BACKGROUND. Currently, immunotherapy with Bacillus Calmette-Guerin (BC
G) is the most effective treatment for superficial bladder carcinoma,
but treatment-related toxicity may limit its use in some patients. Alt
ernative treatments are needed for patients who fail to respond to BCG
immunotherapy. Allium sativum (AS), or garlic, is known to have a bro
ad range of biologic activities, including immune stimulation and repo
rted antitumor activity. For these reasons, the authors conducted a se
ries of experiments designed to explore the possible therapeutic effec
ts 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 10(3) MBT2 cells in 0.1 mt RPMI-1640, administered
subcutaneously into the right thigh, on Day 0 of the experiment. AS w
as 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 t
his model, treatment was initiated 30 days prior to tumor inoculation
and continued for 30 days after tumor inoculation. Animals in all expe
riments were followed for tumor incidence, tumor growth, and survival.
RESULTS. In the initial experiments, subcutaneous AS significantly re
duced tumor volume compared with the saline control (P < 0.05). Unfort
unately, treatment-related death was also observed, requiring reductio
n in the total dose of AS. Animals that received 5 weekly immunization
s of AS (5 mg, 5 mg, 1 mg, 1 mg, and 1 mg; cumulative dose = 13 mg) ha
d significantly reduced tumor incidence, tumor growth, and increased s
urvival when compared with animals that received the saline control. N
o treatment-related deaths were observed with this treatment schedule.
To determine whether systemic AS administration might be effective, o
rally administered AS was tested at doses of 5 mg, 50 mg, and 500 mg p
er 100 mt of drinking water. Mice that received 50 mg oral AS had sign
ificant reductions in tumor volume (P < 0.05) when compared with anima
ls that received the saline control, and mice that received 500 mg ora
l AS had significant reductions in both tumor volume and mortality (P
< 0.05). CONCLUSIONS. The significant antitumor efficacy of subcutaneo
us and oral AS warrants further investigation and suggests that AS may
provide a new and effective form of therapy for transitional cell car
cinoma of the bladder. (C) 1997 American Cancer Society.