MK-329 is a nonpeptidal, highly specific
cholecystokinin (
CCK) receptor antagonist, with affinity for pancreatic and gallbladder
CCK receptors similar to CCK itself.
MK-329 and its progenitor,
asperlicin, can inhibit the growth of
CCK receptor-positive human
pancreatic cancer in athymic mice. Based on these activities and the ability of
MK-329 to transiently increase food intake and enhance
morphine analgesia in murine models, we conducted an open trial of
MK-329 in 18 patients with advanced
pancreatic cancer in whom the
CCK receptor status of the
tumors was unknown.
Tumor response,
pain control, and nutritional parameters (hunger rating, caloric intake,
body weight, and anthropometrics) were serially assessed. The results of the study failed to demonstrate any impact of
MK-329 on
tumor progression,
pain, or nutrition. Toxicity was mild and limited to
nausea,
vomiting,
diarrhea, and
abdominal cramps, with 17 of 18 patients able to tolerate treatment. While a role for
MK-329 in the management of patients with advanced
pancreatic cancer cannot be supported by the results of this trial, additional studies of this agent in patients with known
CCK receptor-positive
tumors, at escalated doses, and possibly in conjunction with other growth antagonists, appear warranted.