Institute Studies of Hydrazine Sulfate
In the 1980s and 1990s,
the National Cancer Institute (NCI) sponsored studies of hydrazine sulfate
in order to evaluate whether the compound might improve patient survival or
help reverse cancer cachexia, a wasting syndrome that occurs in almost all
terminal cancer patients. This syndrome profoundly affects the patients’
quality of life as well as their health, causing weight loss, fatigue,
weakness, and a loss of appetite (anorexia).
After hydrazine sulfate
showed promising results in a small pilot study, three large-scale,
randomized studies of the compound were undertaken in patients with advanced
cancers. Clinical trials are carried out to determine, in an objective,
unbiased way, whether new treatments are safe and effective in people. These
three clinical trials, published in June 1994, showed no benefit from
hydrazine sulfate in patient survival, weight loss, or quality of life.
Supporters of hydrazine
sulfate claimed that the studies were compromised because patients were
permitted to take tranquilizers, alcohol, and barbiturates, compounds they
said interfered with hydrazine sulfate, based on animal and laboratory
studies. NCI scientists had reviewed the same data and disagreed on the need
to prohibit those drugs, which were permitted in two of the three large
studies. At the request of Congress, an investigation of the allegations was
undertaken by the Government Accounting Office (GAO) beginning in July 1994
and lasting until April 1995.
After intense scrutiny,
the GAO found that while tranquilizers, alcohol, and barbiturates were
permitted in the studies, "subsequent analyses of the use of concurrent
medications found no evidence to invalidate NCI’s conclusion that
hydrazine sulfate is ineffective."
NCI stands behind the
findings of the 1995 GAO report, "Cancer Drug Research: Contrary to
Allegation, the National Institutes of Health Hydrazine Sulfate Studies Were
Not Flawed." Because studies of hydrazine sulfate in more the 600
cancer patients showed no benefit in terms of patient survival, weight loss,
or quality of life, no new NCI studies are planned.
Although the Food and
Drug Administration (FDA) has not approved hydrazine sulfate for marketing
in the United States, a number of drugs that help fight cancer cachexia have
been approved by the FDA and are available to cancer patients. NCI supports
hundreds of clinical studies of cancer treatments every year. Studies of
compounds that may reverse cachexia and treatments to fight advanced cancers
are under way.
In the 1970s, Joseph
Gold, M.D., a scientist in Syracuse, N.Y., proposed that hydrazine sulfate,
a compound found in rocket fuel, could interrupt the altered glucose
metabolism seen in cancer cachexia. In animal studies, Gold found that the
compound also inhibited tumor growth and sometimes enhanced the anti-cancer
effect of drugs. In preliminary studies in humans, Gold reported some tumor
regression and other subjective improvements in patients. Similarly, Russian
physicians using hydrazine sulfate claimed some patients benefited in
similar ways. In the 1980s, a study of hydrazine sulfate took place at
Harbor-UCLA Medical Center in Torrance, Calif. The trial included 65
patients with advanced lung cancer (nonsmall cell lung cancer) who had not
yet received chemotherapy. Patients were randomized (divided by chance) to
receive either hydrazine sulfate or a placebo in addition to a chemotherapy
regimen (cisplatin, vinblastine, and bleomycin). The study was funded, in
part, by the NCI.
All patients received
nutrition counseling to increase their intake of calorie and nutrients, with
no request to limit alcohol intake and no prohibition of barbiturates. The
particular chemotherapy drugs being used were highly likely to cause nausea
and vomiting, so patients were prescribed anti-emetic drugs to control these
side effects. The anti-emetics were also tranquilizers (benzodiazepines and
Data from the study
suggested that some patients who took hydrazine sulfate -- those who were in
good condition before the study began -- had better survival rates (about a
17-week increase in these terminal patients). All patients on hydrazine
sulfate had greater caloric intake, although that did not translate into a
significant weight gain. Preliminary findings from the study were presented
in early 1987, and the study was published in January 1990.
Based on the findings of
this study, with particular interest in the improvement in survival, NCI
sponsored three large-scale clinical trials of the effects in patients with
two types of advanced cancer -- nonsmall cell lung cancer and colon cancer.
In January 1988, the
Cancer and Leukemia Group B (CALGB), an NCI-sponsored research network
(called a cooperative group), was solicited to conduct a trial. From July
1989 to February 1991, 291 patients with late-stage nonsmall cell lung
cancer who were in good condition (well enough to not be bedridden), were
treated with a chemotherapy regimen of cisplatin and vinblastine and either
hydrazine sulfate or a placebo. Other drugs thought to stimulate appetite
were not permitted. Because the chemotherapy regimen could cause severe
nausea and vomiting in almost all patients, CALGB investigators permitted
the anti-emetic drugs that are also tranquilizers. Barbiturates were not
specifically prohibited, and records show at least one patient received
them. The study ultimately showed no benefit from hydrazine sulfate and
results were published in June 1994.
From May 1990 to October
1992, 243 patients with nonsmall cell lung cancer were enrolled in the
second NCI-funded study of hydrazine sulfate. Headed by the North Central
Cancer Treatment Group (NCCTG), another NCI-cooperative group, the patients
received cisplatin and etoposide as chemotherapy and were randomized to
hydrazine sulfate or a placebo. Again, the chemotherapy regimen used induces
severe nausea and vomiting, so patients were given anti-emetic medication.
These medications included benzodiazepines, pheothiazines, and then newly
available serotonin antagonists. Use of barbiturates and consumption of
alcohol was prohibited.
No differences in
survival, tumor regression, toxicities, or patient quality of life was seen
between the patients receiving hydrazine sulfate and those on placebo. The
study was published in June 1994. An unpublished analysis comparing patients
who received only the newer kind of anti-emetics (serotonin antagonists) to
those taking other anti-emetics, conducted for the GAO investigation, did
not show any survival difference.
From October 1990
through November 1992, NCCTG enrolled 127 patients with metastatic
colorectal cancer into a study of hydrazine sulfate or a placebo. Patients
in this study had been treated with chemotherapy regimens, but their tumors
had not responded. Appetite stimulants, alcohol, barbiturates, and planned
use of tranquilizers were prohibited. Anti-emetic agents were permitted,
because while no chemotherapy was being given, advanced colorectal cancer
patients may experience nausea and vomiting as a symptom of their disease.
Use of such anti-emetics was not widespread in these patients. In this
study, published in June 1994, patients receiving hydrazine sulfate had a
decreased survival compared to patients on placebo.
In 1994, Gold and other
proponents of hydrazine sulfate alleged that NCI compromised these studies
of hydrazine sulfate by permitting patients to have tranquilizers,
barbiturates, and alcohol. He interpreted data from animal studies to
suggest that hydrazine sulfate was incompatible with these drugs. NCI, NCCTG,
and CALGB researchers reviewed the same data and did not interpret it to
show such incompatibility. The study done at UCLA, which had not prohibited
such agents, was the trial that had shown the greatest survival benefit from
hydrazine sulfate. At the request of Congress, the General Accounting Office
undertook an investigation about these allegations, which were found to be
Copies of the GAO report
are available from the U.S. General Accounting Office, Post Office Box 6015,
Gaithersburg, Md. 20884-6015, or call (202) 512-6000. The first copy of the
report is free; additional copies are $2.00 each.
Chlebowski RT, Bulcavage
L, Grosevenor M, et al. Hydrazine sulfate influence on nutritional status
and survival in nonsmall cell lung cancer. Journal of Clinical Oncology
1990; 8(11): 9-15.
Kosty MP, Fleishman SB,
Herndon JE, et al. Cisplatin, vinblastine, and hydrazine sulfate in
advanced, non-small-cell lung cancer: A randomized placebo-controlled,
double-blind phase III study of the Cancer and Leukemia Group B. Journal
of Clinical Oncology 1994; 12(6): 1113-1120.
Loprinzi CL, Goldberg RM,
Su JQ, et al. Placebo-controlled trial of hydrazine sulfate in patients with
newly diagnosed non-small-cell lung cancer. Journal of Clinical Oncology
1994; 12(6): 1126-1129.
Loprinzi CL, Kuross SA,
O’Fallon JR, et al. Randomized placebo-controlled evaluation of hydrazine
sulfate in patients with advanced colorectal cancer. Journal of Clinical
Oncology 1994; 12(6): 1121-1125.