Toxicity and efficacy of isolated lung perfusion with gemcitabine in a rat model of pulmonary metastases.
BACKGROUND
Long-term toxicity and efficacy of isolated left lung perfusion (ILuP) with gemcitabine (GCB) were studied in a rat model of metastatic pulmonary adenocarcinoma.


METHODS



RESULTS
Forty rats were randomized into six groups and administered 160 or 320 mg/kg GCB or buffered starch, received either via intravenous injection (i.v.) or via ILuP. Efficacy experiment: Rats with unilateral metastases had ILuP with 320 mg/kg GCB (maximally tolerated dose administered by ILuP), while rats with bilateral metastases had an i.v. injection of 160 mg/kg GCB (maximally tolerated dose given by i.v.).


RESULTS
TOXICITY experiment: After i.v. treatments, all rats receiving 320 mg/kg GCB died within one week, while rats who had received 160 mg/kg GCB had a survival rate of 60%. After ILuP with 160 mg/kg GCB and 320 mg/kg GCB, survival rates were 83% in both groups. A significant increase in collagen deposits was observed for ILuP with 320 mg/kg GCB compared to rats treated i.v. with 160 mg/kg GCB. Efficacy experiment: Median survival of ILuP rats treated with 320 mg/kg (38 +/- 4 days) was significantly longer compared to i.v. rats treated with 160 mg/kg (27 +/- 2 days; p = 0.02).


CONCLUSIONS
ILuP with GCB prolongs survival in experimental metastatic adenocarcinoma while no major acute or long term toxicity is observed.
Department of Cardiothoracic Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands. bvanputte@yahoo.com
B P
BP
Van Putte
J M H
JM
Hendriks
S
S
Romijn
K
K
De Greef
P E Y
PE
Van Schil
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D010478:Chemotherapy, Cancer, Regional Perfusion; D015179:Colorectal Neoplasms / Q000473:pathology*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D011897:Random Allocation; D051381:Rats; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors; D016896:Treatment Outcome; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D012264:Ribonucleotide Reductases; D000093542:Gemcitabine