 9y ago
>Targeted chemotherapy consists of drugs that are meant to specifically kill cancer cells and not healthy cells. Putting immunotherapies (like nivolumab) under this category I think will only confuse the reader about the state (and direction) of oncology. Nivolumab doesn't target cancer cells, it blocks an inhibitory receptor on T-cells, which then kill cancer cells more readily. It's been approved for a wide range of cancer types since it's really a treatment of the immune system: https://www.drugs.com/history/opdivo.html https://www.drugs.com/history/opdivo.html Approvals to date: melanoma, lung cancer, kidney cancer, hodgkin lymphoma, head and neck cancer, bladder cancer, MSI-H colorectal cancer. The distinction between targeted therapies and immunotherapies is very important since, aside from different mechanism, they also tend to have very different trajectories of relapse/resistance. Any metastatic cancer is essentially guaranteed to become resistant to a targeted therapy within 6-18 months. Drugs like nivolumab, on the other hand, offer a minority of patients (10-40% depending on the cancer) a chance at durable responses (cancers either cured or prevented from spreading by immune surveillance).
- adrianm 9y ago
  I am being treated with pembrolizumab for metastatic MSI-H CRC (I'm in my late 20s). Last year the cancer rapidly metastasized further, covering my abdomen in tumors. Prognosis was not good to say the least. It took around 12 weeks for the treatment to "kick in", but at that point tumor regression became rapid. Every CT scan since has shown significant reduction in the abdominal tumors until my last one a few weeks ago; there is no longer any sign of cancer in my abdomen. Overall, it went from "countless" visible tumors ranging from a few mm to several cms each in size, to nothing visible on CT today. o_O Who knows what the future will bring. I'm trying to be optimistic but I'm also realistic about the statistics here. However, going from my literal death bed where I was in horrible pain suffering for 24 hours a day to quasi-normalcy in a matter of several months blows my mind when I think about it. It did give me horrible colitis (yay for autoimmune side-effects!), but I'll take that over a painful death any day of the week. The colitis is bad enough that they had to discontinue the treatment for a while. tldr; Science rules. Side effects suck. And a sincere thank you to anyone reading who is or was ever involved in cancer research.
legulere 9y ago
The article sounds pretty negative, but if you look at 5 year survival rates for cancer you see slow but steady progress: https://pancreaticcanceraction.org/wp-content/uploads/2012/10/Trends-in-cancer-survival-by-tumour-site-1971_2011-1000x570.png https://pancreaticcanceraction.org/wp-content/uploads/2012/1...
- whoisjuan 9y ago
  Hmm, but no progress in pancreatic. That one seems pretty lethal.
- dennis_jeeves 9y ago
  The steady 'progress' is not what it seems. Improved and earlier detection of cancer means that a patient will survive for significantly longer after the detection past the 5 year mark. Several decades ago the patient would die relatively quickly between the period of detection and within the 5 year period. As one of the posters ( reasonattlm )pointed out,cancer can be regarded as one of the diseases of aging. To kill cancer cells will not improve things beyond a point because the body will produce more. I would speculate if detection methods we sufficiently sensitive, we would _all_ have some cancer cells within us. It is a matter of degree. Summary: Except of a few types of cancer, the treatment has not improved the outcome for cancer patience during the past few decades. Also remember: lies, damn lies and statistics. My sources: A non-mainstream cancer doctor ( but is a conventional MD ) who was widely regarded as a quack, by the mainstream medical community. Heresy is not tolerated well.
dnautics 9y ago
> (Normally we associate decentralization with freedom; but consolidating authority in a small number of people rather than a bureaucratic process can make it easier to get things done quickly and iterate.) I would hardly call 'bureaucratic process' decentralization.
liveoneggs 9y ago
this is strange since I watched my mother take medicine and survive (trial-to-trial) for over ten years without any traditional chemotherapy, which she wanted to avoid at all costs. A clerical error meant she missed the next trial and.. anyway that was that. A friend's dad currently has stage 4 lung cancer and has been taking a daily pill for over two years now and just surviving without any of the traditional chemotherapy issues. These pills are amazing but I guess your luck eventually runs out.
paulie_a 9y ago
I have a close friend's mother with lung cancer that is currently being treated with an experimental drug. After reading the "no difference" multiple times I am not too optimistic. I do not know which drug she is taking but :(
beefman 9y ago
> Part of this is due to the fact that many of these are drugs for refractory or late-stage cancer; this in turn may be due to regulatory or medical-ethics issues that make it hard to directly compare a new drug to the standard-of-care old drugs. My best friend's younger brother is currently dying of sarcoma. I think it should be illegal to give therapies (and false hope) which are proven to extend agony and proven not to extend overall survival. Meanwhile, studies of new therapies must be performed on relapsed patients with hardened cancers. As long as this is true, the rate of discovery of effective therapies will remain staggeringly low, and the rate of human suffering from cancer staggeringly high. It's easy to blame regulations, but in my opinion they are ultimately a consequence of our inability to speak honestly. People I've known all my life, through thick and thin... yet it seems impossible for us to acknowledge the truth of his treatment: progressively increasing suffering and death, at tremendous financial cost to his family and society. I recently forced myself to break the ice a bit in a conversation with a mutual friend. It was harder than I imagined but went better than I thought it would. Paul Erdos had a way of talking extremely honestly about things... I tried to channel him a bit. I encourage everything to think hard about breaking the status quo of discourse about cancer. I'm left wondering whether, if I get cancer, I will have the ability to choose experimental treatment in lieu of "protocols" which are proven to be unsafe and ineffective. (If anyone has advice on that, I'd like to start getting a plan together.) Background: My parents were both pharmaceutical chemists. My father is named on over 40 patents. I invest in pharmaceutical and "biotech" companies with a focus on new cancer therapies.
- specialist 9y ago
  "I think it should be illegal to give therapies (and false hope) which are proven to extend agony and proven not to extend overall survival." I used to agree with you, emphatically. Now I'm not so sure. I had a bone marrow transplant 30 years ago. At the time, one year mortality was 95%. Let's just say it was hard, both physically and mentally. And the doctors absolutely lied by omission. I see that look of hopeful desperation in new patients every time I go back for a checkup. No doubt patients (research subjects) are being exploited. But... Whereas I was a boy in the bubble, similar treatment today is practically an outpatient therapy. Like a comment upthread, one of my bffs was diagnosed with terminal cancer, qualified for a clinical trial for immunotherapy, now three years later is "cancer free". Seeing how far we've progressed, now I think our sacrifices were probably worth it. I'm certainly less angry about it.
dm319 9y ago
Here is a nice figure on cancer survival changes from 1971 to 2011[1]. The writer is correct that not all of this improvement is down to newer drugs - a lot of it is down to better 'supportive' management - recognising side effects of chemo, keeping on top of transfusions, having cancer centres where all of this can be coordinated, having specialists (oncologists) managing the disease etc etc. For example, the survival of acute myeloid leukaemia has improved dramatically since then, but our treatment has remained the same two old-fashioned drugs. Also the writer lumps chemo drugs into two categories - cancer chemotherapy, and targeted therapies. That is probably not a good way to look at it as iskander has already mentioned re: immune checkpoint therapy, which is quite different. Other categories include: * small molecule drugs (not antibodies, target a cell metabolic pathway) * adoptive cell therapy - grafting antibodies to killer immune cells etc etc... Progression-free survival isn't as good a metric as overall survival - that is true. It was brought in as a replacement for some other indicators, such as relapse-free survival, which ignored everything (including death due to treatment) except relapse. Progression free survival doesn't let you get away with that. Some diseases have been changed massively by treatment. CML used to have an overall survival of around 5-7 years, it's now so long we can't really measure it since imatinib was brought it. Obviously people do die of the disease, but we don't know what the average life expectancy is because they are doing pretty well. To introduce new treatments in this disease you're going to have to use another metric apart from overall survival. [1] http://www.cancerresearchuk.org/sites/default/files/styles/cruk_wide_resp_breakpoint_one/public/cs_surv_trends.png?itok=0LfcIZ84 http://www.cancerresearchuk.org/sites/default/files/styles/c...
scythe 9y ago
I'm a bit surprised that we're only looking at the results of targeted therapy in late-stage cancer. It seemed apparent to me from the name that targeted therapies were supposed to be less toxic, so they could be used in patients who weren't effectively dead, i.e., in earlier-stage cancers. Late-stage malaria and tuberculosis have terrible survival rates, and those are diseases we're supposed to be good at treating.

120 points by apsec112 9y ago

Enjoyable read. Anyone know if she did a similar research review of concomitant temporary fasting during the pre-application and treatment periods of chemotherapy? Her blog is not searchable and a domain-specific Google search for relevant terms didn't turn up anything.

ezekg 9y ago
Luckily, most WordPress/SquareSpace blogs give you a link to a search page, or a search bar directly, on the 404 page: https://www.sarah-constantin.org/search https://www.sarah-constantin.org/search.

sowbug 9y ago

Why do so many modern cancer drug names end with the letter B?

IvyMike 9y ago
https://en.wikipedia.org/wiki/Drug_nomenclature https://en.wikipedia.org/wiki/Drug_nomenclature, https://www.medscape.com/viewarticle/867446_3 https://www.medscape.com/viewarticle/867446_3 TL;DR: -ab is related to antibody, -ib is related to inhibitors.
agumonkey 9y ago
these are immunotherapy drugs, ib means inhibitor and ab means antibody IIRC.
pkaye 9y ago
Drugs that end in mab are monoclonal anti-bodies. They are cloned copies of anti-bodies from various sources that target something in the body.
mitchtbaum 9y ago
Caution: etymologically-oriented answers generally miss important nominological / nymological / onomatological / onomastic foundations. This namespace is a "synthetic" social construction. It has interesting "quirks", "gotchas", and "zingers". https://en.wikipedia.org/wiki/Onomastics https://en.wikipedia.org/wiki/Onomastics https://en.wiktionary.org/wiki/onomatology https://en.wiktionary.org/wiki/onomatology https://en.wiktionary.org/wiki/nomen https://en.wiktionary.org/wiki/nomen https://en.wiktionary.org/wiki/-nym https://en.wiktionary.org/wiki/-nym http://messymatters.com/nominology/ http://messymatters.com/nominology/
aviv 9y ago
It's like .com domains. They're running out of good names. Ending with letter B is Big Pharma version of .io domains.

sgt101 9y ago

The obvious question is : given all of the facts presented why is a multi-billion industry stuffed with the finest minds and equipment that can be bought or found carry on in apparent defiance of reason? I see three explanations. First the pharma/cancer industry is a giant conspiracy working against the health and needs of cancer patients everywhere. Second, for some dreadful reason none of the brilliant minds working ceaselessly day and night have noticed these facts so far. They haven't read the studies and have been unable to parse the evidence, data science (counting) to the rescue. Third, there are other facts and knowledge which the author and readers external to the industry are not privy to, possibly because acquiring them required seven years of medical school followed by twenty years of biomedical research.

Retric 9y ago
I think 4 is a much larger issue. Cancer is hard, and low hanging fruit is easier to find. Also, adding 4 months of life when you're talking about something 40% of Americans are going to be diagnosed with really is a huge deal. Adding say 1 extra day of life to every cancer patient in the US would be the equivalent of saving ~25 lives each and every year.
- tata1212 9y ago
  It's hard to talk about in aggregate because chemotherapy doesn't have the same effect on all types of cancers. I went through it. Aside from whatever months it added, it took about 3 of them away because I wasn't doing anything other than barfing, chugging hydrocodone syrup, and sleeping for that time period.
  - tata1212 9y ago
    I should also add that I clearly wasn't getting the worst of it. Breast cancer patients seemed to have 6+ months vs my 3+ months for my adenocarcinoma. Also, I didn't lose my hair, finger nails, etc. It was, though, 3+ months lost to nausea, hydrocodone fog, pain, and sleep.
- edflsafoiewq 9y ago

mitchtbaum 9y ago

> Its results are distinctly unimpressive... So far as I can tell, where there has been improvement in cancer mortality since the 1970’s, it is mostly due to people smoking less, early detection of some kinds of cancer, and adjuvant (cytotoxic) chemotherapy, not to targeted chemotherapies. I'll just add this quote for a starting point from such abject failure, "The first step towards wisdom is to call things by their right name." -Confucius "what's cancer?", "how do you fix it?", don't ask them.

kyberias 9y ago

I think the text contrast couldn't be any worse.

iskander 9y ago

>Targeted chemotherapy consists of drugs that are meant to specifically kill cancer cells and not healthy cells. Putting immunotherapies (like nivolumab) under this category I think will only confuse the reader about the state (and direction) of oncology. Nivolumab doesn't target cancer cells, it blocks an inhibitory receptor on T-cells, which then kill cancer cells more readily. It's been approved for a wide range of cancer types since it's really a treatment of the immune system: https://www.drugs.com/history/opdivo.html https://www.drugs.com/history/opdivo.html Approvals to date: melanoma, lung cancer, kidney cancer, hodgkin lymphoma, head and neck cancer, bladder cancer, MSI-H colorectal cancer. The distinction between targeted therapies and immunotherapies is very important since, aside from different mechanism, they also tend to have very different trajectories of relapse/resistance. Any metastatic cancer is essentially guaranteed to become resistant to a targeted therapy within 6-18 months. Drugs like nivolumab, on the other hand, offer a minority of patients (10-40% depending on the cancer) a chance at durable responses (cancers either cured or prevented from spreading by immune surveillance).

adrianm 9y ago
I am being treated with pembrolizumab for metastatic MSI-H CRC (I'm in my late 20s). Last year the cancer rapidly metastasized further, covering my abdomen in tumors. Prognosis was not good to say the least. It took around 12 weeks for the treatment to "kick in", but at that point tumor regression became rapid. Every CT scan since has shown significant reduction in the abdominal tumors until my last one a few weeks ago; there is no longer any sign of cancer in my abdomen. Overall, it went from "countless" visible tumors ranging from a few mm to several cms each in size, to nothing visible on CT today. o_O Who knows what the future will bring. I'm trying to be optimistic but I'm also realistic about the statistics here. However, going from my literal death bed where I was in horrible pain suffering for 24 hours a day to quasi-normalcy in a matter of several months blows my mind when I think about it. It did give me horrible colitis (yay for autoimmune side-effects!), but I'll take that over a painful death any day of the week. The colitis is bad enough that they had to discontinue the treatment for a while. tldr; Science rules. Side effects suck. And a sincere thank you to anyone reading who is or was ever involved in cancer research.

legulere 9y ago

The article sounds pretty negative, but if you look at 5 year survival rates for cancer you see slow but steady progress: https://pancreaticcanceraction.org/wp-content/uploads/2012/10/Trends-in-cancer-survival-by-tumour-site-1971_2011-1000x570.png https://pancreaticcanceraction.org/wp-content/uploads/2012/1...

whoisjuan 9y ago
Hmm, but no progress in pancreatic. That one seems pretty lethal.
dennis_jeeves 9y ago
The steady 'progress' is not what it seems. Improved and earlier detection of cancer means that a patient will survive for significantly longer after the detection past the 5 year mark. Several decades ago the patient would die relatively quickly between the period of detection and within the 5 year period. As one of the posters ( reasonattlm )pointed out,cancer can be regarded as one of the diseases of aging. To kill cancer cells will not improve things beyond a point because the body will produce more. I would speculate if detection methods we sufficiently sensitive, we would _all_ have some cancer cells within us. It is a matter of degree. Summary: Except of a few types of cancer, the treatment has not improved the outcome for cancer patience during the past few decades. Also remember: lies, damn lies and statistics. My sources: A non-mainstream cancer doctor ( but is a conventional MD ) who was widely regarded as a quack, by the mainstream medical community. Heresy is not tolerated well.

dnautics 9y ago

> (Normally we associate decentralization with freedom; but consolidating authority in a small number of people rather than a bureaucratic process can make it easier to get things done quickly and iterate.) I would hardly call 'bureaucratic process' decentralization.

liveoneggs 9y ago

this is strange since I watched my mother take medicine and survive (trial-to-trial) for over ten years without any traditional chemotherapy, which she wanted to avoid at all costs. A clerical error meant she missed the next trial and.. anyway that was that. A friend's dad currently has stage 4 lung cancer and has been taking a daily pill for over two years now and just surviving without any of the traditional chemotherapy issues. These pills are amazing but I guess your luck eventually runs out.

paulie_a 9y ago

I have a close friend's mother with lung cancer that is currently being treated with an experimental drug. After reading the "no difference" multiple times I am not too optimistic. I do not know which drug she is taking but :(

beefman 9y ago

> Part of this is due to the fact that many of these are drugs for refractory or late-stage cancer; this in turn may be due to regulatory or medical-ethics issues that make it hard to directly compare a new drug to the standard-of-care old drugs. My best friend's younger brother is currently dying of sarcoma. I think it should be illegal to give therapies (and false hope) which are proven to extend agony and proven not to extend overall survival. Meanwhile, studies of new therapies must be performed on relapsed patients with hardened cancers. As long as this is true, the rate of discovery of effective therapies will remain staggeringly low, and the rate of human suffering from cancer staggeringly high. It's easy to blame regulations, but in my opinion they are ultimately a consequence of our inability to speak honestly. People I've known all my life, through thick and thin... yet it seems impossible for us to acknowledge the truth of his treatment: progressively increasing suffering and death, at tremendous financial cost to his family and society. I recently forced myself to break the ice a bit in a conversation with a mutual friend. It was harder than I imagined but went better than I thought it would. Paul Erdos had a way of talking extremely honestly about things... I tried to channel him a bit. I encourage everything to think hard about breaking the status quo of discourse about cancer. I'm left wondering whether, if I get cancer, I will have the ability to choose experimental treatment in lieu of "protocols" which are proven to be unsafe and ineffective. (If anyone has advice on that, I'd like to start getting a plan together.) Background: My parents were both pharmaceutical chemists. My father is named on over 40 patents. I invest in pharmaceutical and "biotech" companies with a focus on new cancer therapies.

specialist 9y ago
"I think it should be illegal to give therapies (and false hope) which are proven to extend agony and proven not to extend overall survival." I used to agree with you, emphatically. Now I'm not so sure. I had a bone marrow transplant 30 years ago. At the time, one year mortality was 95%. Let's just say it was hard, both physically and mentally. And the doctors absolutely lied by omission. I see that look of hopeful desperation in new patients every time I go back for a checkup. No doubt patients (research subjects) are being exploited. But... Whereas I was a boy in the bubble, similar treatment today is practically an outpatient therapy. Like a comment upthread, one of my bffs was diagnosed with terminal cancer, qualified for a clinical trial for immunotherapy, now three years later is "cancer free". Seeing how far we've progressed, now I think our sacrifices were probably worth it. I'm certainly less angry about it.

dm319 9y ago

Here is a nice figure on cancer survival changes from 1971 to 2011[1]. The writer is correct that not all of this improvement is down to newer drugs - a lot of it is down to better 'supportive' management - recognising side effects of chemo, keeping on top of transfusions, having cancer centres where all of this can be coordinated, having specialists (oncologists) managing the disease etc etc. For example, the survival of acute myeloid leukaemia has improved dramatically since then, but our treatment has remained the same two old-fashioned drugs. Also the writer lumps chemo drugs into two categories - cancer chemotherapy, and targeted therapies. That is probably not a good way to look at it as iskander has already mentioned re: immune checkpoint therapy, which is quite different. Other categories include: * small molecule drugs (not antibodies, target a cell metabolic pathway) * adoptive cell therapy - grafting antibodies to killer immune cells etc etc... Progression-free survival isn't as good a metric as overall survival - that is true. It was brought in as a replacement for some other indicators, such as relapse-free survival, which ignored everything (including death due to treatment) except relapse. Progression free survival doesn't let you get away with that. Some diseases have been changed massively by treatment. CML used to have an overall survival of around 5-7 years, it's now so long we can't really measure it since imatinib was brought it. Obviously people do die of the disease, but we don't know what the average life expectancy is because they are doing pretty well. To introduce new treatments in this disease you're going to have to use another metric apart from overall survival. [1] http://www.cancerresearchuk.org/sites/default/files/styles/cruk_wide_resp_breakpoint_one/public/cs_surv_trends.png?itok=0LfcIZ84 http://www.cancerresearchuk.org/sites/default/files/styles/c...

scythe 9y ago

I'm a bit surprised that we're only looking at the results of targeted therapy in late-stage cancer. It seemed apparent to me from the name that targeted therapies were supposed to be less toxic, so they could be used in patients who weren't effectively dead, i.e., in earlier-stage cancers. Late-stage malaria and tuberculosis have terrible survival rates, and those are diseases we're supposed to be good at treating.