A pilot clinical trial of the cholecystokinin receptor antagonist MK-329 in patients with advanced pancreatic cancer.
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.
Abbruzzese
J L
JL
Department of Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Gholson
C F
CF
Daugherty
K
K
Larson
E
E
DuBrow
R
R
Berlin
R
R
Levin
B
B
D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000698:Analgesia; D001570:Benzodiazepinones / Q000009:adverse effects / Q000627:therapeutic use*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D020109:Devazepide; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009747:Nutritional Physiological Phenomena; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D011949:Receptors, Cholecystokinin / Q000187:drug effects*
D001570:Benzodiazepinones; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin; D020109:Devazepide