Comments on: Cancer Patients Try Experimental Meds In The UK http://www.pharmalot.com/2008/04/cancer-patients-try-experimental-meds-in-the-uk/ News, Comment and Conversation Fri, 10 Feb 2012 21:03:03 +0000 http://wordpress.org/?v=2.6.2 By: Mark http://www.pharmalot.com/2008/04/cancer-patients-try-experimental-meds-in-the-uk/#comment-294637 Mark Sat, 19 Apr 2008 02:20:13 +0000 http://www.pharmalot.com/2008/04/cancer-patients-try-experimental-meds-in-the-uk/#comment-294637 I'd like to clarify a few things about clinical trials for oncology agents. For cytotoxic drugs, clinical trails are conducted in patients. However, for drugs such as the RTK inhibitors, some clinical trials are conducted in healthy volunteers. These trials would be mainly conducted in order to understand the PK of the drug in a human population in which disease of concomitant medications would not have an impact on the PK of the drug. For example, the first clinical trial with sunitinib was conducted in healthy volunteers. Nine subjects were administered a 50 mg dose. Studies to assess the effect of food, ketoconazole or rifampin on the PK of sunitinib were also conducted in healthy subjects (15, 27 and 28, respectively). The SBA for Sutent shows at least 8 trials enrolling 117 healthy subjects. Healthy volunteer studies were also conducted for sorafenib, lapatinib and imatinib. Also, the initial clinical trial is often conducted in "all comers" unless there is a clear scientific rationale as to why the drug would work in a specific cancer only. An example of a drug using this approach was Velcade. I’d like to clarify a few things about clinical trials for oncology agents. For cytotoxic drugs, clinical trails are conducted in patients. However, for drugs such as the RTK inhibitors, some clinical trials are conducted in healthy volunteers. These trials would be mainly conducted in order to understand the PK of the drug in a human population in which disease of concomitant medications would not have an impact on the PK of the drug. For example, the first clinical trial with sunitinib was conducted in healthy volunteers. Nine subjects were administered a 50 mg dose. Studies to assess the effect of food, ketoconazole or rifampin on the PK of sunitinib were also conducted in healthy subjects (15, 27 and 28, respectively). The SBA for Sutent shows at least 8 trials enrolling 117 healthy subjects. Healthy volunteer studies were also conducted for sorafenib, lapatinib and imatinib.

Also, the initial clinical trial is often conducted in “all comers” unless there is a clear scientific rationale as to why the drug would work in a specific cancer only. An example of a drug using this approach was Velcade.

]]> By: Former pharma Marketing Exec http://www.pharmalot.com/2008/04/cancer-patients-try-experimental-meds-in-the-uk/#comment-294295 Former pharma Marketing Exec Fri, 18 Apr 2008 22:11:05 +0000 http://www.pharmalot.com/2008/04/cancer-patients-try-experimental-meds-in-the-uk/#comment-294295 All, As reported, cancer drugs are used on real patients in phase one in the US who have no other alternative. Nathan is right, it isn't for the good of the patient, but the patient may derive some benefit. However, the problem is that Phase one is dose escalation trial (in cancer) and the problem is that the patient might develop resistance before they derive a benefit at all. I am not sure why the patient mentioned was allowed to be in 4 trials somewhat simultaneously, not very good planning. But depending on the drugs studied there could be some delayed benefits that is causing the problem. Usually the time lapse between trials is about 6 weeks for a "washout" period. For the record, we should look at this as a potential solution to the problem we have here with regards to the issues of the Abigail Alliance as I posted on another thread http://www.abigail-alliance.org/ Thanks for both of these Ed. All,

As reported, cancer drugs are used on real patients in phase one in the US who have no other alternative. Nathan is right, it isn’t for the good of the patient, but the patient may derive some benefit. However, the problem is that Phase one is dose escalation trial (in cancer) and the problem is that the patient might develop resistance before they derive a benefit at all.

I am not sure why the patient mentioned was allowed to be in 4 trials somewhat simultaneously, not very good planning.

But depending on the drugs studied there could be some delayed benefits that is causing the problem. Usually the time lapse between trials is about 6 weeks for a “washout” period.

For the record, we should look at this as a potential solution to the problem we have here with regards to the issues of the Abigail Alliance as I posted on another thread http://www.abigail-alliance.org/

Thanks for both of these Ed.

]]> By: Nathan http://www.pharmalot.com/2008/04/cancer-patients-try-experimental-meds-in-the-uk/#comment-293000 Nathan Fri, 18 Apr 2008 17:16:41 +0000 http://www.pharmalot.com/2008/04/cancer-patients-try-experimental-meds-in-the-uk/#comment-293000 Dan, That makes since for the individual. However, experimental drugs are not on the open market yet. The FDA approves an IND for a particular investigation. Treatment of patients with the experimental drug is NOT for the good of the patient. The purpose of the treatment is to test a hypothesis and to establish the efficacy and safety of a potential new drug. Uses that don't fit into this role should not be allowed (in my opinion). Their only use should be for experimental treatment. If one cannot discern the results of experimental treatment (which one of these 5 drugs actually helped?), then the "experiment" was a failure. This is similar to the issue explored by the supreme court back in January. Link below: http://www.pharmalot.com/2008/01/us-supreme-court-no-review-of-experimental-meds/ Dan,
That makes since for the individual. However, experimental drugs are not on the open market yet. The FDA approves an IND for a particular investigation. Treatment of patients with the experimental drug is NOT for the good of the patient. The purpose of the treatment is to test a hypothesis and to establish the efficacy and safety of a potential new drug. Uses that don’t fit into this role should not be allowed (in my opinion).
Their only use should be for experimental treatment. If one cannot discern the results of experimental treatment (which one of these 5 drugs actually helped?), then the “experiment” was a failure. This is similar to the issue explored by the supreme court back in January. Link below:
http://www.pharmalot.com/2008/01/us-supreme-court-no-review-of-experimental-meds/

]]> By: Dan http://www.pharmalot.com/2008/04/cancer-patients-try-experimental-meds-in-the-uk/#comment-292666 Dan Fri, 18 Apr 2008 16:04:02 +0000 http://www.pharmalot.com/2008/04/cancer-patients-try-experimental-meds-in-the-uk/#comment-292666 From a logical paradigm, if a candidate for an experimental med is likely to die soon, should they not explore all possible methods of treatment? From a logical paradigm, if a candidate for an experimental med is likely to die soon, should they not explore all possible methods of treatment?

]]> By: RTW http://www.pharmalot.com/2008/04/cancer-patients-try-experimental-meds-in-the-uk/#comment-292567 RTW Fri, 18 Apr 2008 15:38:03 +0000 http://www.pharmalot.com/2008/04/cancer-patients-try-experimental-meds-in-the-uk/#comment-292567 Jack2. You are correct. In general most anti-cancer drugs are tested in phase I cancer patents usually expressing the type of cancer the drug is meant to treat, although sometimes they will admit other cancer patents in trials aimed at discovering synergies between drugs in combination for example. There has been a lot of talk in doing double blind studies and studies in healthy volunteers but the ethics of such a process are less than optimal when dealing with something that can be as toxic to normal tissue sometimes as cancerous tissues. This is changing as we better understand cell signaling and seek to use non toxic drugs to control or manage cancer more in lines with how diabetes is managed. Jack2. You are correct. In general most anti-cancer drugs are tested in phase I cancer patents usually expressing the type of cancer the drug is meant to treat, although sometimes they will admit other cancer patents in trials aimed at discovering synergies between drugs in combination for example.

There has been a lot of talk in doing double blind studies and studies in healthy volunteers but the ethics of such a process are less than optimal when dealing with something that can be as toxic to normal tissue sometimes as cancerous tissues. This is changing as we better understand cell signaling and seek to use non toxic drugs to control or manage cancer more in lines with how diabetes is managed.

]]> By: Jack2 http://www.pharmalot.com/2008/04/cancer-patients-try-experimental-meds-in-the-uk/#comment-292100 Jack2 Fri, 18 Apr 2008 12:20:39 +0000 http://www.pharmalot.com/2008/04/cancer-patients-try-experimental-meds-in-the-uk/#comment-292100 My understanding is that in the US, Phase 1 cancer studies are not done in healthy volunteers - because of the high toxicity risk of these drugs. In the US industry does not test them in healthy volunteers, ever, at any phase. I don't know why this study mentions healthy volunteers. Perhaps its a UK/US difference or an academia/industry difference. My understanding is that in the US, Phase 1 cancer studies are not done in healthy volunteers - because of the high toxicity risk of these drugs. In the US industry does not test them in healthy volunteers, ever, at any phase.

I don’t know why this study mentions healthy volunteers. Perhaps its a UK/US difference or an academia/industry difference.

]]> By: Ed Silverman http://www.pharmalot.com/2008/04/cancer-patients-try-experimental-meds-in-the-uk/#comment-291936 Ed Silverman Fri, 18 Apr 2008 11:23:05 +0000 http://www.pharmalot.com/2008/04/cancer-patients-try-experimental-meds-in-the-uk/#comment-291936 Hi Nathan, I linked to the AP story because I'm not in the UK to report this myself and it's an interesting development. Two, I'm not sure that you will find the answers to all your questions. I'm afraid the story doesn't say which specific phase of development. And so I understand your frustration, because that's a good question. Nonetheless, one point the story makes is a contrast between the UK and US systems. Access to experimental meds is an issue here. Regards ed Hi Nathan,

I linked to the AP story because I’m not in the UK to report this myself and it’s an interesting development. Two, I’m not sure that you will find the answers to all your questions. I’m afraid the story doesn’t say which specific phase of development. And so I understand your frustration, because that’s a good question. Nonetheless, one point the story makes is a contrast between the UK and US systems. Access to experimental meds is an issue here.

Regards
ed

]]> By: Nathan http://www.pharmalot.com/2008/04/cancer-patients-try-experimental-meds-in-the-uk/#comment-291915 Nathan Fri, 18 Apr 2008 11:15:42 +0000 http://www.pharmalot.com/2008/04/cancer-patients-try-experimental-meds-in-the-uk/#comment-291915 Ed, Maybe I should read the AP article -- but I'm a little confused. Are we talking about drugs in Phase I, Phase II, or Phase III? It seems as if they are talking about Phase I. If that's the case, I don't see a lot of point in this exercise because Phase I trials are usually conducted in healthy volunteers -- the dose is only escalated briefly to look for side effects, probably not long enough to see a therapeutic effect. Also, I'm confused by this statement: "Under government-supported trials, Cowley has tried at least four experimental meds for free. Her doctors aren’t sure which ones have had the most impact but say her situation is stable." Aren't these controlled clinical trials? Or is this just some doctors giving experimental medicines to patients who are not part of clinical trials? It's hard to imagine a drug company allowing enrollment in 4 cancer clinical trials. As the statement above points out, it would be nearly impossible to tell which drug had an effect. The experimental treatments may have helped this woman -- but they did no good for all the other cancer patients out there waiting for new treatments. The point of clinical trials is not to help the individual -- it's to see if the drug can help the larger population. In this woman's case, that didn't seem to happen. Ed,
Maybe I should read the AP article — but I’m a little confused. Are we talking about drugs in Phase I, Phase II, or Phase III? It seems as if they are talking about Phase I. If that’s the case, I don’t see a lot of point in this exercise because Phase I trials are usually conducted in healthy volunteers — the dose is only escalated briefly to look for side effects, probably not long enough to see a therapeutic effect.

Also, I’m confused by this statement: “Under government-supported trials, Cowley has tried at least four experimental meds for free. Her doctors aren’t sure which ones have had the most impact but say her situation is stable.” Aren’t these controlled clinical trials? Or is this just some doctors giving experimental medicines to patients who are not part of clinical trials? It’s hard to imagine a drug company allowing enrollment in 4 cancer clinical trials. As the statement above points out, it would be nearly impossible to tell which drug had an effect. The experimental treatments may have helped this woman — but they did no good for all the other cancer patients out there waiting for new treatments. The point of clinical trials is not to help the individual — it’s to see if the drug can help the larger population. In this woman’s case, that didn’t seem to happen.

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