A phase II trial of perifosine in locally advanced, unresectable, or metastatic pancreatic adenocarcinoma.
BACKGROUND
Perifosine, a heterocyclic alkylphosphocholine signal transduction inhibitor, has activity against multiple cell types in vitro. This is a phase II study to determine activity and toxicity of perifosine in pancreatic adenocarcinoma.


METHODS
Previously untreated patients with locally advanced, unresectable, or metastatic pancreatic adenocarcinoma, performance status Eastern Cooperative Oncology Group 0 or 1, were enrolled. An oral loading dose of 900 mg was followed by 100 mg per day until progression or unacceptable toxicity. Response criteria in solid tumors (RECIST) methodology and a 2-stage design were used. Suspension could occur for inadequate response in the first cohort or for more than 25% grade 3 or greater toxicity.


RESULTS
Ten patients were enrolled. Six received 1 month and 4 received 2 months of treatment. Four discontinued therapy as a result of progression and 2 because of clinical deterioration. Three died during treatment. One patient had stable disease but discontinued therapy as a result of unacceptable adverse events (95% confidence interval: 0.3-45%). There were no objective responses and all patients died of progressive disease. Median overall and progression-free survival was 1.85 months (95% confidence interval: 0.9-2.7) and 1.5 months (95% confidence interval: 0.9-1.9) respectively.


CONCLUSIONS
The study was suspended and subsequently terminated as a result of unacceptable adverse events during the first stage. Perifosine does not appear to be worthy of further study in this group of patients.
Marsh
Robert de W
Rde W
University of Florida, Department of Medicine, Division of Hematology/Oncology, Gainesville, Florida 32610-0277, USA. marshrd@medicine.ufl.edu
Rocha Lima
C M
CM
Levy
D E
DE
Mitchell
E P
EP
Rowland
K M
KM
Benson
A B
AB
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000284:Administration, Oral; D000368:Aged; D000932:Antiemetics / Q000627:therapeutic use; D002648:Child; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018579:Patient Selection; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D016019:Survival Analysis
D000932:Antiemetics; D010767:Phosphorylcholine; C105905:perifosine