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.
Van Putte
B P
BP
Department of Cardiothoracic Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands. bvanputte@yahoo.com
Hendriks
J M H
JM
Romijn
S
S
De Greef
K
K
Van Schil
P E Y
PE
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