May 16 2009 post. In one of my posts on feverfew/parthenolide (PTL)/DMAPT, I mentioned en passant a 2004 Phase I feverfew trial…but I recall that I only glanced at the abstract and, back then, didn’t have access to the full study. Then I must have forgotten about it. Well, it just so happened that last week Sherlock (sei fantastica!) found and sent me a bunch of full studies on various topics, including, yippee, the 2004 feverfew trial study (abstract: http://tinyurl.com/qd7l85). Super!
Oh, before discussing the full study, I just wanted to say two more things. 1. I have planted two more feverfew plants in my front yard. The one that I planted last year barely made it through the summer and then died, much to my sorrow. It was my own bloody fault. It was a hot summer so I kept watering it…and I probably ended up drowning the poor thing. This just goes to show that too much love and attention and may not necessarily be a good thing. Anyway, this year I will do my best not to over-water the two plants that Stefano’s aunt sent to us from southern Italy. Fingers crossed. Actually, thus far they are doing fine…indeed, they are about to flower; as soon as that happens, I will post some photos.
2. In November 2008, soon after taking my first feverfew pill (not the Tanacet brand used in the 2004 clinical trial, by the way, but another brand containing a slightly higher PTL percentage), I felt a surge of heat on my upper lip. I checked in the mirror, and there it was: a small but rather angry cold sore. Stefano accompanied me to a pharmacy to buy some zovirax cream that I dabbed on the spot. The following day it had vanished. Other than that minor incident, I didn’t have any particular problems with feverfew.
Okay, now for the study. The abstract, which you can go read on your own, explains what feverfew is, gives the basic info about the trial and so on. As many as 4 mg of feverfew were given to a small group of cancer patients who experienced no significant toxicity. Interestingly, the maximum tolerated dose was not reached. I had to read the entire study to find out why.
On the down side, even at the highest dose—4 mg—there was no detectable concentration in the plasma. That means that feverfew is probably poorly bioavailable, as the researchers also suggest further on in the study. But, because of my initial reaction to the feverfew pill (the cold sore, I mean), I wonder if, like curcumin, feverfew might work on different areas in the body…other than the bloodstream, that is. These are the ramblings of a non-scientific mind, of course. Okay, let’s take a look at the full study.
The first paragraph makes the point that many chemo drugs derive from plant extracts: The taxanes, paclitaxel and docetaxel, are very important anti-cancer drugs derived from the yew plant family. Then we read a list of parthenolide’s properties…the main ones are potent in vitro anticancer and antiangiogenic properties, inhibition of NF-kB, IL-6, IL-8 and drug resistance.
The purpose of this clinical trial was to see if PTL would show up in cancer patients’ blood. It was administered daily for 28 days. Subsequent 28-day cycles were administered with an intervening break. No more than 4 mg/day were given because of drug supply issues…and financial considerations. Aha, that explains why the maximum tolerated dose wasn’t reached in this trial.
The patients took feverfew capsules (brand: Tanacet) containing 500 mcg of PTL, in the morning on an empty stomach (ahhh, how I loved all these details!). They were instructed not to eat for 1 hour after ingestion. More details: In cycle 1, blood samples were drawn on day 1 and 29 in the following fashion: pretreatment, and then 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 12, and 24 hours after the ingestion of the capsules.
Patient information: Twelve patients with advanced solid tumors were treated with feverfew. The median age was 73 years (range 48 to 80). There were 11 men and 1 women enrolled. The cancers treated included eleven prostate and one breast and all patients had metastatic disease and had received prior therapy.
Problems. Even though the patients experienced no significant toxicities, the trial was stopped at the dose level of 4 mg daily once it was determined that no parthenolide was identified in the plasma of any of the patients. By the way, side effects included: fever, gastrointestinal side effects, chills, fatigue, and blurred vision. The blurred vision and fever were experienced by a diabetic patient, therefore causes other than the feverfew were considered more likely.
The ominous statement, “No patients responded to therapy,” certainly did not bode well for my own recent experiment with feverfew. You see, I took one 600 mcg PTL pill, that is, quite a bit less than the 4 mg/day dose…it seems that I should have been taking 5 or 6 pills. Well, live and learn. But the researchers had also written that, while some patients requested to leave the study and others left because of disease progression, some (no details given) had responding or stable disease, with no appearance of new lesions, and were thus allowed to stay in the study for six cycles. Furthermore, If a patient had evidence of continued response after 6 cycles, treatment was to be continued for two more cycles beyond the best response. Okay, there is no question that this part is more than a tad confusing. Perhaps I should write directly to the researchers. In any case, as far as my own experience is concerned, I have been taking feverfew since November 2008…so perhaps, uhm, the temporal effect added to my wishful thinking and positive attitude will make a difference. Realistically, though, I won’t be surprised if my next test results don’t change one whit.
Toward the end of the study, the researchers state that their efforts will now focus on purifying parthenolide and identifying causes for the inability to deliver systemic levels with low doses such as 4 mg of parthenolide per day. And, further on, The data from our trial supports the need to purify parthenolide and administer higher doses. I wish them success!