AZT AND CANCER
By John Lauritsen
New York Native 30 Oct. 1989
It is urgently necessary to review the toxicity of AZT in
light of recent marketing developments. Prior to last August, AZT
therapy was officially indicated only for "AIDS" or "ARC" patients
who either had "a history of cytologically confirmed Pneumocystis
carinii pneumonia (PCP) or an absolute CD4 (T4 helper/inducer)
lymphocyte count of less than 200/mm3 in the peripheral blood
before therapy is begun." (Physician's Desk Reference) This
changed dramatically in August, when a series of press releases
were issued by the National Institute of Allergy and Infectious
Diseases (NIAID) and other branches of the Public Health Service
(PHS), claiming that AZT was beneficial for "HIV-infected" persons
with "mild symptoms of immune system damage" and also for "HIV-
infected persons who have not yet developed symptoms."
The old rationale for prescribing AZT was that people with
AIDS (PWAs) were suffering from a disease that was invariably
fatal, that such persons had only a few months to live, and that
AZT might extend their lives for a few more months. The idea was
that in a desperate situation, drastic measures were called for.
I have repeatedly argued that this viewpoint is wrong -- that
"AIDS" is not invariably fatal; that some PWAs have survived for
many years and appear to be recovering; and that the only chance
for recovery lies in strengthening the body, rather than injuring
it through toxic chemotherapy like AZT.
Now a completely different game plan is in operation. With
well-orchestrated propaganda emanating from NIAID, Gay Men's
Health Crisis (GMHC), Project Inform, and various and sundry other
"AIDS" groups, clinical researchers, and other confederates of
Burroughs Wellcome (the manufacturer of AZT), physicians are now
being urged to prescribe AZT for perfectly healthy people. The
targeted individuals -- estimated to be several hundreds of
thousands in the United States alone -- merely have antibodies to
HIV-1, a retrovirus that has not yet been proven to be harmful,
let alone the cause of the devastating AID Syndrome. Healthy
people, who ought to look forward to living for several more
decades, are now being conned into taking the most toxic substance
ever prescribed for long-term use. Since gay men are the primary
targets of AZT marketing, since AZT therapy would probably cause
even an athlete in his prime to die within a few years, and since
the alleged "benefits" of AZT rest upon fraud, it is not
unreasonable to use the word "genocide" to describe what is
happening.
The Great AZT Scam: Results Without Data
In my articles in the Native I have analyzed the studies
that allegedly demonstrate AZT's effectiveness, and have concluded
that there is no scientifically credible evidence that AZT has
benefits of any kind. Documents that the Food and Drug
Administration (FDA) was forced to release under the Freedom of
Information Act revealed that the Phase II ("double-blind,
placebo-controlled") AZT trials were worthless. The researchers
covered up the fact that the study had become unblinded (thus
violating the basic test design). Protocol violations were
overlooked. Worst of all, the researchers deliberately used data
that they knew were false. These fraudulent trials were the basis
of government approval of the drug. [note 1]
Another study often cited as proof of AZT's benefits
concerns patients who received AZT after the Phase II trials were
prematurely terminated. [note 2] I have written an extensive
analysis of this study, which is a rotten mixture of incompetence
and dishonesty. [note 3] Through colossal incompetence the
researchers lost track of 1120 patients, not knowing if they were
even alive or dead. They then used statistical projection methods
to guess what results they would have obtained if they had not
lost the 1120 patients, presented their guesses as actual survival
statistics, and made a number of grossly invalid comparisons in
order to claim that AZT had extended lives. This "research" is a
blatant exercise in disinformation, proving nothing except how
farcical are the "peer review" standards of medical journals.
As appalling as these two studies were, they at least
presented data, however dubious. The two studies that received so
much fanfare last August didn't even go that far. The general
public, physicians, PWAs, and health care workers were expected to
accept "findings" which consisted of generalizations that were not
even backed up by numbers. Normally a press release on a study is
issued a few days before the publication of a report in a peer-
reviewed medical journal. This is ethically obligatory, because
physicians with the responsibility of prescribing a drug --
especially one as toxic as AZT -- are entitled to have recourse to
hard data, a proper description of methodology, and an intelligent
analysis of the findings.
On 17 August 1989 The U.S. Department of Health and Human
Services (HHS) issued a press release, which began:
"A multicenter AIDS drug trial with more than 3,200
volunteers has shown that zidovudine (AZT) delays
progression of disease in certain HIV-infected persons who
have not yet developed symptoms."
The alleged findings of the study (known as ACTG Protocol
019) were described in a vague paragraph, which did not give a
single hard statistic. (See Box A following this article.)
Then on 24 August 1989 NIAID issued its own press release,
"Results of Controlled Clinical Trials of Zidovudine in Early HIV
Infection". This two-pager covered both Protocol 019 (healthy
persons) and Protocol 016 (persons with "mild symptoms"), and gave
even less information than the HHS statement had. It made the
preposterous assertion that "zidovudine toxicity experienced by
the persons studied in Protocol 019 was minimal."
I spent several days calling NIAID and various other PHS
branches in an attempt to obtain some hard information about
Protocol 019. They sent me a three-page "Backgrounder" entitled,
"ACTG 019 - Questions and Answers". This Q & A described the
"results" of the study in one paragraph. (See Box B following
this article.) As the reader can see, the statement in Box B is
gibberish, it gives no real data, and it is in contradiction with
the earlier HHS press release (Box A).
When I talked to the NIAID press officer who was supposed to
be most knowledgeable about Protocol 019, and asked him some
specific questions (which he was unable to answer), he told me
frankly that I had all of the information he himself had -- that
there was nothing he could tell me I didn't already know.
Based on my knowledge of Protocol 019, equal apparently to
that of anyone in the country, I constructed Table 1, which shows
the findings in the simplest and most straightforward way
possible. This table should be studied carefully by anyone
(whether as patient, physician, or concerned party) who is
considering the use of AZT for an "asymptomatic HIV-infected
person". Table 1 contains all of the data we have about Protocol
019. [Table 1 is found at the end of this article, following the
"Notes".]
Drug Regulation American Style
The ordinary mind often fails to make the distinction
between things as they are and things as they ought to be. For
example, if the FDA is to do its job and protect the American
public from dangerous drugs, it ought to have a system for keeping
track of adverse reactions to a drug after it has been put on the
market. Many people therefore assume that there is such a system.
There is not. In this regard the United States takes an approach
to drug regulation that is different from that of most other
industrialized countries.
In the United States, all of the efforts in screening a new
drug for adverse side effects are supposed to take place before
the drug is approved. Once a drug has been approved -- whether by
hook, crook, or the intrinsic merits of the product -- it's clear
sailing from then on. In theory, physicians are supposed to
report adverse effects to manufacturers, who are supposed to relay
the information to the FDA. But in practice, with no incentives
for compliance, no punishments for noncompliance, and with no
federal data gathering system, the post-marketing surveillance is
haphazard at best.
In contrast, Britain has a sophisticated and rigorously
enforced system of post-marketing surveillance. The philosophy
there is that some adverse effects of a drug only become apparent
after a certain period of time -- this is known as chronic
toxicity -- and that some adverse effects might be relatively
rare, found perhaps in only 1 in 1000, or 1 in 5000 persons.
Neither the chronic toxicity nor the rare adverse effects would
likely be identified in pre-marketing trials, which typically
involve only a few hundred subjects treated for a relatively short
time.
Most new drugs take 9 to 10 years to go through the FDA's
approval process, which includes initial safety tests in animals
and human beings, clinical trials for efficacy and safety, and
extensive review and analysis of the data. AZT, however, was
rushed through the approval process faster than any drug in the
FDA's history -- less than two years. As a result, the officially
recognized toxicities of AZT are far from complete. Further, the
"non-official" toxicities of AZT, well known through the
formidable PWA grapevine, are not being systematically recorded.
On top of all these problems, AZT was approved on the basis
of research that was not just inadequate, but fraudulent. It is
important to realize that the FDA has been for many decades a
notoriously corrupt agency. Time and again officials in the FDA
have colluded with drug manufacturers in order to suppress
information about a drug's side effects. Recently Dr. Sidney M.
Wolfe, director of the non-profit Public Citizen Health Research
Group (HRG), charged that under Commissioner Frank E. Young, the
FDA "is implicitly inviting all of the industries it regulates to
join in the lawlessness." [note 4] I am preparing a future
article that will review some of the well-documented crimes
against public health that have been committed through collusion
of drug manufacturers, the FDA and other branches of the PHS,
clinical researchers, and the American Medical Association.
The Chernov Review of AZT's Pharmacology & Toxicity
Among the documents which the FDA was forced to release
under the Freedom of Information ACT was the "Review & Evaluation
of Pharmacology & Toxicology Data" for the drug Retrovir (generic
name: zidovudine, aka AZT or azidothymidine), written by FDA
toxicology analyst Harvey I. Chernov, Ph.D., and submitted in its
final form on 29 December 1986. [note 5]
Chernov reviewed several dozen studies that had been
completed, including in vitro studies and experiments on rats,
mice, rabbits, beagle dogs, and human beings. Many additional
studies had not been completed or had been planned but not begun.
The single most important finding was that AZT was toxic to the
bone marrow, causing anemia. Chernov wrote:
"Thus, although the dose varied, anemia was noted in all
species (including man) in which the drug has been tested."
Chernov noted that AZT "was found weakly mutagenic in
vitro in the mouse lymphoma cell system. Dose-related chromosome
damage was observed in an in vitro cytogenetic assay using human
lymphocytes."
Evidence from the "Cell Transformation Assay" indicated that
AZT was likely to cause cancer. In Chernov's summary:
"This BALB/c-3T3 neoplastic transformation assay was
performed according to standard operating procedure.
Concentrations of AZT as low as 0.1 mcg/ml reduced the
number of cells in culture after a 3-day exposure. A
statistically significant increase in the number of aberrant
'foci' was noted at a concentration of 0.5 mcg/ml. This
behavior is characteristic of tumor cells and suggests that
AZT may be a potential carcinogen. It appears to be at
least as active as the positive control material,
methylcholanthrene [a known and extremely potent
carcinogen]."
Chernov was concerned that in the rush to approve AZT, the
FDA was violating its own guidelines and proceeding on the basis
of inadequate information:
"FDA guidelines would have prescribed more extensive
preclinical testing than that reported thus far. However,
the urgency for developing an anti-AIDS drug has been so
great that clinical testing has preceded the usual/customary
preclinical testing. For example, while data from a 6-month
clinical study are available, results of the supporting 6-
month preclinical toxicity studies have not yet been
submitted. Also, the applicant has a protocol for a 104-
week clinical study, whereas chronic (52-week preclinical
toxicity studies are not scheduled to start before January-
February of this year."
Taking into account all of the information available to him,
Chernov recommended that AZT should not be approved for
marketing:
"In conclusion, the full preclinical toxicological profile
is far from complete with 6-month data available, but not
yet submitted, one-year studies to begin shortly, etc. The
available data are insufficient to support FDA approval."
AZT and Cancer
Obviously if AZT is going to be prescribed to healthy (if
"HIV-infected") people, with the expectation that they will take
the drug for the rest of their lives, it is important and
ethically imperative that physicians and patients be fully
informed on the issue of carcinogenicity. But Burroughs Wellcome
and their accomplices in the FDA have done their best to sweep
carcinogenicity under the rug. Back in 1986 Burroughs Wellcome
proposed dealing with the results of the Cell Transformation Assay
by saying on the Retrovir label, "The significance of these in
vitro results is not known."
This proposed labelling was criticized by the FDA toxicology
analyst, Harvey Chernov, for being misleading:
"The sentence: 'The significance of these in vitro results
is not known.' is not accurate. A test chemical which
induces a positive response in the cell transformation assay
is presumed to be a potential carcinogen." [note 6]
Burroughs Wellcome resolved this problem by simply dropping
the offending sentence, with the end result being every bit as
obscurantist. In the Retrovir entry in Physicians' Desk
Reference, written by Burroughs Wellcome, carcinogenicity is
dealt with in the following way:
"Long-term carcinogenicity studies of zidovudine in animals
have not been completed. However, in an in vitro
mammalian cell transformation assay, zidovudine was positive
at concentrations of 0.5 mcg/ml and higher."
Well now, how many physicians would know what these findings
meant? Damned few, if any. Chernov said what the findings meant:
AZT is presumed to be a carcinogen! But most physicians would
assume that AZT was not carcinogenic, for the simple reason that
the Physicians' Desk Reference entry hadn't said it was.
In toxicology a basic distinction is made between acute
toxicity and chronic toxicity. Acute toxicity refers to those
adverse effects that are manifest within a relatively short period
of time (if not necessarily immediately). Chronic toxicity refers
to adverse effects that only become apparent over time. It is a
truism of toxicology that chronic toxicity cannot be predicted
from acute toxicity.
There are several kinds of chronic toxicity. In one kind, a
single exposure to the substance can result in illness many years
later -- this appears to be the case with Agent Orange (dioxin).
Another kind of chronic toxicity involves an accumulation of the
substance within the body, after which symptoms occur. Still
another kind of chronic toxicity, involves the accumulation of
injury:
"Consider the circumstances of a small degree of
irreversible injury resulting from each of a series of
doses. If the change effected by a single divided dose is
truly irreversible, the end result of a series of doses may
be essentially identical with the effect of the same total
dose given at one time." [note 7]
It takes time to determine the potential of a substance to
cause cancer. This is one reason why Chernov objected to the
approval of AZT before the completion of long-term carcinogenicity
studies. In the words of a toxicology expert:
"Time as well as dose is a factor in assessing properties of
chemical carcinogens as compared to drugs. It is in this
way that carcinogens differ from ordinary toxic agents. A
number of small doses give no overt signal of their presence
and in due time can yield tumors within the life-span of a
host. With noncarcinogens such low dosages would be
completely innocuous." [note 8]
The point regarding "low dosages" is especially relevant in
the case of AZT. Many PWAs have been led to believe that if they
are on low dosages of AZT, they will evade the terrible toxicities
of the drug. Perhaps they will to some extent evade the acute
toxicities, but only time will tell what chronic toxicities lie
in wait, including cancer.
Samuel Broder of the National Cancer Institute (NCI) is the
man who is more responsible than anyone else for the development
and promotion of AZT. (For this role, molecular biologist Peter
Duesberg has nominated Broder for the annual Dr. Josef Mengele
award.) Even Broder now admits that his drug may cause cancer.
He is co-author of a recently published article in the New
England Journal of Medicine (NEJM), in which it is stated:
"In considering early intervention with zidovudine, it is of
particular concern that the drug may be carcinogenic or
mutagenic; its long-term effects are unknown." [note 9]
Having made this admission, the authors engage in some
strangely sophistical reasoning: "Zidovudine may be associated
with a higher incidence of cancers in patients whose
immunosurveillance mechanisms are disturbed, simply because it
increases their longevity." Of course, other things being equal,
increased longevity increases one's risk for all kinds of things,
including perishing in an earthquake, dying of old age, or having
dinner with an anti-porn feminist. However, Broder & Company are
wrong to assert that AZT increases longevity, for "patients whose
immunosurveillance mechanisms are disturbed". I challenge them,
or anyone else, to cite a single, scientifically credible study,
that proves this.
Muscular Atrophy and Other Unofficial AZT Side Effects
As mentioned above, there is no official, on-going
surveillance of AZT's side effects. Nevertheless, we have a
pretty good idea what some of them are from the PWA grapevine.
And occasionally some unofficial side effects surface in letters
to medical journals or in off-the-cuff comments at AIDS
conferences. One such side effect is muscular atrophy coupled
with intense muscular pain. Many PWAs have experienced this
condition. For example, Peabody in San Francisco wrote:
"After being on a full dose of AZT for about 10 months, I
started to go downhill -- more fatigue, headaches,
nausea/dizzy feeling, painful intestinal cramping AND loss
of mass in my legs. I'm not sure if this loss of mass is
muscle or fat. I lost about 8 lbs and was having sciatic
like leg pains. I went off the AZT completely and now I
feel almost normal. Much more energy, less of the other
symptoms. BUT I'm worried about my skinny legs and bony
butt. My doctor thinks it's HIV related -- but what do
doctors know! I had the leg pain and loss of mass while on
the AZT and feel better off the AZT." [note 10]
Another PWA, Diogenes, wrote:
"I had the same experience on AZT with leg pain and muscle
loss. Been off AZT 2 mos. now and pains are almost
completely gone -- also muscle soreness and loss of muscle
tone has reversed somewhat." [note 11]
Instances of severe muscular atrophy and pain caused by AZT
were reported in a letter to the New England Journal of
Medicine. The physicians observed:
"All patients had an insidious onset of myalgias, muscle
tenderness, weakness, and severe muscle atrophy favoring the
proximal muscle groups. Physical examinations revealed
varying degrees of muscle weakness and grossly apparent
atrophy. Weight loss due to muscle loss was uniformly
noted; in one patient, the loss was a striking 18 kg. [40
pounds]."
The physicians held AZT responsible for the muscular atrophy
and pain:
"We did not observe this illness before zidovudine was
available, the disorder was seen in patients taking the drug
for extended periods, and the syndrome was ameliorated after
the drug was stopped." [note 12]
A leading British AIDS doctor, Dr. Matthew Helbert, sent
Burroughs Wellcome stock into a temporary tailspin when be
publicly commented on muscular atrophy and other serious, but not
officially acknowledged, side effects of AZT:
"Biting hard on the hand that had paid his air fare, he
placed heavy emphasis on new, debilitating and sometimes
deadly side-effects of Retrovir on some of his Aids
patients. Some men's muscles had degenerated dramatically
after long-term use of the drug. Others had rapidly
developed a serious brain disease, encephalitis, soon after
being taken off the drug. Given the company's duty to keep
a new drug under active surveillance, Dr. Helbert asked why
the company had not picked up similar cases among the
thousands of people treated with Retrovir for a year or more
in the United States." [note 13]
Other well-known, but not officially acknowledged, side
effects of AZT include damage to the kidneys, liver, and nerves.
An old friend of mine was one of the earlier patients to be put on
AZT. Everyone thought he was doing well. For almost a year he
was occasionally able to work or go to concerts. Then one day he
went into complete paralysis, and he died two days later. Now,
paralysis is not an officially recognized side effect of AZT;
there is no warning about it on the package. Nevertheless, there
is a connection.
Peter Duesberg has repeatedly referred to AZT as a "poison",
and with good reason. AZT is cytotoxic -- it kills cells. AZT
terminates DNA synthesis, the very life process itself, by which
new cells are formed and grow. It is in the very nature of AZT to
kill healthy cells. Therefore, damage to the muscles, to the
nerves, and to each and every organ of the body should be
considered expected consequences of AZT therapy.
Ethics
I believe that history will severely condemn the ethical
shortcomings of such AZT promoters as Samuel Broder, Anthony
Fauci, and Margaret Fischl. In their zeal to expand the market
for AZT, they have unconscionably failed to inform the public
about the likely long-term consequences of AZT therapy.
I also believe that history will condemn the physicians,
"AIDS groups" and individuals who have been urging healthy ("HIV-
infected") gay men to take AZT.
Two years ago I wrote in the Native that "It is
malpractice for physicians to prescribe AZT, a poison which can
only harm the patient." [note 14] I reaffirm this judgment. When
physicians coax and cajole and bully their "HIV-positive" patients
into taking AZT, do they tell them that the long-term effects of
AZT are unknown?...that AZT is cytotoxic?...that AZT destroys bone
marrow?...that AZT causes muscular atrophy and pain?...that AZT
terminates DNA synthesis?...that AZT damages the nerves, kidneys,
and liver? Do they tell their patients that AZT will probably
cause cancer in the long run? If not, these physicians have
failed to inform their patients about the dangers of a drug whose
"benefits" have yet to be demonstrated.
And I issue this challenge to the AZT doctors. If you know
of a single scientifically credible study -- just one -- which
proves that AZT is beneficial -- for PWAs, for people with ARC,
for healthy ("HIV-infected") people, or for anyone else -- then
let me know. I would certainly acknowledge it publicly.
Dr. Joseph Sonnabend has said that "AZT is incompatible with
life." In a recent conversation Sonnabend said that Fauci,
Fischl, and the other AZT advocates have been remiss, and indeed
criminally negligent, in not mentioning the likelihood that long-
term use of AZT may result in cancer. I believe that ten years
from now, looking back over tens of thousands of horrible, AZT-
related deaths, no reasonable person will disagree with his
verdict.
Notes
1. John Lauritsen, "AZT on Trial: Did the FDA Rush to Judgment --
And Thereby Further Endanger the Lives of Thousands of People?",
New York Native, Issue 235, 19 October 1987.
Another highly critical review of the Phase II trials was
written by Joseph A. Sonnabend, "Review of AZT Multicenter Trial
Data Obtained Under the Freedom of Information Act by Project
Inform and ActUp", privately published, New York City, 1987.
2. Terri Creagh-Kirk et al., "Survival Experience Among Patients
With AIDS Receiving Zidovudine [AZT]: Follow-up of Patients in a
Compassionate Plea Program", Journal of the American Medical
Association, 25 November 1988.
3. John Lauritsen, "On The AZT Front: Part Two", New York
Native, 16 January 1989.
4. Morton Mintz, "Anatomy of a Tragedy", New York Newsday, 3
October 1989.
5. Harvey I. Chernov, Ph.D., Review & Evaluation of Pharmacology
& Toxicology Data, NDA 19-655, 29 December 1986. (FDA document
obtained under the Freedom Of Information Act).
6. Harvey Chernov, op. cit..
7. Louis J. Casarett, "Toxicologic Evaluation", a chapter in
Toxicology: The Basic Science of Poisons, edited by Louis J.
Casarett, Ph.D., and John Doull, M.D., Ph.D., New York, Toronto,
and London, 1975.
8. John H. Weisburger, "Chemical Carcinogenesis", a chapter in
Casarett and Doull, op. cit..
9. Robert Varchoan, Hiroaki Mitsuya, Charles E. Myers, and Samuel
Broder, "Clinical Pharmacology of 3'-Azido-2'3'-Dideoxythymidine
(Zidovudine) and Related Dideoxynucleosides", New England Journal
of Medicine, 14 September 1989.
10. Communication from Peabody, Public Forum, AIDS Information
Bulletin, San Francisco: (415) 626-1246 [1200 baud] or (415) 626-
3518 [2400 baud].
11. Communication from Diogenes, ibid..
12. Laura J. Bessen et al., "Severe Polymyositis-Like Syndrome
Associated With Zidovudine Therapy of AIDS and ARC" (letter), New
England Journal of Medicine, 17 March 1988.
13. Duncan Campbell, "The Amazing Aids Scam", The New Statesman,
24 June 1988.
14. John Lauritsen, "AZT on Trial...".
Box A
"The Board found that, in those participants with fewer than 500
T4 cells who received zidovudine [AZT], the rate of progression to
AIDS or severe ARC was roughly half that for participants with
fewer than 500 T4 cells who received placebo. Progression to
symptoms was about the same in patients receiving either 500 mg
per day of 1,500 mg per day of the drug. Toxicities were minimal
in both treatment groups. More importantly, with the exception of
nausea that occurred in about 3 percent of the volunteers,
virtually no differences in side effects were observed in persons
receiving the lower dose and persons receiving placebo."
(From press release, U.S. Department of Health and Human Services,
17 August 1989)
Box B
What were the actual results?
"Zidovudine [AZT] delayed the onset of advanced ARC or AIDS for
individuals who entered the study with less than 500 T4 cell
counts. As of August 10, 1989, 38 individuals randomized to
placebo had developed endpoints (33 of which were AIDS). Only 17
individuals randomized to 100 mg zidovudine five times daily had
developed endpoints (11 of which were AIDS), and 19 individuals
receiving 300 mg five times daily developed endpoints (14 of which
were AIDS). The substantial difference in outcome between
treatment groups was observed for those entering the study with a
T4 cell count less than 500. However, for individuals entering
with T4 cell counts between 500 and 800, fewer endpoints occurred,
and no definite statement regarding differences in event rates can
be made at this time."
(From /Backgrounder: ACTG 019 - Questions and Answers, National
Institute of Allergy and Infectious Diseases, 17 August 1989)
Table 1
"Results" From NIAID-Conducted Protocol 019
Placebo-Controlled Trial In Asymptomatic HIV-Infected Persons
Total ________Treatment_______
Sample* AZT Placebo
Bases: ( ? ) ( ? ) ( ? )
# % # % # %
Progressed to "AIDS"
or "Advanced ARC"** ? ? ? ? ? ?
Duration of Treatment:
Range (months) (?) (?) (?)
Mean (months) (?) (?) (?)
Median (months) (?) (?) (?)
*According to NIAID, "more than 3200 asymptomatic HIV-infected
volunteers" were enrolled "approximately two years ago". However,
all studies have drop-outs. NIAID does not state how many
volunteers were still participating when the study was terminated.
**Also sometimes referred to as "severe ARC"; neither term has
ever been defined.