Yesterday's excerpts from Ralph Moss' paper on antioxidant use during chemo and radiation was a sort of baseline for the series of excerpts that I will post today and to come.

1) "In short, although they are sold over the counter, antioxidants are serious medicine. They  may have beneficial effects in ameliorating the notorious toxicity of radiation and  chemotherapy. But precisely because of their power, they may also have some negative  effects as well. Therefore, although the patient has a critical role to play in directing his  or her own care, the proper use of antioxidants, especially during conventional treatment,  requires the assistance and oversight of a knowledgeable integrative oncologist."

This comment is one that i consider the most important is this discussion- antioxidants are serious medicine.  The may have beneficial effects in protecting our bodies against side effects.  But antioxidants may also have negative effects as well.  I will try to outline both the plus' and minus' accordingly. 

The excerpt that I am citing today from Ralph Moss' study of antioxidant support during conventional therapy is one that so old and well documented that it's difficult to understand why my onc didn't mention it before I began V.A.D. therapy in '95. David

"Coenzyme Q10

Another area in which antioxidants may play a critical role is in preventing the toxicity of  the class of chemotherapy drugs known as the anthracyclines, in particular doxorubicin  (Adriamycin). This class of drugs has a major health-impairing as well as dose-limiting  effect: it can lead to irreversible damage to the heart muscle. This phenomenon was  described more than three decades ago (Lefrak 1973, Alexander 1979). Even today,  despite widespread acknowledgement of this effect, some patients are still suffering and  even dying of congestive heart failure (CHF), caused by anthracycline use (Magne 2005). 

Yet, oddly, Dr. D’Andrea fails to discuss either the problem or its potential solution. (She  provides one footnote that references the use of vitamin E in this context.) The mechanism by which anthracyclines damage the heart is well understood.  Yet, according to Prof. Conklin, and many others, anthracycline-induced cardiotoxicity is  easily preventable. Both preclinical and clinical studies suggest that the antioxidant  coenzyme Q10 (Co Q10) administered before, during, and after anthracycline  chemotherapy can largely prevent the heart damage for which that drug is notorious  (Conklin 2005)." 

A post in today's acor listserv discusses supplementation to prevent or reduce peripheral neuropathy- acetyl-l-carnatine- First I will excerpt the Moss study on the same subject then cut and paste the article-

1) "The platinum-based drug cisplatin causes neurotoxicity (nerve damage) in 15 to  20 percent of patients (Fossa 2004). Certain nutrients may offer a protective  effect. A randomized controlled trial (RCT) was conducted to measure the  neuroprotective effect of vitamin E in patients who were being treated with  platinum-based chemotherapy (cisplatin). Forty-seven patients were randomly  assigned to either receive vitamin E supplementation during cisplatin  chemotherapy, or to receive cisplatin chemotherapy alone. A dose of 300 mg per  day of vitamin E (alpha-tocopherol) was administered orally before cisplatin  chemotherapy, and daily administration of vitamin E continued for 3 months after  the end of that treatment. The incidence and severity of nerve damage was  significantly lower in the vitamin E-treated group (30.7 percent) than in the  cisplatin group (85.7 percent). The authors concluded, “Supplementation of  patients receiving cisplatin chemotherapy with vitamin E decreases the incidence  and severity of peripheral neurotoxicity,” (i.e., nerve damage to the extremities).  Furthermore, in the clinical work, as well as in preclinical studies, no interference  was seen between vitamin E and cisplatin (Pace 2003).

2) "Acetyl-L-Carnitine for the Treatment of Chemotherapy-Induced Peripheral Neuropathy-Peripheral neurotoxicity is a major complication
associated with the use of chemotherapeutic agents such as platinum compounds, taxanes and vinca alkaloids.
The neurotoxicity of chemotherapy depends not only on
the anticancer agent(s) used, the cumulative dose and the delivery
method, but also on the capacity of the nerve to cope with the nerve-damaging process. The sensory and
motor symptoms and signs of neurotoxicity are disabling,
and have a significant
impact on the quality of life of cancer patients.
Moreover, the risk of cumulative
toxicity may limit the use of highly effective
chemotherapeutic agents. Therefore,
prophylaxis and treatment of peripheral neurotoxicity
secondary to chemotherapy
are major clinical issues.
Acetyl-L-carnitine (ALC), the acetyl ester of
L-carnitine, plays an essential
role in intermediary metabolism. Some of the properties
exhibited by ALC
include neuroprotective and neurotrophic actions,
antioxidant activity, positive
actions on mitochondrial metabolism, and stabilisation
of intracellular membranes.
ALC has demonstrated efficacy and high tolerability in
the treatment of
neuropathies of various aetiologies, including
chemotherapy-induced peripheral
neuropathy (CIPN). In several experimental settings, the
prophylactic administration
of ALC prevented the occurrence of peripheral
neurotoxicity commonly
induced by chemotherapeutic agents. In animal models of
CIPN, ALC administration
promoted the recovery of nerve conduction velocity,
restored the mechanical
nociceptive threshold, and induced analgesia by
up-regulating the expression of
type-2 metabotropic glutamate receptors in dorsal root
ganglia. These results, plus
the favourable safety profile of ALC in neuropathies of
other aetiologies, have led
to the effects of ALC on CIPN being investigated in
cancer patients. Preliminary
results have confirmed the reasonably good tolerability
profile and the efficacy of
ALC on CIPN. The present studies support the use of ALC
in cancer patients with
persisting neurotoxicity induced by paclitaxel or
cisplatin treatment.

Ralph Moss cites vitamin E supplementation for two specific benefits-

1) " Another RCT (ransomized controlled trial) on the use of vitamin E for the prevention of chemotherapy-induced neuropathy found that such nerve damage occurred in 73.3 percent of those who received chemotherapy alone vs. just 25 percent of those who also received vitamin E—a three-fold reduction in incidence (Argyriou 2005)."

I underwent local radiation in '96 to zap a plasmacytoma in my sacrum (tail bone). The radiation worked but I experience pain whenever I sit now. Did the radiation cause the bone death that Ralph refers to below? Could supplementation have reduced or prevented this side effect?

2)"From the same research group, there was more recently a clinical trial of pentoxifylline, vitamin E and clodronate to treat osteoradionecrosis (ORN), which is bone death that occurs as an adverse effect of radiation. This study also found that this three-agent regimen, including vitamin E, “is an effective treatment of mandibular ORN,” which “induces mucosal and bone healing in a median period of six months” (Delanian 2005)."

I have to share some bad news which in a way is good news for the rest of you because hopefully those of you on Revlimid or starting Revlimid will be alerted.  I have been on Revlimid for the past 10 months.  My dose was started at 10 mg and then went to 15 mg which was the highest dose I could tolerate without my WBC going too low.  My WBC would be 3.5 mg/dL at the start of the 21 day Revlimid cycle and then over the next 21 days drop to 1.5 mg/dL.  I would stay off the Revlimid for the next seven days (standard protocol) at which time my WBC would return to 3.5 mg/dL. 

Approximately 6 weeks ago, I noticed by WBC was 1.0 mg/dL at the end of the 21 day Revlimid cycle.  My Oncologist was not worried; however, I decided to recheck my WBC several days later.  To my surprise, my WBC had not increased from the 1.0 mg/dL.  (My neutraphils were only 580 mg/dL- I was very close to neutrapenia!)  I am also on 20 mg dexamethasone/wk and I spoke to my Oncologist and decided to discontinue the Revlimid until my WBC increased and just take the dexamethasone.  The Dex did increase my WBC to 2.1 mg/dL; however, 7 days later it was back to 1.2 mg/dL again.  My WBC cycle has not changed for the past 5 weeks.  This leaves me in a very bad spot because until the toxicity subsides, I am unable to treat my myeloma with any of the cytotixic drugs like Revlimid, thalidomide, or Velcade.  I have since learned that I am not the only patient with bone marrow toxicity from Revlimid.  A second autologus transplant may be in my future if my bone marrow does not recover on its own.

I am not recommending nor taking Revlimid.  I am saying, we need to be aware of potential side effects of these drugs even the side effects that aren't published yet.  I don't know what could have been done to avoid this toxicity or what I would have done differently.  I will try to keep you up to date as my condition changes.

Terry

Terry and all-

When I read

"I sort of feel like I was some what betrayed by the medical community and Celgene.  I believe the information on the clots and the bone marrow toxicity was out there before I came under attack.  I would have liked to been made aware so I could have changed my treatment such as starting the cumadin before the clots occurred..."

I cannot help but post my own blood clot experience.  As I have posted before, I have a chronic blood clot.  It first formed when I began VAD back in 4/95.  Long story short, I was put on coumadin and after about 1-1/2 years, I stopped this therapy and have managed my clot with general enzymes, nattokinase, fish oil, vit e and gingko- my clot is still there but much, much less of an issue for me.  I barely notice it now.

David 

Terry I'm so sorry you are going through this. But thank you for sharing your experience here.

Like David, I think your statement about feeling betrayed by the medical community is so true, sadly. I also (as you know from my rants!) feel betrayed by our doc, who has just not given us the kind of information that we have needed. For instance, if we'd left it up to him, my husband would still not have harvested stem cells - a year after diagnosis. The doc never tested Beta2 microglobulin at diagnosis, so that is one important prognostic marker that we just don't have. (If we had considered going to Arkansas, for instance, we would have needed that info to make the best possible decisions). At diagnosis we didn't know enough about anything, and we sure didn't get the information we needed to make the best decisions. What information we got was hard won, and it's taken a year to feel like we really understand more about what we are doing.

Sadly, I think it serves patients poorly to depend solely on their docs. Many docs are wonderful, but at the end of the day I guess it is up to us to get the information we need - and how are patients supposed to do that  when they are ill and scared and overwhelmed?

The more we post about our experiences, the more others will be able to remove their blinders, at least partially. So, every bad experience potentially helps others. It's just a shame that some people suffer so much as a result of the medical establishment. Suffering from the disease is really quite enough!

Hang in there,

Lisa 

Terry, good that your MM is still under control. But  so sorry about the other news. I guess all these drugs really are toxic - which we already know. But I hadn't realized the novel agents are also associated with other cancers - I thought it was the chemo drugs used in transplant which caused those problems.

The very best of luck, and keep us posted.

Lisa