PHARMACOLOGY AND ANTITUMOR EFFECTS OF INTRAPORTAL PIRARUBICIN ON EXPERIMENTAL LIVER METASTASES

Early liver metastases have a predominant portal blood supply. Intrapo rtal (i.port.) vein administration of cytotoxics could theoretically a chieve enhanced drug concentrations in tumour cells and be effective a s adjuvant therapy after resection of colorectal carcinoma. Pirarubici n (which has a higher hepatic extraction than doxorubicin) was investi gated on liver metastases of the VX2 rabbit tumour, which were of less than 2 mm in diameter 7 days after cells injection into the portal ve in. To evaluate antitumour activity, 24 rabbits were randomised into t hree groups 7 days after implantation: (a) control, (b) i.v. pirarubic in, (c) i.port. pirarubicin at doses of 2 mg kg-1 in both groups. Port al infusions led to no hematological or hepatic toxicity. Pharmacokine tic parameters showed a significantly reduced systemic exposure after i.port. administration. Fourteen days after treatment, livers and lung s were analysed. The mean number (+/- s.d.) of tumour foci was (a) 8.6 2 (+/- 5.4), (b) 4.62 (+/- 3.2), (c) 2.25 (+- 1.4) (P<0.05 a vs c). Th e mean tumour area was (a) 6.31 (+/- 6.1), (b) 1.31 (+/- 2.2), (c) 0.4 3 (+/- 0.4 cm2) (P<0.05 a vs c) and the percentage (95% C.I.) of rabbi ts with lung metastasis was: (a) 87.5% (47-99%), (b) 75% (35-97%), (c) 12.5% (3-52%) (P<0.02 b vs c). Intraportal pirarubicin seems to be we ll tolerated and more efficient than i.v. administration, particularly in preventing extrahepatic dissemination.