Daunorubicin and daunorubicinol tissue concentrations in gastric cancer patients after local administration of a liposomal preparation.
BACKGROUND
In order to study a model that maximizes gastric cancer tissue and lymph node exposure to antineoplastic drugs while simultaneously reducing their systemic bioavailability, we implemented a preliminary investigation of the disposition of a daunorubicin liposomal preparation (D) in gastric cancer patients by means of gastric submucosa injection.


METHODS
After a dose finding study, 12 patients (candidates for gastric resection because of gastric cancer) were studied by administering two doses of 50 mg of D (the highest tolerated dose) 1 week before surgery.


RESULTS
Mean tissue concentrations at surgery were higher in cancer, normal non-injected peritumoral mucosa, and lymph node tissues than in serum or urine, in which there were only trace concentrations. While epigastric pain and histological modifications (inflammation and thickening of the gastric layers) were manifest in patients treated with 75 mg doses in the dose finding session, no clinical signs or symptoms of toxicity were recorded in those administered with 50 mg doses.


CONCLUSIONS
Local administration of D may allow it to reach high concentrations in normal non-injected peritumoral mucosa, and lymph nodes, while simultaneously avoiding significant systemic exposure and toxicity. This procedure could merit further investigation, in view of a possible use of anthracyclines against metastatic diffusion through the lymphatic system in gastric cancer patients who are candidates for gastric resection.
Furlanut
M
M
Institute of Clinical Pharmacology and Toxicology, DPMSC, University of Udine, Italy. mario.furlanut@med.uniud.it
de Manzoni
G
G
Pasini
F
F
Tasselli
S
S
Tomezzoli
A
A
Poz
D
D
Franceschi
L
L
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003630:Daunorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005753:Gastric Mucosa; D005773:Gastroscopy; D006801:Humans; D007267:Injections; D015552:Injections, Intralesional; D008081:Liposomes; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000378:metabolism; D014018:Tissue Distribution
D000903:Antibiotics, Antineoplastic; D008081:Liposomes; C000847:daunorubicinol; D003630:Daunorubicin