FROM:
Cancer 1997 (May); 79: 1987–1994
Riggs DR, DeHaven JI, Lamm DL
Department of Urology,
West Virginia University School of Medicine,
Morgantown 26506, USA
BACKGROUND: Currently, immunotherapy with Bacillus
Calmette-Guerin (BCG) is the most effective treatment for
superficial bladder carcinoma, but treatment-related toxicity may
limit its use in some patients. Alternative treatments are needed
for patients who fail to respond to BCG immunotherapy. Allium
sativum (AS), or garlic, is known to have a broad range of
biologic activities, including immune stimulation and reported
antitumor activity. For these reasons the authors conducted a
series of experiments designed to explore the possible
therapeutic effects of AS in the MBT2 murine bladder carcinoma
model.
METHODS: C3H/HeN mice were randomized prior to
initiation of each experimental protocol. Mice received 1 x 103
MBT2 ceus in 0.1 mL RPMI-1640, administered subcutaneously into
the right thigh, on Day 0 of the experiment. AS was injected at
the site of tumor transplantation on Day 1 and at 2- to 7-day
intervals up to Day 28. To evaluate the effects of oral AS in
this model, treatment was initiated 30 days prior to tumor
inoculation and continued for 30 days after tumor inoculation.
Animals in all experiments were followed for tumor incidence,
tumor growth, and survival.
RESULTS: In the initial experiments, subcutaneous AS
significantly reduced tumor volume compared with the saline
control (P < 0.05). Unfortunately, treatment-related death was
also observed, requiring reduction in the total dose of AS.
Animals that received 5 weekly immunizations of AS (5 mg, 5 mg, 1
mg, I mg, and I mg; cumulative dose = 13 mg) had significantly
reduced tumor incidence, tumor growth, and increased survival
when compared with animals that received the saline control. No
treatment-related deaths were observed with this treatment
schedule. To determine whether systemic AS administration might
be effective, orally administered AS was tested at doses of 5 mg,
50 mg, and 500 mg per 100 mL of drinking water. Mice that
received 50 mg oral AS had significant reductions in tumor volume
(P < 0.05) when compared with animals that received the saline
control, and mice that received 500 mg oral AS had significant
reductions in both tumor volume and mortality (P < 0.05).
CONCLUSIONS: The significant antitumor efficacy of
subcutaneous and oral AS warrants further investigation and
suggests that AS may provide a new and effective form of therapy
for transitional cell carcinoma of the bladder.