Phase II trial of ZD1694 (Tomudex) in patients with advanced pancreatic cancer.
BACKGROUND
Currently available therapies for advanced pancreatic cancer offer only palliative benefits, and patients with this disease have a poor prognosis. We undertook a phase II trial of ZD1694 (Tomudex), a quinazoline folate analogue that is a potent and selective thymidylate synthase inhibitor, to determine this analogue's efficacy and safety in patients with advanced pancreatic adenocarcinoma.


METHODS
ZD1694, 3.0 mg/m2, was administered to 42 adult patients with pancreatic adenocarcinoma as a 15-minute intravenous infusion every 3 weeks for up to 6 doses. Objective tumor response was assessed every 6 weeks; clinical examinations, adverse event assessments, and clinical laboratory tests were performed every 3 weeks.


RESULTS
ZD1694 produced an overall response rate of 5% (95% confidence limits [CI], 1% to 16%) in the study group. Of 42 patients, 2 (5%) had a partial response, 12 (29%) had stable disease, 21 (50%) had disease progression, and 5 (11%) could not be evaluated for response. Grade 3 vomiting, grades 3 and 4 fever, grade 3 leukopenia, grade 4 thrombocytopenia, and grades 3 and 4 liver function elevations were reported. Toxic effects with ZD1694 were reversible and manageable.


CONCLUSIONS
ZD1694 has an acceptable safety profile but limited activity in patients with advanced pancreatic cancer.
Pazdur
R
R
The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Meropol
N J
NJ
Casper
E S
ES
Fuchs
C
C
Douglass
H O
HO
Vincent
M
M
Abbruzzese
J L
JL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors
D000964:Antimetabolites, Antineoplastic; D004791:Enzyme Inhibitors; D011799:Quinazolines; D013876:Thiophenes; D013940:Thymidylate Synthase; C068874:raltitrexed