Ramirez L H, Munck J N, Bognel C, Zhao Z, Ardouin P, Poupon M F, Gouyette A, Rougier P
Département de Médecine, Institut Gustave-Roussy, Villejuif, France.
Br J Cancer. 1993 Aug;68(2):277-81. doi: 10.1038/bjc.1993.328.
Early liver metastases have a predominant portal blood supply. Intraportal (i.port.) vein administration of cytotoxics could theoretically achieve enhanced drug concentrations in tumour cells and be effective as adjuvant therapy after resection of colorectal carcinoma. Pirarubicin (which has a higher hepatic extraction than doxorubicin) was investigated 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 vein. To evaluate antitumour activity, 24 rabbits were randomised into three groups 7 days after implantation: (a) control, (b) i.v. pirarubicin, (c) i.port. pirarubicin at doses of 2 mg kg-1 in both groups. Portal infusions led to no hematological or hepatic toxicity. Pharmacokinetic parameters showed a significantly reduced systemic exposure after i.port. administration. Fourteen days after treatment, livers and lungs were analysed. The mean number (+/- s.d.) of tumour foci was (a) 8.62 (+/- 5.4), (b) 4.62 (+/- 3.2), (c) 2.25 (+/- 1.4) (P < 0.05 a vs c). The mean tumour area was (a) 6.31 (+/- 6.1), (b) 1.31 (+/- 2.2), (c) 0.43 (+/- 0.4 cm2) (P < 0.05 a vs c) and the percentage (95% C.I.) of rabbits 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 well tolerated and more efficient than i.v. administration, particularly in preventing extrahepatic dissemination.
早期肝转移瘤主要由门静脉供血。理论上，经门静脉内注射细胞毒性药物可提高肿瘤细胞内的药物浓度，并作为结直肠癌切除术后的辅助治疗有效。对VX2兔肿瘤肝转移灶进行了研究，这些转移灶是在将细胞注入门静脉7天后形成的，直径小于2 mm。使用比阿霉素肝摄取率更高的吡柔比星进行研究。为评估抗肿瘤活性，在植入后7天将24只兔子随机分为三组：(a)对照组，(b)静脉注射吡柔比星组，(c)门静脉内注射吡柔比星组，两组剂量均为2 mg·kg-1。门静脉输注未导致血液学或肝脏毒性。药代动力学参数显示门静脉内给药后全身暴露显著降低。治疗14天后，对肝脏和肺进行分析。肿瘤灶的平均数量(±标准差)分别为：(a)8.62(±5.4)，(b)4.62(±3.2)，(c)2.25(±1.4)(a与c相比，P<0.05)。平均肿瘤面积分别为：(a)6.31(±6.1)，(b)1.31(±2.2)，(c)0.43(±0.4 cm2)(a与c相比，P<0.05)，有肺转移的兔子的百分比(95%置信区间)为：(a)87.5%(47-99%)，(b)75%(35-97%)，(c)12.5%(3-52%)(b与c相比，P<0.02)。门静脉内注射吡柔比星似乎耐受性良好，且比静脉注射更有效，尤其是在预防肝外播散方面。
